Decoy engineering: The next step in resistance breeding.

The recent finding that decoy engineering can expand the recognition specificity of a plant immune receptor opens a wealth of opportunities for resistance breeding. In this Spotlight we discuss which factors should be considered to successfully translate decoy engineering into crop species

The praxis of ‘alignment seeking’ in project work

Alignment seeking is the process of reaching agreement on what needs to be done and on the process that should be followed to complete the activity. This empirical study extends the scope of the current project-as-practice literature by providing descriptions of how project managers actually achieve alignment. Photographs taken by the research participants are used to trigger discussion in semi-structured interviews that explore the praxis of alignment seeking in project work. The practices found to enable alignment seeking include: creating a vision; storytelling; seeding ideas; identifying and using personal drivers, and appealing to stakeholders and team members' sense of a ‘higher good’. This paper highlights how alignment seeking can be achieved ‘in practice’ by project managers

A Heideggerian paradigm for project management: breaking free of the disciplinary matrix and its Cartesian ontology

The purpose of this paper is to identify the new insights that emerge if key concepts in Heidegger's magnum opus Being and Time are applied to the phenomena of projects and their management. A theoretical approach is adopted with an introduction being provided to key Being and Time concepts, followed by the application of these concepts to the phenomena of projects and their management. A particular focus is on the relevance of Heidegger's ontology in underpinning the exploration of the 'lived experience' of project management and the disclosing of the actuality of project phenomena. It is found that key concepts in Heidegger's Being and Time (such as temporality, modes of being, being-in-the-world, dealing and the they) provide insights into various aspects of project management. The significance of such findings is demonstrated through a reconceptualisation of projects; and differentiation between, and reconceptualisation of project management versus project managing

Ollivier-Ricci curvature convergence in random geometric graphs

Connections between continuous and discrete worlds tend to be elusive. One example is curvature. Even though there exist numerous nonequivalent definitions of graph curvature, none is rigorously known to converge in any limit to any traditional definition of curvature of a Riemannian manifold. Here we show that Ollivier curvature of random geometric graphs in any Riemannian manifold converges in the continuum limit to Ricci curvature of the underlying manifold. This result establishes the first rigorous link between a definition of curvature applicable to random graphs and a traditional definition of curvature of smooth space

Extent of resection of peritumoral diffusion tensor imaging-detected abnormality as a predictor of survival in adult glioblastoma patients

OBJECTIVE Diffusion tensor imaging (DTI) has been shown to detect tumor invasion in glioblastoma patients and has been applied in surgical planning. However, the clinical value of the extent of resection based on DTI is unclear. Therefore, the correlation between the extent of resection of DTI abnormalities and patients' outcome was retrospectively reviewed.METHODS A review was conducted of 31 patients with newly diagnosed supratentorial glioblastoma who underwent standard 5-aminolevulinic-acid aided surgery with the aim of maximal resection of the enhancing tumor component. All patients underwent presurgical MRI, including volumetric postcontrast T1-weighted imaging, DTI, and FLAIR. Postsurgical anatomical MR images were obtained within 72 hours of resection. The diffusion tensor was split into an isotropic (p) and anisotropic (q) component. The extent of resection was measured for the abnormal area on the p, q, FLAIR, and postcontrast T1-weighted images. Data were analyzed in relation to patients' outcome using univariate and multivariate Cox regression models controlling for possible confounding factors including age, O-6-methylguanine-DNA-methyltransferase methylation status, and isocitrate dehydrogenase-1 mutation.RESULTS Complete resection of the enhanced tumor shown on the postcontrast II-weighted images was achieved in 24 of 31 patients (77%). The mean extent of resection of the abnormal p, q, and FLAIR areas was 57%, 83%, and 59%, respectively. Increased resection of the abnormal p and q areas correlated positively with progression-free survival (p = 0.009 and p = 0.006, respectively). Additionally, a larger, residual, abnormal q volume predicted significantly shorter time to progression (p = 0.008). More extensive resection of the abnormal q and contrast-enhanced area improved overall survival (p = 0.041 and 0.050, respectively).CONCLUSIONS Longer progression-free survival and overall survival were seen in glioblastoma patients in whom more DTI-documented abnormality was resected, which was previously shown to represent infiltrative tumor. This highlights the potential usefulness and the importance of an extended resection based on DTI-derived maps.</p

Posttreatment periresectional ADC in GBM

BACKGROUND: Although targeted by radiotherapy, recurrence in glioblastoma occurs mainly periresectionally owing to tumor infiltration. An increase in the apparent diffusion coefficient (ADC) has been shown in the large high-T2 area on magnetic resonance imaging posttreatment; however, until now ADC has not been investigated directly in the more relevant periresectional area. METHODS: Histogram analysis was used to assess periresectional ADC values in patients with glioblastoma postradiotherapy versus preradiotherapy. Periresectional ADC values starting at 0-5 mm in 5-mm increments up to 20-25 mm were extracted and compared using 2-way repeated-measurements analysis of variance. RESULTS: Mean ADC values directly adjacent to the resection area (0-5 mm) were significantly higher postradiotherapy compared with preradiotherapy (P = .017). ADC values in the 0- to 5-mm region were also higher than those in 5- to 10-, 10- to 15-, and 15- to 20-mm regions (P < .05). Regional standard deviations in ADC values were higher postradiotherapy compared with preradiotherapy for the 0- to 5-mm region up to the 15- to 20-mm region, inclusive (P < .05); however, Cox regression analysis showed no survival benefits from the increased ADC in the 0- to 5-mm region postradiotherapy. CONCLUSIONS: Increased ADC values, representing a decrease in infiltrative tumor load, were demonstrated in a limited direct periresectional area. This finding adds to previous studies evaluating ADC response in the larger high-T2 area in relation to survival.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.wneu.2016.04.12

A Neural Network Approach to Identify the Peritumoral Invasive Areas in Glioblastoma Patients by Using MR Radiomics

The challenge in the treatment of glioblastoma is the failure to identify the cancer invasive area outside the contrast-enhancing tumour which leads to the high local progression rate. Our study aims to identify its progression from the preoperative MR radiomics. 57 newly diagnosed cerebral glioblastoma patients were included. All patients received 5-aminolevulinic acid (5-ALA) fluorescence guidance surgery and postoperative temozolomide concomitant chemoradiotherapy. Preoperative 3 T MRI data including structure MR, perfusion MR, and DTI were obtained. Voxel-based radiomics features extracted from 37 patients were used in the convolutional neural network to train and as internal validation. Another 20 patients of the cohort were tested blindly as external validation. Our results showed that the peritumoural progression areas had higher signal intensity in FLAIR (p = 0.02), rCBV (p = 0.038), and T1C (p = 0.0004), and lower intensity in ADC (p = 0.029) and DTI-p (p = 0.001) compared to non-progression area. The identification of the peritumoural progression area was done by using a supervised convolutional neural network. There was an overall accuracy of 92.6% in the training set and 78.5% in the validation set. Multimodal MR radiomics can demonstrate distinct characteristics in areas of potential progression on preoperative MRI.</p

Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type glioblastoma

PURPOSE: (11)C-Methionine ((11)C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for survival correlation in patients with IDH wild type glioblastomas. METHODS: Thirteen IDH wild type glioblastoma patients underwent preoperative (11)C-MET PET. Both SUV-based parameters and volume-based parameters were calculated for each lesion. Kaplan-Meier curves with log-rank testing and Cox regression analysis were used for correlation between PET parameters and overall survival. RESULTS: Median overall survival for the entire cohort was 393 days. MTV (HR 1.136, p = 0.007) and TLMM (HR 1.022, p = 0.030) were inversely correlated with overall survival. SUV-based (11)C-MET PET parameters did not show a correlation with survival. In a paired analysis with other clinical parameters including age and radiotherapy dose, MTV and TLMM were found to be independent factors. CONCLUSIONS: MTV and TLMM, and not SUV, significantly correlate with overall survival in patients with IDH wild type glioblastomas. The incorporation of volume-based (11)C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population

On the evolution of decoys in plant immune systems

The Guard-Guardee model for plant immunity describes how resistance proteins (guards) in host cells monitor host target proteins (guardees) that are manipulated by pathogen effector proteins. A recently suggested extension of this model includes decoys, which are duplicated copies of guardee proteins, and which have the sole function to attract the effector and, when modified by the effector, trigger the plant immune response. Here we present a proof-of-principle model for the functioning of decoys in plant immunity, quantitatively developing this experimentally-derived concept. Our model links the basic cellular chemistry to the outcomes of pathogen infection and resulting fitness costs for the host. In particular, the model allows identification of conditions under which it is optimal for decoys to act as triggers for the plant immune response, and of conditions under which it is optimal for decoys to act as sinks that bind the pathogen effectors but do not trigger an immune response.Comment: 15 pages, 6 figure