Convective regularization for optical flow

We argue that the time derivative in a fixed coordinate frame may not be the most appropriate measure of time regularity of an optical flow field. Instead, for a given velocity field $v$ we consider the convective acceleration $v_t + \nabla v v$ which describes the acceleration of objects moving according to $v$. Consequently we investigate the suitability of the nonconvex functional $\|v_t + \nabla v v\|^2_{L^2}$ as a regularization term for optical flow. We demonstrate that this term acts as both a spatial and a temporal regularizer and has an intrinsic edge-preserving property. We incorporate it into a contrast invariant and time-regularized variant of the Horn-Schunck functional, prove existence of minimizers and verify experimentally that it addresses some of the problems of basic quadratic models. For the minimization we use an iterative scheme that approximates the original nonlinear problem with a sequence of linear ones. We believe that the convective acceleration may be gainfully introduced in a variety of optical flow models

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Review of Economic Submissions to NICE Medical Technologies Evaluation Programme

The economic evaluation of medical devices is increasingly used to inform decision making on adopting new or novel technologies; however, challenges are inevitable due to the unique characteristics of devices. Cost-consequence analyses are recommended and employed by the English National Institute for Health and Care Excellence (NICE) Medical Technologies Evaluation Programme (MTEP) to help address these challenges. The aim of this work was to review the critiques raised for previous MTEP submissions and explore if there were common problems across submissions. We reviewed a sample of 12 economic submissions to MTEP representing 50 % of 24 sets of guidance issued to July 2015. For each submission, we reviewed the External Assessment Centre's (EAC) report and the guidance document produced by NICE. We identified the main problems raised by the EAC's assessments and the committee's considerations for each submission, and explored strategies for improvement. We found that the identification and measurement of costs and consequences are the main shortcomings within economic submissions to MTEP. Together, these shortcomings accounted for 42 % of criticisms by the EACs among the reviewed submissions. In certain circumstances problems with these shortcomings may be unavoidable, for example, if there is a limited evidence base for the device being appraised. Nevertheless, strategies can often be adopted to improve submissions, including the use of more appropriate time horizons, whilst cost and resource use information should be taken, where possible, from nationally representative sources

Unravelling the genome-wide contributions of specific 2-alkyl-4-quinolones and PqsE to quorum sensing in Pseudomonas aeruginosa

The pqs quorum sensing (QS) system is crucial for Pseudomonas aeruginosa virulence both in vitro and in animal models of infection and is considered an ideal target for the development of anti-virulence agents. However, the precise role played by each individual component of this complex QS circuit in the control of virulence remains to be elucidated. Key components of the pqs QS system are 2-heptyl-4-hydroxyquinoline (HHQ), 2-heptyl-3-hydroxy-4-quinolone (PQS), 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), the transcriptional regulator PqsR and the PQS-effector element PqsE. To define the individual contribution of each of these components to QS-mediated regulation, transcriptomic analyses were performed and validated on engineered P. aeruginosa strains in which the biosynthesis of 2-alkyl 4-quinolones (AQs) and expression of pqsE and pqsR have been uncoupled, facilitating the identification of the genes controlled by individual pqs system components. The results obtained demonstrate that i) the PQS biosynthetic precursor HHQ triggers a PqsR-dependent positive feedback loop that leads to the increased expression of only the pqsABCDE operon, ii) PqsE is involved in the regulation of diverse genes coding for key virulence determinants and biofilm development, iii) PQS promotes AQ biosynthesis, the expression of genes involved in the iron-starvation response and virulence factor production via PqsR-dependent and PqsR-independent pathways, and iv) HQNO does not influence transcription and hence does not function as a QS signal molecule. Overall this work has facilitated identification of the specific regulons controlled by individual pqs system components and uncovered the ability of PQS to contribute to gene regulation independent of both its ability to activate PqsR and to induce the iron-starvation response

Spatial Heterogeneity of Autoinducer Regulation Systems

Autoinducer signals enable coordinated behaviour of bacterial populations, a phenomenon originally described as quorum sensing. Autoinducer systems are often controlled by environmental substances as nutrients or secondary metabolites (signals) from neighbouring organisms. In cell aggregates and biofilms gradients of signals and environmental substances emerge. Mathematical modelling is used to analyse the functioning of the system. We find that the autoinducer regulation network generates spatially heterogeneous behaviour, up to a kind of multicellularity-like division of work, especially under nutrient-controlled conditions. A hybrid push/pull concept is proposed to explain the ecological function. The analysis allows to explain hitherto seemingly contradicting experimental findings

Distant Metastasis After Chemoradiation and Image Guided Adaptive Brachytherapy in Locally Advanced Cervical Cancer

Purpose: This study aimed to assess patterns and risks of distant metastasis (DM) in patients with cervical cancer treated with chemoradiation therapy and MR-image guided adaptive brachytherapy (IGABT) and to explore a potential dose-effect relationship of concomitant cisplatin. Methods and Materials: Data were derived from EMBRACE I, an international, prospective, and multicenter cohort study conducted at 24 centers across Europe, Asia, and North America from July 30, 2008, to December 29, 2015. The study included 1416 patients with biopsy-confirmed cervical cancer (International Federation of Gynecology and Obstetrics [FIGO2009] stage IB-IVA or stage IVB limited to paraaortic lymph nodes below the L1/L2 interspace). Treatment involved external beam radiation therapy (45-50.4 Gy), weekly cisplatin (40 mg/m², 30 mg/m², or paused), and IGABT. DM was defined as extra-pelvic recurrence excluding paraaortic nodes. Results: The analysis included 1318 patients with a median age of 49 years and a median follow-up of 52 months. The 5-year cumulative incidence of DM was 14%, with the lungs (26%), mediastinal lymph nodes (15%), and bones (10%) identified as the most common metastatic sites. Key risk factors for DM included nonsquamous histology (HR, 1.89; 95% CI, 1.30-2.75), nodal involvement at diagnosis (pelvic-only nodes: HR, 1.56; 95% CI, 1.07-2.26; paraaortic nodes: HR, 3.15; 95% CI, 1.93-5.16), and large target volume at brachytherapy (HR, 1.93; 95% CI, 1.21-3.08). Patients receiving fewer than 4 cycles of chemotherapy demonstrated a significantly higher risk of DM (HR, 1.52; 95% CI, 1.08-2.13). Conclusion: DM is a substantial burden in patients with locally advanced cervical cancer, with the lungs, distant lymph nodes, and bones being the most frequent sites. Risk factors such as nonsquamous histology, nodal involvement, and large target volumes at brachytherapy are critical considerations for identifying high-risk patients in future studies. These findings highlight the need for tailored strategies to mitigate DM in this patient population.</p

Genes That Influence Swarming Motility and Biofilm Formation in Variovorax paradoxus EPS

Variovorax paradoxus is an aerobic soil bacterium associated with important biodegradative processes in nature. We use V. paradoxus EPS to study multicellular behaviors on surfaces.We recovered flanking sequence from 123 clones in a Tn5 mutant library, with insertions in 29 different genes, selected based on observed surface behavior phenotypes. We identified three genes, Varpa_4665, Varpa_4680, and Varpa_5900, for further examination. These genes were cloned into pBBR1MCS2 and used to complement the insertion mutants. We also analyzed expression of Varpa_4680 and Varpa_5900 under different growth conditions by qPCR.The 29 genes we identified had diverse predicted functions, many in exopolysaccharide synthesis. Varpa_4680, the most commonly recovered insertion site, encodes a putative N-acetyl-L-fucosamine transferase similar to WbuB. Expression of this gene in trans complemented the mutant fully. Several unique insertions were identified in Varpa_5900, which is one of three predicted pilY1 homologs in the EPS genome. No insertions in the two other putative pilY1 homologs present in the genome were identified. Expression of Varpa_5900 altered the structure of the wild type swarm, as did disruption of the chromosomal gene. The swarming phenotype was complemented by expression of Varpa_5900 from a plasmid, but biofilm formation was not restored. Both Varpa_4680 and Varpa_5900 transcripts were downregulated in biofilms and upregulated during swarming when compared to log phase culture. We identified a putative two component system (Varpa_4664-4665) encoding a response regulator (shkR) and a sensor histidine kinase (shkS), respectively. Biofilm formation increased and swarming was strongly delayed in the Varpa_4665 (shkS) mutant. Complementation of shkS restored the biofilm phenotype but swarming was still delayed. Expression of shkR in trans suppressed biofilm formation in either genetic background, and partially restored swarming in the mutant.The data presented here point to complex regulation of these surface behaviors

Fungal associates of the lodgepole pine beetle, Dendroctonus murrayanae

Bark beetles are well known vectors of ophiostomatoid fungi including species of Ophiostoma, Grosmannia and Ceratocystis. In this study, the most common ophiostomatoid fungi associated with the lodgepole pine beetle, Dendroctonus murrayanae, were characterized. Pre-emergent and post-attack adult beetles were collected from lodgepole pines at four sites in British Columbia, Canada. Fungi were isolated from these beetles and identified using a combination of morphology and DNA sequence comparisons of five gene regions. In all four populations, Grosmannia aurea was the most common associate (74–100% of all beetles) followed closely by Ophiostoma abietinum (29–75%). Other fungi isolated, in order of their relative prevalence with individual beetles were an undescribed Leptographium sp. (0–13%), Ophiostoma ips (0–15%), Ophiostoma piliferum (0–11%), a Pesotum sp. (0–11%) and Ophiostoma floccosum (0–1%). Comparisons of the DNA sequences of Leptographium strains isolated in this study, with ex-type isolates of G. aurea, Grosmannia robusta, Leptographium longiclavatum, and Leptographium terebrantis, as well as with sequences from GenBank, revealed a novel lineage within the Grosmannia clavigera complex. This lineage included some of the D. murrayane isolates as well as several isolates from previous studies referred to as L. terebrantis. However, the monophyly of this lineage is not well supported and a more comprehensive study will be needed to resolve its taxonomic status as one or more novel taxa.National Science Foundation grant OISE-0434171 awarded to DLS, Natural Resources Canada, Canadian Forest Service Mountain Pine Beetle Initiative Grant to ALC, members of the Tree Co-operative Programme, the THRIP initiative of the Department of Trade and Industry, South Africa

A mathematical model of quorum sensing regulated EPS production in biofilm communities

<p>Abstract</p> <p>Background</p> <p>Biofilms are microbial communities encased in a layer of extracellular polymeric substances (EPS). The EPS matrix provides several functional purposes for the biofilm, such as protecting bacteria from environmental stresses, and providing mechanical stability. Quorum sensing is a cell-cell communication mechanism used by several bacterial taxa to coordinate gene expression and behaviour in groups, based on population densities.</p> <p>Model</p> <p>We mathematically model quorum sensing and EPS production in a growing biofilm under various environmental conditions, to study how a developing biofilm impacts quorum sensing, and conversely, how a biofilm is affected by quorum sensing-regulated EPS production. We investigate circumstances when using quorum-sensing regulated EPS production is a beneficial strategy for biofilm cells.</p> <p>Results</p> <p>We find that biofilms that use quorum sensing to induce increased EPS production do not obtain the high cell populations of low-EPS producers, but can rapidly increase their volume to parallel high-EPS producers. Quorum sensing-induced EPS production allows a biofilm to switch behaviours, from a colonization mode (with an optimized growth rate), to a protection mode.</p> <p>Conclusions</p> <p>A biofilm will benefit from using quorum sensing-induced EPS production if bacteria cells have the objective of acquiring a thick, protective layer of EPS, or if they wish to clog their environment with biomass as a means of securing nutrient supply and outcompeting other colonies in the channel, of their own or a different species.</p