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Infrared transmission was employed to study the formation of a lubricating film deposited on two different substrates at 700 C. The deposit was formed from tricresylphosphate vapors and collected onto a NaCl substrate and on an iron coated NaCl substrate. Analysis of the infrared data suggests that a metal phosphate is formed initially, followed by the formation of organophosphorus polymeric compounds.
This project was a comprehensive research program for developing techniques for improving the performance of Internet protocols over Asynchronous Transfer Mode (ATM) based satellite networks. Among the service categories provided by ATM networks, the most commonly used category for data traffic is the unspecified bit rate (UBR) service. UBR allows sources to send data into the network without any feedback control. The project resulted in the numerous ATM Forum contributions and papers.
Asynchronous Transfer Mode (ATM) Quality of Service (QoS) experiments using the Transmission Control Protocol/Internet Protocol (TCP/IP) were performed for various link delays. The link delay was set to emulate a Wide Area Network (WAN) and a Satellite Link. The purpose of these experiments was to evaluate the ATM QoS requirements for applications that utilize advance TCP/IP protocols implemented with large windows and Selective ACKnowledgements (SACK). The effects of cell error, cell loss, and random bit errors on throughput were reported. The detailed test plan and test results are presented herein.
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Safety and reliability have long been recognized as key issues for the development, commercialization, and implementation of new technologies and infrastructure, and hydrogen systems are no exception to this rule. Reliability engineering, quantitative risk assessment (QRA), and knowledge exchange each play a key role in proactive addressing safety - before problems happen - and help us learn from problems if they happen. Many international research activities are focusing on both reliability and risk assessment for hydrogen systems. However, the element of knowledge exchange is sometimes less visible. To support international collaboration and knowledge exchange, the International Energy Agency (IEA) convened a new Technology Collaboration Program, "Task 43: Safety and Regulatory Aspects of Emerging Large Scale Hydrogen Energy Applications" started in June 2022. Within Task 43, Subtask E focuses on Hydrogen Systems Safety. This paper discusses the structure of the Hydrogen Systems Safety subtask and the aligned activities and introduces opportunities for future work.
Purpose: The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor-control-probability(TCP) with an acceptable normal-tissue-complication probability(NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. We design treatment plans that optimize TCP directly and contrast them with the clinical dose-based plans. PET image is incorporated to evaluate gain in TCP for dose escalation. Methods: We build a nonlinear mixed integer programming optimization model that maximizes TCP directly while satisfying the dose requirements on the targeted organ and healthy tissues. The solution strategy first fits the TCP function with a piecewise-linear approximation, then solves the problem that maximizes the piecewise linear approximation of TCP, and finally performs a local neighborhood search to improve the TCP value. To gauge the feasibility, characteristics, and potential benefit of PET-image guided dose escalation, initial validation consists of fifteen cervical cancer HDR patient cases. These patients have all received prior 45Gy of external radiation dose. For both escalated strategies, we consider 35Gy PTV-dose, and two variations (37Gy-boost to BTV vs 40Gy-boost) to PET-image-pockets. Results: TCP for standard clinical plans range from 59.4% - 63.6%. TCP for dose-based PET-guided escalated-dose-plan ranges from 63.8%–98.6% for all patients; whereas TCP-optimized plans achieves over 91% for all patients. There is marginal difference in TCP among those with 37Gy-boosted vs 40Gy-boosted. There is no increase in rectum and bladder dose among all plans. Conclusion: Optimizing TCP directly results in highly conformed treatment plans. The TCP-optimized plan is individualized based on the biological PET-image of the patients. The TCP-optimization framework is generalizable and has been applied successfully to other external-beam delivery modalities. A clinical trial is on-going to gauge the clinical significance. Partially supported by the National Science Foundation.
Purpose: SBRT with hypofractionated dose schemata has emerged a compelling treatment modality for medically inoperable early stage lung cancer patients. It requires more accurate dose calculation and treatment delivery technique. This report presents the relationship between tumor control probability(TCP) and size-adjusted biological effective dose(sBED) of tumor volume for MC lung SBRT patients. Methods: Fifteen patients who were treated with MC-based lung SBRT to 50Gy in 5 fractions to PTVV100%=95% were studied. ITVs were delineated on MIP images of 4DCT-scans. PTVs diameter(ITV+5mm margins) ranged from 2.7–4.9cm (mean 3.7cm). Plans were generated using non-coplanar conformal arcs/beams using iPlan XVMC algorithm (BrainLABiPlan ver.4.1.2) for Novalis-TX with HD-MLCs and 6MVSRS(1000MU/min) mode, following RTOG-0813 dosimetric guidelines. To understand the known uncertainties of conventional heterogeneities-corrected/uncorrected pencil beam (PBhete/ PB-homo) algorithms, dose distributions were re-calculated with PBhete/ PB-homo using same beam configurations, MLCs and monitor units. Biologically effective dose(BED10) was computed using LQ-model with α/β=10Gy for meanPTV and meanITV. BED10-c*L, gave size-adjusted BED(sBED), where c=10Gy/cm and L=PTV diameter in centimeter. The TCP model was adopted from Ohri et al.(IJROBP, 2012): TCP = exp[sBEDTCD50]/ k /(1.0 + exp[sBED-TCD50]/k), where k=31Gy corresponding to TCD50=0Gy; and more realistic MC-based TCP was computed for PTV(V99%). Results: Mean PTV PB-hete TCP value was 6% higher, but, mean PTV PB-homo TCP value was 4% lower compared to mean PTV MC TCP. Mean ITV PB-hete/PB-homo TCP values were comparable (within ±3.0%) to mean ITV MC TCP. The mean PTV(V99%)had BED10=90.9±3.7%(median=92.2%),sBED=54.1±8.2%(median=53.5%) corresponding to mean MC TCP value of 84.8±3.3%(median=84.9%) at 2- year local control. Conclusion: The TCP model which incorporates BED10 and tumor diameter indicates that radiobiological effect of target volume and dose calculation algorithm significantly affects TCP for lung SBRT patients. Dose calculation using MC-based algorithm is more realistic with tissue heterogeneities and is routinely performed in our clinic. Patients will be followed up to determine whether TCP prediction correlate clinical outcomes.
Purpose: To evaluate doses to the microscopic disease (MD) in adaptive radiotherapy (ART) for locally advanced non-small-cell lung cancer (NSCLC) and to model tumor control probability (TCP). Methods and Materials: In a retrospective planning study, three-dimensional conformal treatment plans for 13 patients with locally advanced NSCLC were adapted to shape and volume changes of the gross tumor volume (GTV) once or twice during conventionally fractionated radiotherapy with total doses of 66 Gy; doses in the ART plans were escalated using an iso-mean lung dose (MLD) approach compared to non-adapted treatment. Dose distributions to the volumes of suspect MD were simulated for a scenario with synchronous shrinkage of the MD and GTV and for a scenario of a stationary MD despite GTV shrinkage; simulations were performed using deformable image registration. TCP calculations considering doses to the GTV and MD were performed using three different models. Results: Coverage of the MD at 50 Gy was not compromised by ART. Coverage at 60 Gy in the scenario of a stationary MD was significantly reduced from 92% {+-} 10% to 73% {+-} 19% using ART; however, the coverage was restored by iso-MLD dose escalation. Dose distributions in the MD were sufficient to achieve a TCP >80% on average in all simulation experiments, with the clonogenic cell density the major factor influencing TCP. The combined TCP for the GTV and MD was 19.9% averaged over all patients and TCP models in non-adaptive treatment with 66 Gy. Iso-MLD dose escalation achieved by ART increased the overall TCP by absolute 6% (adapting plan once) and by 8.7% (adapting plan twice) on average. Absolute TCP values were significantly different between the TCP models; however, all TCP models suggested very similar TCP increase by using ART. Conclusions: Adaptation of radiotherapy to the shrinking GTV did not compromise dose coverage of volumes of suspect microscopic disease and has the potential to increase TCP by >40% compared with radiotherapy planning without ART.
Purpose: To determine how modelled maximum tumor control rates, achievable without exceeding mucositis tolerance (tcp{sub max-early}) vary with schedule duration for head and neck squamous cell carcinoma (HNSCC). Methods and materials: Using maximum-likelihood techniques, we have fitted a range of tcp models to two HNSCC datasets (Withers' and British Institute of Radiology [BIR]), characterizing the dependence of tcp on duration and equivalent dose in 2 Gy fractions (EQD{sub 2}). Models likely to best describe future data have been selected using the Akaike information criterion (AIC) and its quasi-AIC extension to overdispersed data. Setting EQD{sub 2}s in the selected tcp models to levels just tolerable for mucositis, we have plotted tcp{sub max-early} against schedule duration. Results: While BIR dataset tcp fits describe dose levels isoeffective for tumor control as rising significantly with schedule protraction, indicative of accelerated tumor repopulation, repopulation terms in fits to Withers' dataset do not reach significance after accounting for overdispersion of the data. The tcp{sub max-early} curves calculated from tcp fits to the overall Withers' and BIR datasets rise by 8% and 0-4%, respectively, between 20 and 50 days duration; likewise, tcp{sub max-early} curves calculated for stage-specific cohorts also generally rise slowly with increasing duration. However none of the increases in tcp{sub max-early} calculated from the overall or stage-specific fits reach significance. Conclusions: Local control rates modeled for treatments which lie just within mucosal tolerance rise slowly but insignificantly with increasing schedule length. This finding suggests that whereas useful gains may be made by accelerating unnecessarily slow schedules until they approach early reaction tolerance, little is achieved by shortening schedules further while reducing doses to remain within mucosal tolerance, an approach that may slightly worsen outcomes.
Purpose: Optimal treatment planning for fractionated external beam radiation therapy requires inputs from radiobiology based on recent thinking about the “five Rs” (repopulation, radiosensitivity, reoxygenation, redistribution, and repair). The need is especially acute for the newer, often individualized, protocols made feasible by progress in image guided radiation therapy and dose conformity. Current stochastic tumor control probability (TCP) models incorporating tumor repopulation effects consider “stem-like cancer cells” (SLCC) to be independent, but the authors here propose that SLCC-SLCC interactions may be significant. The authors present a new stochastic TCP model for repopulating SLCC interacting within microenvironmental niches. Our approach is meant mainly for comparing similar protocols. It aims at practical generalizations of previous mathematical models. Methods: The authors consider protocols with complete sublethal damage repair between fractions. The authors use customized open-source software and recent mathematical approaches from stochastic process theory for calculating the time-dependent SLCC number and thereby estimating SLCC eradication probabilities. As specific numerical examples, the authors consider predicted TCP results for a 2 Gy per fraction, 60 Gy protocol compared to 64 Gy protocols involving early or late boosts in a limited volume to some fractions. Results: In sample calculations with linear quadratic parameters α = 0.3 per Gy, α/β = 10 Gy, boosting is predicted to raise TCP from a dismal 14.5% observed in some older protocols for advanced NSCLC to above 70%. This prediction is robust as regards: (a) the assumed values of parameters other than α and (b) the choice of models for intraniche SLCC-SLCC interactions. However, α = 0.03 per Gy leads to a prediction of almost no improvement when boosting. Conclusions: The predicted efficacy of moderate boosts depends sensitively on α. Presumably, the larger values of α are the ones appropriate for individualized treatment protocols, with the smaller values relevant only to protocols for a heterogeneous patient population. On that assumption, boosting is predicted to be highly effective. Front boosting, apart from practical advantages and a possible advantage as regards iatrogenic second cancers, also probably gives a slightly higher TCP than back boosting. If the total number of SLCC at the start of treatment can be measured even roughly, it will provide a highly sensitive way of discriminating between various models and parameter choices. Updated mathematical methods for calculating repopulation allow credible generalizations of earlier results.
In the current study, boron doped biphasic calcium phosphate bioceramics consisting of a mixture of boron doped hydroxyapatite (BHA) and beta tricalcium phosphate (β-TCP) of varying BHA/β-TCP ratios were obtained after sintering stage. The effects of varying boron contents and different sintering temperatures on the BHA/β-TCP ratios and on the sinterability of the final products were investigated. Particle sizes and morphologies of the obtained precipitates were determined using SEM. XRD and FTIR investigation were conducted to detect the boron formation in the structure of HA and quantitative analysis was performed to determine the BHA/β-TCP ratio before and after sintering stage. In order to determine the sinterability of the obtained powders, pellets were prepared and sintered; the rates of densification were calculated and obtained results were correlated by SEM images. Also Vickers microhardness values of the sintered samples were determined. The experimental results verified that boron doped hydroxyapatite powders were obtained after sintering stage and the structure consists of a mixture of BHA and β-TCP. As the boron content used in the precipitation stage increases, β-TCP content of the BHA/β-TCP ratio increases but sinterability, density and microhardness deteriorate. As the sintering temperature increases, β-TCP content, density and microhardness of the samples increase and sinterability improves. - Highlights: • This is the first paper about boron doped biphasic calcium phosphate bioceramics. • Boron doping affects the structural and mechanical properties. • BHA/β-TCP ratio can be adjustable with boron content and sintering temperature.
We study a dynamically asymmetric binary glass former with the low-T{sub g} component m-tri-cresyl phosphate (m-TCP: T{sub g} = 206 K) and a spirobichroman derivative as a non-polymeric high-T{sub g} component (T{sub g} = 382 K) by means of {sup 1}H nuclear magnetic resonance (NMR), {sup 31}P NMR, and dielectric spectroscopy which allow component-selectively probing the dynamics. The entire concentration range is covered, and two main relaxation processes with two T{sub g} are identified, T{sub g1} and T{sub g2}. The slower one is attributed to the high-T{sub g} component (α{sub 1}-process), and the faster one is related to the m-TCP molecules (α{sub 2}-process). Yet, there are indications that a small fraction of m-TCP is associated also with the α{sub 1}-process. While the α{sub 1}-relaxation only weakly broadens upon adding m-TCP, the α{sub 2}-relaxation becomes extremely stretched leading to quasi-logarithmic correlation functions at low m-TCP concentrations—as probed by {sup 31}P NMR stimulated echo experiments. Frequency-temperature superposition does not apply for the α{sub 2}-process and it reflects an isotropic, liquid-like motion which is observed even below T{sub g1}, i.e., in the matrix of the arrested high-T{sub g} molecules. As proven by 2D {sup 31}P NMR, the corresponding dynamic heterogeneities are of transient nature, i.e., exchange occurs within the distribution G(lnτ{sub α2}). At T{sub g1} a crossover is found for the temperature dependence of (mean) τ{sub α2}(T) from non-Arrhenius above to Arrhenius below T{sub g1} which is attributed to intrinsic confinement effects. This “fragile-to-strong” transition also leads to a re-decrease of T{sub g2}(c{sub m−TCP}) at low concentration c{sub m−TCP}, i.e., a maximum is observed in T{sub g2}(c{sub m−TCP}) while T{sub g1}(c{sub m−TCP}) displays the well-known plasticizer effect. Although only non-polymeric components are involved, we re-discover essentially all features previously reported for polymer-plasticizer systems.
Purpose: Tumors are composed of a large number of clonogens that have the capability of indefinite reproduction. Even when there is complete clinical or radiographic regression of the gross tumor mass after treatment, tumor recurrence can occur if the clonogens are not completely eradicated by radiotherapy. This study was to investigate the colonogen number and its association with the tumor control probability (TCP) in oropharyngeal squamous cell carcinoma (OSCCA). Methods: A literature search was conducted to collect clinical information of patients with OSCCA, including the prescription dose, tumor volume and survival rate. The linear-quadratic (LQ) model was incorporated into TCP model for clinical data analysis. The total dose ranged from 60 to 70 Gy and tumor volume ranged from 10 to 50 cc. The TCP was calculated for each group according to tumor size and dose. The least χ{sup 2} method was used to fit the TCP calculation to clinical data while other LQ model parameters (α, β) were adopted from the literature, due to the limited patient data. Results: A total of 190 patients with T2–T4 OSCCA were included. The association with HPV was not available for all the patients. The 3-year survival rate was about 82% for T2 squamous cell carcinoma and 40% for advanced tumors. Fitting the TCP model to the survival data, the average clonogen number was 1.56×10{sup 12}. For the prescription dose of 70 Gy, the calculated TCP ranged from 40% to 90% when the tumor volume varied from 10 to 50 cc. Conclusion: Our data suggests variation between the clonogen number and TCP in OSCCA. Tumors with larger colonogen number tend to have lower TCP and therefore dose escalation above 70 Gy may be indicated in order to improve the TCP and survival rate. Our result will require future confirmation with a large number of patients.
Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using {sup 11}C-choline positron emission tomography PET scans in patients with localized prostate cancer. Methods and Materials: This was an RT planning study of 8 patients with prostate cancer who had {sup 11}C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV{sub 60%} and SUV{sub 70%}). Three IMRT plans were generated for each patient: PLAN{sub 78}, which consisted of whole-prostate radiation therapy to 78 Gy; PLAN{sub 78-90}, which consisted of whole-prostate RT to 78 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy; and PLAN{sub 72-90}, which consisted of whole-prostate RT to 72 Gy, a boost to the SUV{sub 60%} to 84 Gy, and a further boost to the SUV{sub 70%} to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP{sub PET}) and on prostatectomy-defined volumes (TCP{sub path}), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. Results: All plans for all patients reached prescription doses while adhering to dose constraints. TCP{sub PET} values for PLAN{sub 78}, PLAN{sub 78-90}, and PLAN{sub 72-90} were 65%, 97%, and 96%, respectively. TCP{sub path} values were 71%, 97%, and 89%, respectively. Both PLAN{sub 78-90} and PLAN{sub 72-90} had significantly higher TCP{sub PET} (P=.002 and .001) and TCP{sub path} (P<.001 and .014) values than PLAN{sub 78}. PLAN{sub 78-90} and PLAN{sub 72-90} were not significantly different in terms of TCP{sub PET} or TCP{sub path}. There were no significant differences in rectal NTCPs between the 3 plans. Conclusions: IMRT dose painting for localized prostate cancer using {sup 11}C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.
The purpose of this work was to compare static gantry intensity-modulated radiation therapy (IMRT) with volume-modulated arc therapy (VMAT) in terms of tumor control probability (TCP) under scenarios involving large geometric misses, i.e., those beyond what are accounted for when margin expansion is determined. Using a planning approach typical for these treatments, a linear-quadratic–based model for TCP was used to compare mean TCP values for a population of patients who experiences a geometric miss (i.e., systematic and random shifts of the clinical target volume within the planning target dose distribution). A Monte Carlo approach was used to account for the different biological sensitivities of a population of patients. Interestingly, for errors consisting of coplanar systematic target volume offsets and three-dimensional random offsets, static gantry IMRT appears to offer an advantage over VMAT in that larger shift errors are tolerated for the same mean TCP. For example, under the conditions simulated, erroneous systematic shifts of 15 mm directly between or directly into static gantry IMRT fields result in mean TCP values between 96% and 98%, whereas the same errors on VMAT plans result in mean TCP values between 45% and 74%. Random geometric shifts of the target volume were characterized using normal distributions in each Cartesian dimension. When the standard deviations were doubled from those values assumed in the derivation of the treatment margins, our model showed a 7% drop in mean TCP for the static gantry IMRT plans but a 20% drop in TCP for the VMAT plans. Although adding a margin for error to a clinical target volume is perhaps the best approach to account for expected geometric misses, this work suggests that static gantry IMRT may offer a treatment that is more tolerant to geometric miss errors than VMAT.
Purpose: The tumor control probability in radiation therapy allows comparing different radiation treatments to each other by means of calculating the probability that a prescribed dose of radiation eradicates or controls the tumor. In the conventional approach, all cancer cells can divide unlimited number of times and the tumor control often means eradicating every malignant cell by the radiation. In recent years however, there is a mounting consensus that in a given tumor volume there is a sub-population of cells, known as cancer stem cells (CSCs) that are responsible for tumor initiation and growth. Other or progenitor cancer cells can only divide limited number of times. This entails that only cancer stem cells may nned to be eliminated in order to control the tumor. Thus one may define TCP as the probability of eliminating CSCs for the given dose of radiation. Methods: Using stochastic methods, specifically the birth-and-death Markov processes, an infinite system of equations is set for probabilities of having m cancer stem cells at time t after the start of radiation. The TCP is calculated as the probability of no cancer stem cells surviving the radiation. Two scenarios are studied. In the first situation, the TCP is calculated for a unidirectional case when CSC gives birth to another CSC or a progenitor cell. In the second scenario, a bidirectional model is studied where the progenitor cell gives rise to CSC. Results: The proposed calculations show that the calculated TCP for CSC depends on whether one adopts unidirectional or bidirectional conversion models. The bidirectional model shows significantly lower TCP values for the given dose delivered to the tumor. Conclusion: Incorporating CSC hypothesis into the TCP modeling may notably influence the dose prescription as well as the concept of the expected TCP after the radiation treatments.