354 research outputs found

    Vermeerdering tulp in weefselkweek: een werkbaar protocol

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    De veredeling van tulp gaat traag door de lange generatietijd en door langzame vermeerdering op het veld. Een veredelingsprogramma van tulp duurt al snel 25 jaar. Dit kan aanzienlijk verkort worden door vermeerdering in weefselkweek. Er is nu een werkbaar protoco

    Qualitative Evaluation of Common Quantitative Metrics for Clinical Acceptance of Automatic Segmentation:a Case Study on Heart Contouring from CT Images by Deep Learning Algorithms

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    Organs-at-risk contouring is time consuming and labour intensive. Automation by deep learning algorithms would decrease the workload of radiotherapists and technicians considerably. However, the variety of metrics used for the evaluation of deep learning algorithms make the results of many papers difficult to interpret and compare. In this paper, a qualitative evaluation is done on five established metrics to assess whether their values correlate with clinical usability. A total of 377 CT volumes with heart delineations were randomly selected for training and evaluation. A deep learning algorithm was used to predict the contours of the heart. A total of 101 CT slices from the validation set with the predicted contours were shown to three experienced radiologists. They examined each slice independently whether they would accept or adjust the prediction and if there were (small) mistakes. For each slice, the scores of this qualitative evaluation were then compared with the Sørensen-Dice coefficient (DC), the Hausdorff distance (HD), pixel-wise accuracy, sensitivity and precision. The statistical analysis of the qualitative evaluation and metrics showed a significant correlation. Of the slices with a DC over 0.96 (N = 20) or a 95% HD under 5 voxels (N = 25), no slices were rejected by the readers. Contours with lower DC or higher HD were seen in both rejected and accepted contours. Qualitative evaluation shows that it is difficult to use common quantification metrics as indicator for use in clinic. We might need to change the reporting of quantitative metrics to better reflect clinical acceptance

    Breaking the cycle of loneliness?: Psychological effects of a friendship enrichment program for older women

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    Contains fulltext : 56871.pdf (publisher's version ) (Closed access)The present study examines effects of participation in the friendship enrichment program, an intervention that is designed to stimulate improvement in friendship, self-esteem and subjective well-being, as well as reduction in loneliness among older women. The intervention group was compared to a control group of women who were interested in the program or in improving their friendships. All respondents had been studied at three points in time: at a baseline, prior to the program; three months later, and 9-10 months after baseline. The results indicate that the program was successful in attracting lonely older women who were willing to work on their friendships. Many participants reported improvement in the quantity and quality of their friendships. The program was moderately successful in stimulating improvement in subjective well-being and awareness of the need for an active stance toward achieving goals in social relations, especially in friendship. Loneliness among the participants was reduced, but it also declined in the control group, and both groups continued to experience loneliness. One conclusion is that an effective intervention to help older women reduce their loneliness should be multi-dimensional focusing not only on friendship but also on other personal and situational factors contributing to loneliness.9 p

    Altered intercellular communication in lung fibroblast cultures from patients with idiopathic pulmonary fibrosis

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    RATIONALE: Gap junctions are membrane channels formed by an array of connexins which links adjacent cells realizing an electro- metabolic synapse. Connexin-mediated communication is crucial in the regulation of cell growth, differentiation, and development. The activation and proliferation of phenotypically altered fibroblasts are central events in the pathogenesis of idiopathic pulmonary fibrosis. We sought to evaluate the role of connexin-43, the most abundant gap-junction subunit in the human lung, in the pathogenesis of this condition. METHODS: We investigated the transcription and protein expression of connexin-43 and the gap-junctional intercellular communication (GJIC) in 5 primary lung fibroblast lines derived from normal subjects (NF) and from 3 histologically proven IPF patients (FF). RESULTS: Here we show that connexin-43 mRNA was significantly reduced in FF as demonstrated by standard and quantitative RT-PCR. GJIC was functionally evaluated by means of flow-cytometry. In order to demonstrate that dye spreading was taking place through gap junctions, we used carbenoxolone as a pharmacological gap-junction blocker. Carbenoxolone specifically blocked GJIC in our system in a concentration dependent manner. FF showed a significantly reduced homologous GJIC compared to NF. Similarly, GJIC was significantly impaired in FF when a heterologous NF line was used as dye donor, suggesting a complete defect in GJIC of FF. CONCLUSION: These results suggest a novel alteration in primary lung fibroblasts from IPF patients. The reduced Cx43 expression and the associated alteration in cell-to-cell communication may justify some of the known pathological characteristic of this devastating disease that still represents a challenge to the medical practice

    Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations

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    Background: The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. Methods: In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen. Results: Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73–88%) (four patients with clinical complete response declined surgery). Twenty–four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05–1.03, P=0.055). Conclusions: This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss

    The Infrared Light Curve of SN 2011fe in M101 and the Distance to M101

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    We present near infra-red light curves of supernova (SN) 2011fe in M101, including 34 epochs in H band starting fourteen days before maximum brightness in the B-band. The light curve data were obtained with the WIYN High-Resolution Infrared Camera (WHIRC). When the data are calibrated using templates of other Type Ia SNe, we derive an apparent H-band magnitude at the epoch of B-band maximum of 10.85 \pm 0.04. This implies a distance modulus for M101 that ranges from 28.86 to 29.17 mag, depending on which absolute calibration for Type Ia SNe is used.Comment: 9 pages, 3 figures, emulateapj style, accepted for publication in The Astrophysical Journa

    Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

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    Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL

    RNA localization in neurite morphogenesis and synaptic regulation: current evidence and novel approaches

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    It is now generally accepted that RNA localization in the central nervous system conveys important roles both during development and in the adult brain. Of special interest is protein synthesis located at the synapse, as this potentially confers selective synaptic modification and has been implicated in the establishment of memories. However, the underlying molecular events are largely unknown. In this review, we will first discuss novel findings that highlight the role of RNA localization in neurons. We will focus on the role of RNA localization in neurotrophin signaling, axon outgrowth, dendrite and dendritic spine morphogenesis as well as in synaptic plasticity. Second, we will briefly present recent work on the role of microRNAs in translational control in dendrites and its implications for learning and memory. Finally, we discuss recent approaches to visualize RNAs in living cells and their employment for studying RNA trafficking in neurons
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