SISS-MCO:large scale sparsity-induced spot selection for fast and fully-automated robust multi-criteria optimisation of proton plans

Objective. Intensity modulated proton therapy (IMPT) is an emerging treatment modality for cancer. However, treatment planning for IMPT is labour-intensive and time-consuming. We have developed a novel approach for multi-criteria optimisation (MCO) of robust IMPT plans (SISS-MCO) that is fully automated and fast, and we compare it for head and neck, cervix, and prostate tumours to a previously published method for automated robust MCO (IPBR-MCO, van de Water 2013). Approach. In both auto-planning approaches, the applied automated MCO of spot weights was performed with wish-list driven prioritised optimisation (Breedveld 2012). In SISS-MCO, spot weight MCO was applied once for every patient after sparsity-induced spot selection (SISS) for pre-selection of the most relevant spots from a large input set of candidate spots. IPBR-MCO had several iterations of spot re-sampling, each followed by MCO of the weights of the current spots. Main results. Compared to the published IPBR-MCO, the novel SISS-MCO resulted in similar or slightly superior plan quality. Optimisation times were reduced by a factor of 6 i.e. from 287 to 47 min. Numbers of spots and energy layers in the final plans were similar. Significance. The novel SISS-MCO automatically generated high-quality robust IMPT plans. Compared to a published algorithm for automated robust IMPT planning, optimisation times were reduced on average by a factor of 6. Moreover, SISS-MCO is a large scale approach; this enables optimisation of more complex wish-lists, and novel research opportunities in proton therapy.</p

SISS-MCO:large scale sparsity-induced spot selection for fast and fully-automated robust multi-criteria optimisation of proton plans

Objective. Intensity modulated proton therapy (IMPT) is an emerging treatment modality for cancer. However, treatment planning for IMPT is labour-intensive and time-consuming. We have developed a novel approach for multi-criteria optimisation (MCO) of robust IMPT plans (SISS-MCO) that is fully automated and fast, and we compare it for head and neck, cervix, and prostate tumours to a previously published method for automated robust MCO (IPBR-MCO, van de Water 2013). Approach. In both auto-planning approaches, the applied automated MCO of spot weights was performed with wish-list driven prioritised optimisation (Breedveld 2012). In SISS-MCO, spot weight MCO was applied once for every patient after sparsity-induced spot selection (SISS) for pre-selection of the most relevant spots from a large input set of candidate spots. IPBR-MCO had several iterations of spot re-sampling, each followed by MCO of the weights of the current spots. Main results. Compared to the published IPBR-MCO, the novel SISS-MCO resulted in similar or slightly superior plan quality. Optimisation times were reduced by a factor of 6 i.e. from 287 to 47 min. Numbers of spots and energy layers in the final plans were similar. Significance. The novel SISS-MCO automatically generated high-quality robust IMPT plans. Compared to a published algorithm for automated robust IMPT planning, optimisation times were reduced on average by a factor of 6. Moreover, SISS-MCO is a large scale approach; this enables optimisation of more complex wish-lists, and novel research opportunities in proton therapy.</p

Reducing the lateral dose penumbra in IMPT by incorporating transmission pencil beams

Objective: In intensity-modulated proton therapy (IMPT), Bragg peaks result in steep distal dose fall-offs, while the lateral IMPT dose fall-off is often less steep than in photon therapy. High-energy pristine transmission (‘shoot through’) pencil beams have no Bragg peak in the patient, but show a sharp lateral penumbra at the target level. We investigated whether combining Bragg peaks with Transmission pencil beams (‘IMPT&amp;TPB’) could improve head-and-neck plans by exploiting the steep lateral dose fall-off of transmission pencil beams. Approach: Our system for automated multi-criteria IMPT plan optimisation was extended for combined optimisation of BPs and TPBs. The system generates for each patient a Pareto-optimal plan using a generic ‘wish-list’ with prioritised planning objectives and hard constraints. For eight nasopharynx cancer patients (NPC) and eight oropharynx cancer (OPC) patients, the IMPT&amp;TPB plan was compared to the competing conventional IMPT plan with only Bragg peaks, which was generated with the same optimiser, but without transmission pencil beams. Main results: Clinical OAR and target constraints were met in all plans. By allowing transmission pencil beams in the optimisation, on average 14 of the 25 investigated OAR plan parameters significantly improved for NPC, and 9 of the 17 for OPC, while only one OPC parameter showed small but significant deterioration. Non-significant differences were found in the remaining parameters. In NPC, cochlea Dmean reduced by up to 17.5 Gy and optic nerve D2% by up to 11.1 Gy. Conclusion: Compared to IMPT, IMPT&amp;TPB resulted in comparable target coverage with overall superior OAR sparing, the latter originating from steeper dose fall-offs close to OARs.</p

The impact of participation restrictions on everyday life in long-term colorectal cancer survivors in the EnCoRe study:A mixed-method study

Purpose: Knowledge about long-term colorectal cancer (CRC) or treatment related health and functioning problems and on its impact on participation of CRC survivors in domestic life and in society is limited. We aimed to explore the nature and impact of cancer (treatment) related participation restrictions on everyday life of long-term CRC survivors, their current satisfaction with participation, and associations of health and functioning problems with participation satisfaction, using the International Classification of Functioning, Disability and Health (ICF) to comprehensively study participation.Method: Mixed-method study in 2-10 years post-diagnosis stage I-III CRC survivors (n = 151) from the cross-sectional part of the EnCoRe study. Participation restrictions were explored by semi-structured interviews in a subsample reporting participation restrictions (n = 10). Role functioning (SF36-Health Survey), fatigue (Checklist Individual Strength), and peripheral neuropathy symptoms (EORTC QLQ-CIPN20) were assessed in all participants and associations with self-reported participation satisfaction were analyzed by multivariable logistic regression models.Results: 19% of CRC survivors reported dissatisfaction with participation. Participation restrictions were reported for interpersonal relationships, work/employment, and social/civic life. CRC survivors reporting better physical and emotional role functioning were significantly less likely to be dissatisfied with their participation, whereas survivors reporting higher levels of fatigue or more peripheral neuropathy symptoms were more likely to be dissatisfied with participation.Conclusions: Colorectal cancer (treatment) related health and functioning problems negatively impacts the ability of nearly 1 in 5 long-term CRC survivors to participate in everyday life situations and their satisfaction with participation. Follow-up care needs to be able to identify and address these problems.</p

IL-6-induced anaemia in rats:Possible pathogenetic implications for anaemia observed in chronic inflammations

Anaemia of chronic disease (ACD) is frequently found in rheumatoid arthritis (RA). In the pathogenesis of ACD both cytokines, such as tumour necrosis factor-alpha (TNF-α), IL-1 and IL-6 as well as a relative deficiency of erythropoietin (EPO), are thought to play a key role. In the present study the role of IL-6 in the pathogenesis of this anaemia was investigated. IL-6 was administered intraperitoneally to rats for 14 sequential days. It appeared that IL-6 was able to induce anaemia. No evidence for suppression of bone marrow erythropoiesis or enhanced sequestration of erythrocytes in the liver was found. However, decreased plasma and bone marrow iron contents were observed in anaemic rats. Blood loss in intestinal tissue was demonstrated using erythrocyte labelling with 99mtechnetium. Histologically this was associated with inflammatory cell infiltration, oedema and bleeding in the intestinal wall. In conclusion, IL-6 induced anaemia in rats. This anaemia was caused by intestinal blood loss.</p

Self-diffusion in dense granular shear flows

Diffusivity is a key quantity in describing velocity fluctuations in granular materials. These fluctuations are the basis of many thermodynamic and hydrodynamic models which aim to provide a statistical description of granular systems. We present experimental results on diffusivity in dense, granular shear in a 2D Couette geometry. We find that self-diffusivities are proportional to the local shear rate with diffusivities along the mean flow approximately twice as large as those in the perpendicular direction. The magnitude of the diffusivity is D \approx \dot\gamma a^2 where a is the particle radius. However, the gradient in shear rate, coupling to the mean flow, and drag at the moving boundary lead to particle displacements that can appear sub- or super-diffusive. In particular, diffusion appears superdiffusive along the mean flow direction due to Taylor dispersion effects and subdiffusive along the perpendicular direction due to the gradient in shear rate. The anisotropic force network leads to an additional anisotropy in the diffusivity that is a property of dense systems with no obvious analog in rapid flows. Specifically, the diffusivity is supressed along the direction of the strong force network. A simple random walk simulation reproduces the key features of the data, such as the apparent superdiffusive and subdiffusive behavior arising from the mean flow, confirming the underlying diffusive motion. The additional anisotropy is not observed in the simulation since the strong force network is not included. Examples of correlated motion, such as transient vortices, and Levy flights are also observed. Although correlated motion creates velocity fields qualitatively different from Brownian motion and can introduce non-diffusive effects, on average the system appears simply diffusive.Comment: 13 pages, 20 figures (accepted to Phys. Rev. E

Appropriate use criteria for echocardiography in the Netherlands

Introduction Appropriate use criteria (AUC) for echocardiography based on clinical scenarios were previously published by an American Task Force. We determined whether members of the Dutch Working Group on Echocardiography (WGE) would rate these scenarios in a similar way. Methods All 32 members of the WGE were invited to judge clinical scenarios independently using a blanked version of the previously published American version of AUC for echocardiography. During a face-to-face meeting, consensus about the final rating was reached by open discussion for each indication. For reasons of simplicity, the scores were reduced from a 9-point scale to a 3-point scale (indicating an appropriate, uncertain or inappropriate echo indication, respectively). Results Nine cardiologist members of the WGE reported their judgment on the echo cases (n = 153). Seventy-one indications were rated as appropriate, 35 were rated as uncertain, and 47 were rated as inappropriate. In 5% of the cases the rating was opposite to that in the original (appropriate compared with inappropriate and vice versa), whereas in 20% judgements differed by 1 level of appropriateness. After the consensus meeting, the appropriateness of 7 (5%) cases was judged differently compared with the original paper. Conclusions Echocardiography was rated appropriate when it is applied for an initial diagnosis, a change in clinical status or a change in patient management. However, in about 5% of the listed clinical scenarios, members of the Dutch WGE rated the AUC for echocardiography differently as compared with their American counterparts. Further research is warranted to analyse this decreased external validity

Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig