33 research outputs found
Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy
No full textPurposeCurrent normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation.Methods and MaterialsFDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares–logistic regression [FPLS-LR] and functional principal component–logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate–response associations, assessed using bootstrapping.ResultsThe area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models.ConclusionsFPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling
Geometric and dosimetric evaluation of the differences between rigid and deformable registration to assess interfraction motion during pelvic radiotherapy
No full textBackground and purpose: Appropriate internal margins are essential to avoid a geographical miss in intensity-modulated radiation therapy (IMRT) for endometrial cancer (EC). This study evaluated interfraction target motion using rigid and non-rigid approximation strategies and calculated internal margins based on random and systematic errors using traditional rigid margin recipes. Dosimetric impact of target motion was also investigated. Materials and methods: Cone beam CTs (CBCTs) were acquired days 1–4 and then weekly in 17 patients receiving adjuvant IMRT for EC; a total of 169 CBCTs were analysed. Interfraction motion for the clinical target volume vaginal vault and upper vagina (CTVv) was measured using bony landmarks and deformation vector field displacement (DVFD) within a 1 mm internal wall of CTVv. Patient and population systematic and random errors were estimated and margins calculated. Delivered dose to the CTVv and organs at risk was estimated. Results: There was a significant difference in target motion assessment using the different registration strategies (p < 0.05). DVFD up to 30 mm occurred in the anterior/posterior direction, which was not accounted for in PTV margins using rigid margin recipes. Underdosing of CTVv D95% occurred in three patients who had substantial reductions in rectal volume (RV) during treatment. RV relative to the planning CT was moderately correlated with anterior/posterior displacement (r = 0.6) and mean relative RV during treatment was strongly correlated with mean relative RV at CBCT acquired days 1–3 (r = 0.8). Conclusion: Complex and extensive geometric changes occur to the CTVv, which are not accounted for in margin recipes using rigid approximation. Contemporary margin recipes and adaptive treatment planning based on non-rigid approximation are recommended
Reconfigurable modular battery pack for electric aircraft
No full textAviation is a growing industry responsible for over 2% of the energy-related CO2 emissions in 2021. To achieve the 'Net Zero Emission by 2050 scenario', the aviation industry is turning towards modern propulsion technologies that reduce carbon and NOx emissions. Research is taking place on many prospective aircraft designs, such as hybrid/turbo-electric powertrains, fuel cell/liquid hydrogen-powered aircraft and fully electric aircraft. Although fully electric aircraft offer the cleanest possible air travel, these aircraft are considered the solution for short-haul flights due to the range extension issue caused by the deficient specific energy of batteries compared to currently used aviation fuel. The electric aircraft concept designers rely on the potential development in battery technology while proposing their designs, and sporadic state-of-the-art battery designs are present concerning electric aviation. The concept of reconfigurable battery packs involves using power switches to modify the arrangement of connected battery cells based on specific requirements. This innovative technique can potentially significantly reduce the weight of battery packs. The primary objective of this thesis was to conduct a comprehensive analysis and comparison between fixed configuration and reconfigurable battery packs in the context of electric aviation. It was imperative first to design these battery packs to facilitate this comparison. Given the limited availability of open data on electric aircraft designs, the power profile was estimated using available reference aircraft specifications and reasonable assumptions. The literature review on power systems in aircraft revealed a significant correlation between system-level voltage and the weight of power cables. This discovery led to estimating an optimal system-level voltage, a critical constraint in battery sizing. For the fixed configuration battery pack, sizing was conducted using both a high-specific energy cell and a high-specific power cell. The design of a reconfigurable battery pack involved strategically leveraging both cell types. This innovative approach created a reconfigurable battery pack capable of dynamically connecting and disconnecting an internal high-specific energy battery pack called the 'primary battery pack' and a high-specific power battery pack known as the 'secondary battery pack' through power switches, allowing them to complement each other during high-power demand phases of flight, such as take-off and climbing.Software simulations were conducted for the validation of this technique. These simulations revealed that the reconfigurable battery pack experienced higher C-rates than the fixed configuration battery pack. Given that higher C-rates can impact battery health by inducing capacity loss over multiple cycles, a preliminary ageing analysis was performed to quantitatively assess the adverse effects of higher C-rates on the reconfigurable battery pack.The results quantified that around 400 kg of potential weight savings is possible by employing reconfigurable battery packs over fixed configuration battery packs at only 0.4% more capacity loss over 500 charging-discharging cycles. The weight savings can be translated into three different scenarios. Firstly, payload weight capacity can be enhanced. Secondly, flying with lesser weight will offset the power profile, saving energy. Lastly, an additional number of cells equivalent to the mass saved can realise the range extension of the electric aircraft.Electrical Engineering | Sustainable Energy Technolog
Active Inference Control for Vehicle Platooning
No full textDue to the increase in traffic, road congestion has gone up. Vehicle platooning is a possible way to increase the capacity of a given road, by decreasing the distance between the vehicles in the platoon. At the moment, the control of vehicle platoons is commonly done using PID controllers. The advantage of this is that it requires little computational resources. With improvements in computing technology in recent years, the possibility of using a more computationally costly method has opened up. But, parallel with that, dealing with inherently unmodeled dynamics and large parameter variations or faults, is a challenging task whilecontrolling any system. Classical control techniques do not provide satisfactory responses in most of the settings, and often external supervision systems have to be designed to handle the faults. Recent research has shown that active inference, a unifying neuroscientific theory of the brain, bares the potential of intrinsically coping with strong uncertainties in the system, mimicking the adaptability capabilities of humans. However, the current state-of-the-art regarding active inference in vehicle platooning is non-existent. This thesis presents a novel active inference controller for adaptive cruise control systems and as a general adaptive fault tolerant solution for control of vehicle platoon. First, we demonstrate the applicability of active inference in classical control scheme in order to control a platoon of vehicles. Second, we verify that the proposed active inference framework is computationally efficient and with high performance against a benchmark model. Third, we access the adaptive properties of the designed framework in presence of large parameter variations and actuator faults. This work reveals that not only active inference is applicable in vehicle platooning, but it also outperforms the benchmark model in some characteristics, and it allows to deal efficiently with parameter variations and actuator faults. This thesis represents a first step towards the implementation of the current state-of-the-art of active inference for vehicle platooning, and it lays the foundations for further research in this direction.Mechanical Engineering | Systems and Contro
Safety and Treatment Outcomes of Nivolumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Retrospective Multicenter Cohort Study.
No full textNivolumab is an anti-PD-1 monoclonal antibody currently used as immunotherapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with evidence of disease progression after platinum-based chemotherapy. This study evaluates real-world safety and treatment outcomes of non-trial nivolumab use. A retrospective multicenter cohort study of patients with recurrent/metastatic HNSCC treated with nivolumab between January 2017 and March 2020 was performed. Overall, 123 patients were included. The median age was 64 years, the majority of patients were male (80.5%) and had a smoking history (69.9%). Primary outcomes included overall response rate (ORR) of 19.3%, median progression-free survival (PFS) of 3.9 months, 1-year PFS rate of 16.8%, a median overall survival (OS) of 6.5 months and 1-year OS rate of 28.6%. These results are comparable to the CHECKMATE-141 study. Of 27 patients who had PD-L1 status tested, positive PD-L1 status did not significantly affect PFS ( = 0.86) or OS ( = 0.84). Nivolumab was well tolerated with only 15.1% experiencing immune-related toxicities (IRT) and only 6.7% of patients stopping due to toxicity. The occurrence of IRT appeared to significantly affect PFS ( = 0.01) but not OS ( = 0.07). Nivolumab in recurrent/metastatic HNSCC is well tolerated and may be more efficacious in patients who develop IRT
Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial
No full textBackground: most newly diagnosed oropharyngeal and hypopharyngeal cancers are treated with chemoradiotherapy with curative intent but at the consequence of adverse effects on quality of life. We aimed to investigate if dysphagia-optimised intensity-modulated radiotherapy (DO-IMRT) reduced radiation dose to the dysphagia and aspiration related structures and improved swallowing function compared with standard IMRT.Methods: DARS was a parallel-group, phase 3, multicentre, randomised, controlled trial done in 22 radiotherapy centres in Ireland and the UK. Participants were aged 18 years and older, had T1–4, N0–3, M0 oropharyngeal or hypopharyngeal cancer, a WHO performance status of 0 or 1, and no pre-existing swallowing dysfunction. Participants were centrally randomly assigned (1:1) using a minimisation algorithm (balancing factors: centre, chemotherapy use, tumour type, American Joint Committee on Cancer tumour stage) to receive DO-IMRT or standard IMRT. Participants and speech language therapists were masked to treatment allocation. Radiotherapy was given in 30 fractions over 6 weeks. Dose was 65 Gy to primary and nodal tumour and 54 Gy to remaining pharyngeal subsite and nodal areas at risk of microscopic disease. For DO-IMRT, the volume of the superior and middle pharyngeal constrictor muscle or inferior pharyngeal constrictor muscle lying outside the high-dose target volume had a mandatory 50 Gy mean dose constraint. The primary endpoint was MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after radiotherapy, analysed in the modified intention-to-treat population that included only patients who completed a 12-month assessment; safety was assessed in all randomly assigned patients who received at least one fraction of radiotherapy. The study is registered with the ISRCTN registry, ISRCTN25458988, and is complete.Findings: from June 24, 2016, to April 27, 2018, 118 patients were registered, 112 of whom were randomly assigned (56 to each treatment group). 22 (20%) participants were female and 90 (80%) were male; median age was 57 years (IQR 52–62). Median follow-up was 39·5 months (IQR 37·8–50·0). Patients in the DO-IMRT group had significantly higher MDADI composite scores at 12 months than patients in the standard IMRT group (mean score 77·7 [SD 16·1] vs 70·6 [17·3]; mean difference 7·2 [95% CI 0·4–13·9]; p=0·037). 25 serious adverse events (16 serious adverse events assessed as unrelated to study treatment [nine in the DO-IMRT group and seven in the standard IMRT group] and nine serious adverse reactions [two vs seven]) were reported in 23 patients. The most common grade 3–4 late adverse events were hearing impairment (nine [16%] of 55 in the DO-IMRT group vs seven [13%] of 55 in the standard IMRT group), dry mouth (three [5%] vs eight [15%]), and dysphagia (three [5%] vs eight [15%]). There were no treatment-related deaths.Interpretation: our findings suggest that DO-IMRT improves patient-reported swallowing function compared with standard IMRT. DO-IMRT should be considered a new standard of care for patients receiving radiotherapy for pharyngeal cancers.Funding: Cancer Research UK
Policy framework for autonomic data management
No full textThe popularity of e-Business has lead to an exponential and unstructured growth in the applications space coupled with an increase in the database size. This has led to an increase in the complexity of the database management task. Moreover, organizations are increasingly concerned about the privacy of data. Thus, managing such large ever growing and privacy-preserving database is complex and time-consuming task. In this paper we describe a policy-based framework for autonomic database management using Business Objects. Our system automatically manages data based on events. 1
Novel mutations in the toll like receptor genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection
No full textToll like receptors play a central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in TLR1, TLR2 and TLR4 genes may change the PAMP reorganization ability which causes altered responsiveness to the bacterial pathogens. A case control study, performed to assess the association between TLR gene mutations and susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP), revealed novel mutations (TLR1 - Ser150Gly and Val220Met; TLR2 - Phe670Leu) that hindered either PAMP recognition or further downstream TLR pathway activation. A cytokine expression experiments (IL-4, IL-8, IL-10, IL-12 and IFN-γ) in the challenged mutant and wild type moDCs (mocyte derived dendritic cells) confirmed the negative impact of these mutations and altered TLR downstream activation. Further In silico analysis of the TLR1 and TLR4 ectodomains (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR motifs. The most critical positions that may alter the pathogen recognition ability of TLR were: the 9th amino acid position in LRR motif (TLR1, LRR10) and 4th residue downstream to LRR domain (exta LRR region of TLR4). The study describes novel mutations in the TLRs and presents their association with the MAP infection
Effect of surface roughness in model and fresh fruit systems on microbial inactivation efficacy of cold atmospheric pressure plasma
No full textCold Atmospheric Pressure Plasma (CAPP) is an ionized gas consisting of charged and neutral particles, and radiation of varying wavelengths. Due to its relatively low temperature, CAPP is considered as a potential non-thermal decontamination technique. The goal of this research was to assess the suitability of CAPP for fresh produce decontamination as affected by surface roughness. The specific objectives were: i) to isolate and investigate the effect of surface roughness on microbial inactivation efficacy of CAPP using a model system, ii) to understand the extent to which surface roughness affects the microbial inactivation efficacy of CAPP in fresh produce, and iii) to detect and relatively quantify active plasma species in CAPP. CAPP from filtered dry air was generated using a plasma jet. Optical Emission Spectroscopy (OES) was used to quantify the relative concentrations of plasma species. Closed coat sandpapers with roughness (quantified via parameter of root mean square deviation Pq, measured using Confocal Laser Scanning Microscopy (CLSM)) ranging from, 6 µm to 16 µm were selected as model system. Sandpapers were inoculated with Enterobacter aerogenes (reportedly non-pathogenic, surrogate to Salmonella spp), left to dry for two hours, and treated with plasma for eight minutes twelve seconds. Based on their measured Pq values using CLSM, apples, oranges, and cantaloupes surfaces were selected and similar microbial inoculation, processing and analysis were performed. Model system results showed a 0.52 log higher inactivation of E. aerogenes (2.08 log inactivation) on the smoothest sandpaper and the difference was statistically significant from roughest sandpaper. Fruit surfaces results showed 1.25 log higher inactivation on apples (1.86 log inactivation) which were the smoothest and the difference was statistically significant from the roughest cantaloupes. As the surface roughness increased, the microbial inactivation efficacy of CAPP decreased. However, the results from fruit surfaces showed high variability, and were not predictable from the sandpaper data. Emission spectrum from OES indicated the presence of reactive oxygen and nitrogen species with potential to cause microbial inactivation. In conclusion, microbial inactivation efficacy of CAPP is affected by factors beyond surface roughness and further research is needed to determine its suitability for fresh produce decontamination.M.S.Includes bibliographical referencesby Siddharth Bhid
Effect of modern and traditional methods of preparation on the composition and flavor profiles of ghee
No full textGhee is a clarified milk-fat product originally from India. Ghee is prepared traditionally by culturing whole milk with lactic acid bacteria, prior to further processing steps. Industrially ghee is made by directly heating cream separated from whole milk. This research focuses on comparing chemical profiles of ghee made from different sources of milk and by different methods of preparation. Raw (non-pasteurized, non-homogenized) organic-grass fed cow milk and regular diet fed cow milk was obtained from Birchwood Farms, PA and Readington Farms, NJ respectively. Bacterial culture typical to ‘Dahi’ or Indian-style yogurt was obtained from Danisco. Ghee samples were made using these materials by three different methods (Direct cream method, Traditional method and Cultured cream method). Fatty acid profiles were elucidated using the FAMEs method using GC-MS. Non-saponifiable matter was analyzed using GC-Ms as well. Headspace volatiles were analyzed to elucidate differences in flavor profiles. Sensory evaluation was carried out on ghee made from grass-fed cow milk to identify whether the methods of preparation had an impact on the aroma profile. The results from all the analyses were compared for the different samples. Non-detectable differences were found in the fatty acid profiles and the non-saponifiable fractions of the different ghee samples. Cholesterol content in each sample was calculated. Method of preparation did not affect the chemical profiles of ghee significantly. Concentration of fatty acids was not affected by the source of milk or the method of preparation. This was analyzed by doing a two-factor ANOVA (Analysis of Variance). However, significant differences were found in their aroma profiles (based on sensory evaluation), instrumental color measurements and headspace volatile profiles. Thus the source of milk or method of preparation did not affect the fatty acid profiles of ghee however, method of preparation influenced the sensory properties and the flavor profiles.M.S.Includes bibliographical referencesby Neha M Bhid
