The physics of water and wax in the pores of a working Gas-to-Liquids catalyst

The so-called Fischer-Tropsch catalysis allows to convert natural gas into liquid products and is the underlying mechanism of commercially used "Gas-to-Liquids" plants. The actual reaction takes place in millimetre sized porous pellets in which active metallic particles are dispersed as catalysts. Due to the reaction the pores of the pellets will become filled with the reaction products ("wax" and water), but it is uncertain if the fluid in the pores can be understood as a single liquid phase, a liquid-gas mixture, or multiple continuous phases. The answer to this question is important for a thorough understanding of the transport processes inside the reactor and can be utilized to improve its eciency. In this project, a theoretical analysis of the behaviour inside the pores is performed. It is concluded that a liquid water phase might well exist next to the wax phase. However, the analysis is based on very limited experimental data of unknown quality. Therefore, we propose a number of possible experiments to validate the theoretical concepts

Acute symptoms during the course of head and neck radiotherapy or chemoradiation are strong predictors of late dysphagia

AbstractPurposeTo determine if acute symptoms during definitive radiotherapy (RT) or chemoradiation (CHRT) are prognostic factors for late dysphagia in head and neck cancer (HNC).Material and methodsThis prospective cohort study consisted of 260 HNC patients who received definitive RT or CHRT. The primary endpoint was grade 2–4 swallowing dysfunction at 6months after completing RT (SWALM6). During treatment, acute symptoms, including oral mucositis, xerostomia and dysphagia, were scored, and the scores were accumulated weekly and entered into an existing reference model for SWALM6 that consisted of dose–volume variables only.ResultsBoth acute xerostomia and dysphagia were strong prognostic factors for SWALM6. When acute scores were added as variables to the reference model, model performance increased as the course of treatment progressed: the AUC rose from 0.78 at the baseline to 0.85 in week 6. New models built for weeks 3–6 were significantly better able to identify patients with and without late dysphagia.ConclusionAcute xerostomia and dysphagia during the course of RT are strong prognostic factors for late dysphagia. Including accumulated acute symptom scores on a weekly basis in prediction models for late dysphagia significantly improves the identification of high-risk and low-risk patients at an early stage during treatment and might facilitate individualized treatment adaptation

Impact of sarcopenia on survival and late toxicity in head and neck cancer patients treated with radiotherapy

Background and purpose: Sarcopenia is emerging as an adverse prognostic factor for survival and complication risk in cancer patients. This study aims to determine the impact of sarcopenia on survival and late toxicity in a large cohort of head and neck squamous cell carcinoma (HNSCC) patients treated with definitive (chemo)radiotherapy ((C)RT). Materials and methods: HNSCC patients treated with definitive (C)RT from January 2007 to June 2016 were included. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscles at level C3. The impact of sarcopenia on overall survival (OS) and disease-free survival (DFS) was evaluated using the Kaplan–Meier method. Multivariable association models were developed to assess the impact of sarcopenia on late toxicity. Results: The study population was composed of 750 HNSCC patients. Cut-off values for sarcopenia were set at SMI < 42.4 cm2/m2 (men) and <30.6 cm2/m2 (women) corresponding lowest gender specific quartile. Sarcopenic patients had significantly poorer survival rates, especially those with lower performance status and locally advanced disease. In oropharyngeal cancer patients, survival was more determined by p16 status than by sarcopenia. In multivariable analysis, sarcopenia was associated with worse OS (HR 0.72, p = 0.012) and DFS (HR 0.67, p = 0.001). In multivariable association models, sarcopenia was associated with physician-rated xerostomia six months after treatment (OR 1.65, p = 0.027) and physician-rated dysphagia six and twelve months after treatment (OR 2.02, p = 0.012 and 2.51, p = 0.003, respectively). Conclusion: Sarcopenia in HNSCC patients receiving definitive (C)RT is an independent prognostic factor for worse survival outcomes and is associated with physician-rated toxicity

Relationship between videofluoroscopic and subjective (physician- and patient- rated) assessment of late swallowing dysfunction after (chemo) radiation:Results of a prospective observational study

BACKGROUND AND PURPOSE: Primary (chemo)radiation (CHRT) for HNC may lead to late dysphagia. The purpose of this study was to assess the pattern of swallowing disorders based on prospectively collected objective videofluoroscopic (VF) assessment and to assess the correlations between VF findings and subjective (physician- and patient-rated) swallowing measures. MATERIAL AND METHODS: 189 consecutive HNC patients receiving (CH)RT were included. Swallowing evaluation at baseline and 6 months after treatment (T6) encompassed: CTCAE v.4.0 scores (aspiration/dysphagia), PROMs: SWAL QOL/ EORTC QLQ-H&N35 (swallowing domain) questionnaires and VF evaluation: Penetration Aspiration Scale, semi-quantitative swallowing pathophysiology evaluation, temporal measures and oral/pharyngeal residue quantification. Aspiration specific PROMs (aPROMs) were selected. Correlations between late penetration/aspiration (PA_T6) and: clinical factors, CTCAE and aPROMs were assessed using uni- and multivariable analysis. RESULTS: Prevalence of PA increased from 20% at baseline to 43% after treatment (p<0.001).The most relevant baseline predictors for PA_T6 were: PA_T0, age, disease stage III-IV, bilateral RT and baseline aPROM 'Choking when drinking' (AUC: 0.84). In general aPROMs correlated better with VF-based PA than CTCAE scores. The most of physiological swallowing components significantly correlated and predictive for PA (i.e. Laryngeal Vestibular Closure, Laryngeal Elevation and Pharyngeal Contraction) were prone to radiation damage. CONCLUSION: The risk of RT-induced PA is substantial. Presented prediction models for late penetration/aspiration may support patient selection for baseline and follow-up VF examination. Furthermore, all aspiration related OARs involved in aforementioned swallowing components should be addressed in swallowing sparing strategies. The dose to these structures as well as baseline PROMs should be included in future NTCP models for aspiration

Talking quiescence: a rigorous theory that supports parallel composition, action hiding and determinisation

The notion of quiescence - the absence of outputs - is vital in both behavioural modelling and testing theory. Although the need for quiescence was already recognised in the 90s, it has only been treated as a second-class citizen thus far. This paper moves quiescence into the foreground and introduces the notion of quiescent transition systems (QTSs): an extension of regular input-output transition systems (IOTSs) in which quiescence is represented explicitly, via quiescent transitions. Four carefully crafted rules on the use of quiescent transitions ensure that our QTSs naturally capture quiescent behaviour. We present the building blocks for a comprehensive theory on QTSs supporting parallel composition, action hiding and determinisation. In particular, we prove that these operations preserve all the aforementioned rules. Additionally, we provide a way to transform existing IOTSs into QTSs, allowing even IOTSs as input that already contain some quiescent transitions. As an important application, we show how our QTS framework simplifies the fundamental model-based testing theory formalised around ioco.Comment: In Proceedings MBT 2012, arXiv:1202.582

Effect of dose reduction on image quality and diagnostic performance in coronary computed tomography angiography

To evaluate the effect of radiation dose reduction on image quality and diagnostic accuracy of coronary computed tomography (CT) angiography. Coronary CT angiography studies of 40 patients with (n = 20) and without (n = 20) significant (≥50 %) stenosis were included (26 male, 14 female, 57 ± 11 years). In addition to the original clinical reconstruction (100 % dose), simulated images were created that correspond to 50, 25 and 12.5 % of the original dose. Image quality and diagnostic performance in identifying significant stenosis were determined. Receiver–operator-characteristics analysis was used to assess diagnostic accuracy at different dose levels. The identification of patients with significant stenosis decreased consistently at doses of 50, 25 and 12.5 of the regular clinical acquisition (100 %). The effect was relatively weak at 50 % dose, and was strong at dose levels of 25 and 12.5 %. At lower doses a steady increase was observed for false negative findings. The number of coronary artery segments that were rated as diagnostic decreased gradually with dose, this was most prominent for smaller segments. The area-under-the-curve (AUC) was 0.90 (p = 0.4) at 50 % dose; accuracy decreased significantly with 25 % (AUC 0.70) and 12.5 % dose (AUC 0.60) (p < 0.0001), with underestimation of patients having significant stenosis. The clinical acquisition protocol for evaluation of coronary artery stenosis with CT angiography represents a good balance between image quality and patient dose. A potential for a modest (<50 %) reduction of tube current might exist. However, more substantial reduction of tube current will reduce diagnostic performance of coronary CT angiography substantially

Selection of head and neck cancer patients for adaptive radiotherapy to decrease xerostomia

AbstractBackground and purposeThe aim of this study was to develop and validate a method to select head and neck cancer patients for adaptive radiotherapy (ART) pre-treatment. Potential pre-treatment selection criteria presented in recent literature were included in the analysis.Materials and methodsDeviations from the planned parotid gland mean dose (PG ΔDmean) were estimated for 113 head and neck cancer patients by re-calculating plans on repeat CT scans. Uni- and multivariable linear regression analyses were performed to select pre-treatment parameters, and ROC curve analysis was used to determine cut off values, for selecting patients with a PG dose deviation larger than 3Gy. The patient selection method was validated in a second patient cohort of 43 patients.ResultsAfter multivariable analysis, the planned PG Dmean remained the only significant parameter for PG ΔDmean. A sensitivity of 91% and 80% could be obtained using a threshold of PG Dmean of 22.2Gy, for the development and validation cohorts, respectively. This would spare 38% (development cohort) and 24% (validation cohort) of patients from the labour-intensive ART procedure.ConclusionsThe presented method to select patients for ART pre-treatment reduces the labour of ART, contributing to a more effective allocation of the department resources

Parotid Gland Stem Cell Sparing Radiation Therapy for Patients With Head and Neck Cancer:A Double-Blind Randomized Controlled Trial

BACKGROUND: Radiotherapy for head and neck cancer (HNC) frequently leads to salivary gland damage and subsequent xerostomia. The radiation response of parotid glands of rats, mice, and patients critically depends on dose to its stem cells, mainly located in the gland's main ducts (stem cell rich (SCR) region). Therefore, this double-blind randomized controlled trial aimed to test the hypothesis that parotid gland stem cell sparing radiotherapy preserves parotid gland function better than currently-used whole parotid gland sparing radiotherapy. METHODS: HNC patients (n=102) treated with definitive radiotherapy were randomized between standard parotid sparing and stem cell sparing (SCS) techniques. The primary endpoint was >75% reduction in parotid gland saliva production compared to pretreatment production (FLOW12M). Secondary endpoints were several aspects of xerostomia 12 months after treatment. RESULTS: Fifty-four patients were assigned to the standard arm and 48 to the SCS arm. Only dose to the SCR regions (contralateral 16 and 11 Gy (p=0.004) and ipsilateral 26 and 16 Gy (p=0.001), standard and SCS arm respectively) and pretreatment patient-rated daytime xerostomia (35% and 13% (p=0.01), standard and SCS arm respectively) differed significantly between the arms. In the SCS arm, 1 patient (2.8%) experienced FLOW12M compared to 2 (4.9%) in the standard arm (p=1.00). However, a trend towards better relative parotid gland salivary function in favor of SCS radiotherapy was shown. Moreover, multivariable analysis showed that mean contralateral SCR region dose was the strongest dosimetric predictor for moderate-to-severe patient-rated daytime xerostomia and grade ≥2 physician-rated xerostomia, the latter including complaints of alteration in diet. CONCLUSIONS: No significant better parotid function was observed in SCS radiotherapy. However, additional multivariable analysis showed that dose to the SCR region was more predictive for development of parotid gland function related xerostomia endpoints, than dose to the entire parotid gland

Pre-treatment radiomic features predict individual lymph node failure for head and neck cancer patients

Background and purpose: To develop and validate a pre-treatment radiomics-based prediction model to identify pathological lymph nodes (pLNs) at risk of failures after definitive radiotherapy in head and neck squamous cell carcinoma patients. Materials and methods: Training and validation cohorts consisted of 165 patients with 558 pLNs and 112 patients with 467 pLNs, respectively. All patients were primarily treated with definitive radiotherapy, with or without systemic treatment. The endpoint was the cumulative incidence of nodal failure. For each pLN, 82 pre-treatment CT radiomic features and 7 clinical features were included in the Cox proportional-hazard analysis. Results: There were 68 and 23 nodal failures in the training and validation cohorts, respectively. Multivariable analysis revealed three clinical features (T-stage, gender and WHO Performance-status) and two radiomic features (Least-axis-length representing nodal size and gray level co-occurrence matrix based - Correlation representing nodal heterogeneity) as independent prognostic factors. The model showed good discrimination with a c-index of 0.80 (0.69–0.91) in the validation cohort, significantly better than models based on clinical features (p < 0.001) or radiomics (p = 0.003) alone. High- and low-risk groups were defined by using thresholds of estimated nodal failure risks at 2-year of 60% and 10%, resulting in positive and negative predictive values of 94.4% and 98.7%, respectively. Conclusion: A pre-treatment prediction model was developed and validated, integrating the quantitative radiomic features of individual lymph nodes with generally used clinical features. Using this prediction model, lymph nodes with a high failure risk can be identified prior to treatment, which might be used to select patients for intensified treatment strategies targeted on individual lymph nodes