Ocean-going ships are mostly driven by high‑sulfur heavy fuel oil, which poses public health and environmental concerns. Emission control areas (ECA) have been developed for the regulatory control of ...the sulfur content in fuel. We tracked 28 sample vessels that entered and exited Shanghai Port, to understand how air pollutants, including oxysulfides (SOx), nitric oxide (NOx), and particulate matter smaller than 10 μm (PM10), would change under the ECA regulations. Emission reductions vary with the types and sizes of the ships. In our sample pool, oil/chemical tankers and container ships have the highest decline rates of SOx emissions at 26.8%–56.4% and 17.4%–56.6%, respectively. Cruise ships, container ships, and liquefied gas carriers occupy the highest share ratios of pollutant emissions in the sample pool because of the higher average gross tonnage and correspondingly higher-rated power of the ships' main engines. As expected, SOx and PM10 emissions under hoteling conditions (operations while stationary at dock) can be considerably reduced by switching to low-sulfur fuel. Using fuel with the much lower sulfur content of 0.1% m/m in the ECA, the SOx and PM10 emissions of our sample pool could be reduced considerably by up to 94.4% and 78.3%, respectively, compared to the 0.5% m/m sulfur content used during ship hoteling.
•Emission control areas (ECA) have been developed for regulatory control of sulfur content in fuel.•We tracked 28 vessels to understand how air pollutants would change under the ECA regulations.•Emission reductions vary with the types and sizes of the ships.•Oil/chemical tankers and container ships have the highest decline rates of SOx emissions.•Oxysulfides and particulate matter emissions under hoteling conditions can be considerably reduced with lower sulfur fuel.•ECA regulations are effective and more coastal nations should consider implement a similar scheme.
This study aims to utilize a hybrid approach of phantom correction and deep learning for synthesized CT (sCT) images generation based on cone-beam CT (CBCT) images for nasopharyngeal carcinoma (NPC). ...52 CBCT/CT paired images of NPC patients were used for model training (41), validation (11). Hounsfield Units (HU) of the CBCT images was calibrated by a commercially available CIRS phantom. Then the original CBCT and the corrected CBCT (CBCT_cor) were trained separately with the same cycle generative adversarial network (CycleGAN) to generate SCT1 and SCT2. The mean error and mean absolute error (MAE) were used to quantify the image quality. For validations, the contours and treatment plans in CT images were transferred to original CBCT, CBCT_cor, SCT1 and SCT2 for dosimetric comparison. Dose distribution, dosimetric parameters and 3D gamma passing rate were analyzed. Compared with rigidly registered CT (RCT), the MAE of CBCT, CBCT_cor, SCT1 and SCT2 were 346.11 ± 13.58 HU, 145.95 ± 17.64 HU, 105.62 ± 16.08 HU and 83.51 ± 7.71 HU, respectively. Moreover, the average dosimetric parameter differences for the CBCT_cor, SCT1 and SCT2 were 2.7% ± 1.4%, 1.2% ± 1.0% and 0.6% ± 0.6%, respectively. Using the dose distribution of RCT images as reference, the 3D gamma passing rate of the hybrid method was significantly better than the other methods. The effectiveness of CBCT-based sCT generated using CycleGAN with HU correction for adaptive radiotherapy of nasopharyngeal carcinoma was confirmed. The image quality and dose accuracy of SCT2 were outperform the simple CycleGAN method. This finding has great significance for the clinical application of adaptive radiotherapy for NPC.
The aim of this study is to demonstrate the feasibility of a commercially available Auto-Planning module for the radiation therapy treatment planning for locally advanced nasopharyngeal carcinoma ...(NPC). 22 patients with locally advanced NPC were included in this study. For each patient, volumetric modulated arc therapy (VMAT) plans were generated both manually by an experienced physicist and automatically by the Auto-Planning module. The dose distribution, dosimetric parameters, monitor units and planning time were compared between automatic plans (APs) and manual plans (MPs). Meanwhile, the overall stage of disease was factored into the evaluation. The target dose coverage of APs was comparable to that of MPs. For the organs at risk (OARs) except spinal cord, the dose parameters of APs were superior to that of MPs. The D
and V
of brainstem were statistically lower by 1.0 Gy and 1.32% respectively, while the D
of optic nerves and chiasm were also lower in the APs (p < 0.05). The APs provided a similar or superior quality to MPs in most cases, except for several patients with stage IV disease. The dose differences for most OARs were similar between the two types of plans regardless of stage while the APs provided better brainstem sparing for patients with stage III and improved the sparing of the parotid glands for stage IV patients. The total monitor units and planning time were significantly reduced in the APs. Auto-Planning is feasible for the VMAT treatment planning for locally advanced NPC.
Abstract This study employed a commercial software velocity to perform deformable registration and dose calculation on deformed CT images, aiming to assess the accuracy of dose delivery during the ...radiotherapy for lung cancers. A total of 20 patients with lung cancer were enrolled in this study. Adaptive CT (ACT) was generated by deformed the planning CT (pCT) to the CBCT of initial radiotherapy fraction, followed by contour propagation and dose recalculation. There was not significant difference between volumes of GTV and CTV calculated from the ACT and pCT. However, significant differences in dice similarity coefficient (DSC) and coverage ratio (CR) between GTV and CTV were observed, with lower values for GTV volumes below 15 cc. The mean differences in dose corresponding to 95% of the GTV, GTV-P, CTV, and CTV-P between ACT and pCT were − 0.32%, 4.52%, 2.17%, and 4.71%, respectively. For the dose corresponding to 99%, the discrepancies were − 0.18%, 8.35%, 1.92%, and 24.96%, respectively. These differences in dose primarily appeared at the edges of the target areas. Notably, a significant enhancement of dose corresponding to 1 cc for spinal cord was observed in ACT, compared with pCT. There was no statistical difference in the mean dose of lungs and heart. In general, for lung cancer patients, anatomical motion may result in both CTV and GTV moving outside the original irradiation region. The dose difference within the original target area was small, but the difference in the planning target area was considerable.
HDAC11 is an epigenetic repressor of gene transcription, acting through its deacetylase activity to remove functional acetyl groups from the lysine residues of histones at genomic loci. It has been ...implicated in the regulation of different immune responses, metabolic activities, as well as cell cycle progression. Recent studies have also shed lights on the impact of HDAC11 on myogenic differentiation and muscle development, indicating that HDAC11 is important for histone deacetylation at the promoters to inhibit transcription of cell cycle related genes, thereby permitting myogenic activation at the onset of myoblast differentiation. Interestingly, the upstream networks of HDAC11 target genes are mainly associated with cell cycle regulators and the acetylation of histones at the HDAC11 target promoters appears to be residue specific. As such, selective inhibition, or activation of HDAC11 presents a potential therapeutic approach for targeting distinct epigenetic pathways in clinical applications.
Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant ...disability, morbidity, and mortality.
Here we describe the rationale and design of the Phase 3 APOLLO study, a randomized, double-blind, placebo-controlled, global study to evaluate the efficacy and safety of patisiran in patients with hATTR amyloidosis with polyneuropathy. Eligible patients are 18-85 years old with hATTR amyloidosis, investigator-estimated survival of ≥2 years, Neuropathy Impairment Score (NIS) of 5-130, and polyneuropathy disability score ≤IIIb. Patients are randomized 2:1 to receive either intravenous patisiran 0.3 mg/kg or placebo once every 3 weeks. The primary objective is to determine the efficacy of patisiran at 18 months based on the difference in the change in modified NIS+7 (a composite measure of motor strength, sensation, reflexes, nerve conduction, and autonomic function) between the patisiran and placebo groups. Secondary objectives are to evaluate the effect of patisiran on Norfolk-Diabetic Neuropathy quality of life questionnaire score, nutritional status (as evaluated by modified body mass index), motor function (as measured by NIS-weakness and timed 10-m walk test), and autonomic symptoms (as measured by the Composite Autonomic Symptom Score-31 questionnaire). Exploratory objectives include assessment of cardiac function and pathologic evaluation to assess nerve fiber innervation and amyloid burden. Safety of patisiran will be assessed throughout the study.
APOLLO represents the largest randomized, Phase 3 study to date in patients with hATTR amyloidosis, with endpoints that capture the multisystemic nature of this disease.
This trial is registered at clinicaltrials.gov ( NCT01960348 ); October 9, 2013.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose:
To develop and evaluate an automatic intensity-modulated radiation therapy (IMRT) program for cervical cancer, including a Convolution Neural Network (CNN)-based prediction model and an ...automated optimization strategy.
Methods:
A CNN deep learning model was trained to predict a patient-specify set of IMRT objectives based on overlap volume histograms (OVH) and high-quality plan of previous patients. A total of 140 cervical cancer patients were enrolled in this study, including 100 patients in the training set, 20 patients in the validation set and 20 patients in the testing set. The input of this model was OVH data and the output were values of IMRT plan objectives. For patients in the testing set, the set of planning objectives were predicted by the CNN model and used to automatically generate IMRT plans. Meanwhile, manual plans of these patients were generated by 1 beginner planner and 1 senior planner respectively. Finally, dose distribution, dosimetric parameters and planning time were analyzed. In addition, the 3 types of plans were blinded compared and ranked by an experienced oncologist.
Results:
There were almost no statistically differences among these 3 types of plans in target coverage and dose conformity. Dose homogeneity were slightly decreased while the average dose and parameters for most organs-at-risk (OARs) were decreased in automatic plans. Especially in comparison with manual plans by the beginner planner, V40 of bladder and rectum decreased 6.3% and 12.3%, while mean dose of rectum and marrow were 1.1 Gy and 1.8 Gy lower with automatic plans (either P < 0.017). In the blinded comparison, automatic plans were chosen as best plan in 14 cases.
Conclusions:
For cervical cancer, automatic IMRT plans optimized from the CNN generated objectives have superior dose sparing without compromising of target dose. It significantly reduced the planning time.
This paper explores the decision-making and coordination mechanism of pricing and collection rate in a closed-loop supply chain with capacity constraint in recycling channels, which consists of one ...manufacturer and one retailer. On the basis of game theory, the equilibriums of decisions and profits in the centralized and decentralized scenarios are obtained and compared. Through the performance analysis of a different scenario, a higher saving production cost and lower competition intensity trigger the members to engage in remanufacturing. Furthermore, we try to propose a two-part tariff contract through bargaining to coordinate supply chain and achieve a Pareto improvement. The results show that when the capacity constraints in recycling channels exceed a threshold, the decisions and profit will change. Additionally, for closed-loop supply chain, the selling price is more susceptible to the influence of capacity constraint in recycling channel than the members’ profit.
Advanced robotic applications have revived interest in identification of a high-precision dynamic model. In this article, we propose an extended dynamic parameter set (EDS). The EDS breaks through ...the limitation that the base dynamic parameter set needs a priori knowledge of the gravity direction for modeling. Moreover, we present a novel parameters identification technique (RSIH), which is a complete solution and can significantly mitigate negative effects of the measurement noise and outliers. Besides, an incremental learning technique combined with a compensation limit criterion is employed to compensate for unmodeled dynamics. Simulations and experiments demonstrate the EDS-based model can adapt to any installation angle of a base plate, and confirm the RSIH technique outperforms the widely used identification techniques in industry and is equal to or even better than the state-of-the-art physical feasibility technique in terms of identification precision and robustness. In addition, the modeling errors, especially the uncertainty of the friction model, can be greatly compensated.
Summary Background Adrenocortical carcinoma is a rare, aggressive cancer for which few treatment options are available. Linsitinib (OSI-906) is a potent, oral small molecule inhibitor of both IGF-1R ...and the insulin receptor, which has shown acceptable tolerability and preliminary evidence of anti-tumour activity. We assessed linsitinib against placebo to investigate efficacy in patients with advanced adrenocortical carcinoma. Methods In this international, double-blind, placebo-controlled phase 3 study, adult patients with histologically confirmed locally advanced or metastatic adrenocortical carcinoma were recruited at clinical sites in nine countries. Patients were randomly assigned (2:1) twice-daily 150 mg oral linsitinib or placebo via a web-based, centralised randomisation system and stratified according to previous systemic cytotoxic chemotherapy for adrenocortical carcinoma, Eastern Cooperative Oncology Group performance status, and use of one or more oral antihyperglycaemic therapy at randomisation. Allocation was concealed by blinded block size and permuted block randomisation. The primary endpoint was overall survival, calculated from date of randomisation until death from any cause. The primary analysis was done in the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT00924989. Findings Between Dec 2, 2009, and July 11, 2011, 139 patients were enrolled, of whom 90 were assigned to linsitinib and 49 to placebo. The trial was unblinded on March 19, 2012, based on data monitoring committee recommendation due to the failure of linsitinib to increase either progression-free survival or overall survival. At database lock and based on 92 deaths, no difference in overall survival was noted between linsitinib and placebo (median 323 days 95% CI 256–507 vs 356 days 249–556; hazard ratio 0·94 95% CI 0·61–1·44; p=0·77). The most common treatment-related adverse events of grade 3 or worse in the linsitinib group were fatigue (three 3% patients vs no patients in the placebo group), nausea (two 2% vs none), and hyperglycaemia (two 2% vs none). No adverse events in the linsitinib group were deemed to be treatment related; one death (due to sepsis and megacolon) in the placebo group was deemed to be treatment related. Interpretation Linsitinib did not increase overall survival and so cannot be recommended as treatment for this general patient population. Further studies of IGF-1R and insulin receptor inhibitors, together with genetic profiling of responders, might pave the way toward individualised and improved therapeutic options in adrenocortical carcinoma. Funding Astellas.
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