Off-line Protocol Research Articles

Transition of May Measurement Month to an online hypertension awareness campaign in Korea during the COVID-19 pandemic.

Aims May Measurement Month (MMM) is a global campaign to enhance hypertension awareness by intensive blood pressure measuring campaign during a month period of May. May Measurement Month 2020 was not officially executed globally, especially in light of COVID-19 pandemic. But in Korea, the MMM committee decided to carry on with self-initiated project to succeed MMM started in 2019 in Korea. And we adopted new online strategies for those with age of 18 or older under the MMMMethods and results Korea 2020 theme in Korean of ‘Look for the Young Hypertension’. A promotional video, a subtitled translated global promotional video, and four educational contents were uploaded on Youtube®. Seven online posters or card news were uploaded on main blog. And 71 articles by 60 websites from 10 medical media company were published. The MMM keyword exposure in Naver® portal Search Advertisements was 2500 searches per day. There were 3519 visits to the MMM blog, and 114 people participated in snapshot challenges. Four social network service channels were activated, and there was an increase in Facebook and Instagram followers of 6.5- and 5.8-fold, respectively. GoodDoc® application programming interface messages were sent 97876 times (2589 responses). For a user created contents contest, 28 competitors, mostly young, participated.Conclusion Even during the COVID-19 pandemic, the MMM campaign was able to survive using a ‘new normal’ online format. The shift to on-line activity during the pandemic will contribute to a breakthrough MMM campaign in the future that can be combined with off-line protocols even after the pandemic.

Prospective observational study to estimate set-up errors and optimise PTV margins in patients undergoing IMRT for head and neck cancers from a Government cancer centre of Eastern India

AbstractBackground:The head and neck cancers as a whole are the most common cancers among males in India. Technological advancements have led to an improvement in radiation therapy (RT) techniques with subsequent reduction in normal tissue complications. To correct patient set-up errors, an off-line correction method like no action level (NAL) protocol may be used as a preferred protocol particularly for a busy department. The objectives of the study were to measure the translational set-up errors using kV cone-beam computed tomography (CBCT) in patients undergoing intensity modulated radiotherapy (IMRT) in head and neck cancers and also to optimise clinical target volume (CTV) to planning target volume (PTV) margin using NAL protocol.Material and methods:On the first 5 days of RT, patient’s position was verified by kV-CBCT and then weekly during the course of treatment. The comparison between the reference and kV-CBCT images was performed, and the shifts measured and recorded. The mean error from the initial five consecutive fractions was corrected on the sixth daily fraction. Displacements in all the directions were measured. The population systematic and random errors were determined and used to estimate PTV margins according to the van Herk formula.Results:A total of 322 images were analysed. Before correction, 15, 12 and 9% patients had systematic error ≥3 mm on X, Y and Z axes, but after correction this was reduced to 9, 0 and 0%. The total percentage of patients whose set-up margin was ≥5 mm before correction was 5, 6·25, 3·75%, but after correction it reduced to 1·88, 0, and 0·63%. The margins of total population were reduced to 63, 65 and 56% after correction on X, Y and Z axes, respectively.Conclusion:A simple off-line NAL protocol can correct the set-up errors without daily on-line imaging in patients undergoing IMRT and hence acting as a resource sparing alternative. Five millimetre margin to CTVs was adequate and safe to overcome the problem of set-up errors in head and neck IMRT.

Technical Note: Scintillation well counters and particle counting digital autoradiography devices can be used to detect activities associated with genomic profiling adequacy of biopsy specimens obtained after a low activity 18 F-FDG injection.

Genomic profiling of biopsied tissue is the basis for precision cancer therapy. However, biopsied materials may not contain sufficient amounts of tumor deoxyribonucleonic acid needed for the analysis. We propose a method to determine the adequacy of specimens for performing genomic profiling by quantifying their metabolic activity. We estimated the average density of tumor cells in biopsy specimens needed to successfully perform genomic analysis following the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) protocol from the minimum amount of deoxyribonucleonic acid needed and the volume of tissue typically used for analysis. The average 18 F-FDG uptake per cell was assessed by incubating HT-29 adenocarcinoma tumor cells in 18 F-FDG containing solution and then measuring their activity with a scintillation well counter. Consequently, we evaluated the response of two devices around the minimum expected activities which would indicate genomic profiling adequacy of biopsy specimens obtained under 18 F-FDG PET/CT guidance. Surrogate samples obtained using 18G core needle biopsies of gels containing either 18 F-FDG-loaded cells in the expected concentrations or the corresponding activity were measured using autoradiography and a scintillation well counter. Autoradiography was performed using a CCD-based device with real-time image display as well as with digital autoradiography imaging plates following a 30-min off-line protocol for specimen activity determination against previously established calibration. Cell incubation experiments and estimates obtained from quantitative autoradiography of biopsy specimens (QABS) indicate that specimens acquired under 18 F-FDG PET/CT guidance that contained the minimum amount of cells needed for genomic profiling would have an average activity concentration in the range of about 3 to about 9 kBq/mL. When exposed to specimens with similar activity concentration, both a CCD-based autoradiography device and a scintillation well counter produced signals with sufficient signal-to-background ratio for specimen genomic adequacy identification in less than 10 min, which is short enough to allow procedure guidance. Scintillation well counter measurements and CCD-based autoradiography have adequate sensitivity to detect the tumor burden needed for genomic profiling during 18 F-FDG PET/CT-guided 18G core needle biopsies of liver adenocarcinoma metastases.

Enzymatic Reactor with Trypsin Immobilized on Graphene Oxide Modified Polymer Microspheres To Achieve Automated Proteome Quantification.

Protein digestion and isotope labeling are two critical steps in proteome quantification. However, the conventional in-solution protocol unavoidably suffers from disadvantages such as time-consuming, low labeling efficiency, and tedious off-line manual operation, which might affect the quantification accuracy, reproducibility, and throughput. To address these problems, we developed a fully automated proteome quantification platform, in which an ultraperformance immobilized microreactor (upIMER) with graphene-oxide-modified polymer microspheres as the matrix was developed, to achieve not only the simultaneous protein digestion and 18O labeling, but also the online integration with nano-high-pressure liquid chromatography-electrospray ionization-tandem mass spectrometry (nanoHPLC-ESI-MS/MS). Compared to the conventional off-line protocols, such a platform exhibits obviously improved digestion and 18O labeling efficiency (only 8% peptides with missed cleavage sites, 99% labeling efficiency, and 2.5 min reaction time), leading to the increased quantification coverage, accuracy, precision and throughput. All the results demonstrated that our developed fully automated platform should provide new opportunities to improve the accuracy, reproducibility, and throughput for proteome quantification.

M&E-NetPay: A Micropayment System for Mobile and Electronic Commerce

As an increasing number of people purchase goods and services online, micropayment systems are becoming particularly important for mobile and electronic commerce. We have designed and developed such a system called M&E-NetPay (Mobile and Electronic NetPay). With open interoperability and mobility, M&E-NetPay uses web services to connect brokers and vendors, providing secure, flexible and reliable credit services over the Internet. In particular, M&E-NetPay makes use of a secure, inexpensive and debit-based off-line protocol that allows vendors to interact only with customers, after validating coins. The design of the architecture and protocol of M&E-NetPay are presented, together with the implementation of its prototype in ringtone and wallpaper sites. To validate our system, we have conducted its evaluations on performance, usability and heuristics. Furthermore, we compare our system to the CORBA-based (Common Object Request Broker Architecture) off-line micro-payment systems. The results have demonstrated that M&E-NetPay outperforms the .NET-based M&E-NetPay system in terms of performance and user satisfaction.

Global sensitivity analysis of a filtration model for submerged anaerobic membrane bioreactors (AnMBR)

The results of a global sensitivity analysis of a filtration model for submerged anaerobic MBRs (AnMBRs) are assessed in this paper. This study aimed to (1) identify the less- (or non-) influential factors of the model in order to facilitate model calibration and (2) validate the modelling approach (i.e. to determine the need for each of the proposed factors to be included in the model). The sensitivity analysis was conducted using a revised version of the Morris screening method. The dynamic simulations were conducted using long-term data obtained from an AnMBR plant fitted with industrial-scale hollow-fibre membranes. Of the 14 factors in the model, six were identified as influential, i.e. those calibrated using off-line protocols. A dynamic calibration (based on optimisation algorithms) of these influential factors was conducted. The resulting estimated model factors accurately predicted membrane performance.

Cone Beam CT (CBCT) Guided Tumor Positioning for Laryngeal Cancer Patients With Large Interfraction Time Trends in Tumor Setup

Comparing CBCT guided set-up correction protocols for laryngeal cancer patients with large interfraction time trends in primary tumor set-up relative to the treatment isocenter. For 30 laryngeal cancer patients (2 T1, 7 T2, 16 T3, 5 T4), cone beam CT measured displacements in the fractionated treatments were used to establish residual set-up errors for 1) the No Action Level (NAL) off-line protocol: CBCT only acquired in the first 3 fractions, mean displacement vector in these fractions used for corrections in all later fractions, 2) extended NAL (eNAL): NAL with weekly follow-up CBCT for weekly adjustment of the correction vector, and 3) daily CBCT acquisition with on-line analysis and patient re-positioning prior to dose delivery. Without set-up corrections, large Superior-Inferior (SI) interfraction time trends in primary tumor set-up would have occurred (46% of patients ≥ 8 mm/7 weeks). Because of the trends, application of the often used NAL would have led to large residual errors (required SI margin around the primary tumor: 6.7 mm). Due to the weekly correction vector adjustments, the trends could be largely compensated with eNAL (SI margin 3.5 mm). Correlation between movements of the primary and nodal CTVs in SI direction was poor (r2 = 0.15). For this reason, even with perfect on-line set-up corrections of the primary CTV (no residual errors), the required SI margin for the nodal CTV would be as large as 7 mm. In Left-Right (LR) and Anterior-Posterior (AP) directions, movements of the primary and nodal CTVs were largely correlated (r2 = 071/0.64). Even with the two off-line protocols, required PTV margins in LR and AP directions were limited to 2-3 mm for both CTVs. SI motion correlation between the cervical vertebrae and the primary CTV was poor ((r2 = 0.19). When using the vertebrae as reference structure in image guidance, the required SI margin around the primary CTV would be 7 mm, even with daily on-line repositioning. Without set-up corrections, laryngeal cancer patients showed large SI interfraction time trends in set-up of the primary tumor that could partially or almost fully be compensated with eNAL and daily on-line, respectively. Due to poor SI motion correlation of the primary tumor and the nodes, even perfect daily repositioning of the primary CTV required a 7 mm PTV margin around the nodes. Small nodal PTV margins would require an adaptive approach to correct for the non-rigid motion. Even with daily on-line corrections, the required SI PTV margin around the primary CTV would be as large as 7 mm, when using the vertebrae as reference structure in image guidance. Generally applied 5 mm PTV margins in head and neck cancer were often inadequate for the studied laryngeal cancer patients.

Radiation Treatment of T1-T2N0 Squamous Cell Carcinoma of the Glottic Larynx in the Modern Era

adjustments, the trends could be largely compensated with eNAL (SI margin 3.5 mm). Correlation between movements of the primary and nodal CTVs in SI direction was poor (r Z 0.15). For this reason, even with perfect on-line set-up corrections of the primary CTV (no residual errors), the required SI margin for the nodal CTV would be as large as 7 mm. In Left-Right (LR) and Anterior-Posterior (AP) directions, movements of the primary and nodal CTVs were largely correlated (r Z 071/0.64). Even with the two off-line protocols, required PTV margins in LR and AP directions were limited to 2-3 mm for both CTVs. SI motion correlation between the cervical vertebrae and the primary CTV was poor ((r Z 0.19). When using the vertebrae as reference structure in image guidance, the required SI margin around the primary CTV would be 7 mm, even with daily on-line repositioning. Conclusions: Without set-up corrections, laryngeal cancer patients showed large SI interfraction time trends in set-up of the primary tumor that could partially or almost fully be compensated with eNAL and daily on-line, respectively. Due to poor SI motion correlation of the primary tumor and the nodes, even perfect daily repositioning of the primary CTV required a 7 mm PTV margin around the nodes. Small nodal PTV margins would require an adaptive approach to correct for the non-rigid motion. Even with daily online corrections, the required SI PTVmargin around the primary CTVwould be as large as 7mm, when using the vertebrae as reference structure in image guidance. Generally applied 5 mm PTV margins in head and neck cancer were often inadequate for the studied laryngeal cancer patients. Author Disclosure: B. Heijmen: None. A. Gangsaas: None. E. Astreinidou: None. S. Quint: None. P. Levendag: None.

Adaptive off-line protocol for prostate external radiotherapy with cone beam computer tomography

The goal of this work was to prepare and to evaluate an off-line adaptive protocol for prostate teleradiotherapy with kilovoltage cone beam computer tomography (CBCT). Ten patients with localized prostate carcinoma treated with external beams underwent image-guided radiotherapy. In total, 162CBCT images were collected. Position of prostate and pubis symphysis (PS) with respect to the isocenter were measured off-line. Using the CBCT scans obtained in the first three fractions the average position of prostate in relation (AvPosPr) to PB was calculated. On each CBCT scan, the position of prostate with respect to AvPosPr was calculated and cumulative histogram of prostate displacement with respect to AvPosPr was prepared. Using this data, the adaptive protocol was prepared in which (1) based on the CBCT made in the first three fractions the AvPosPr to PS is obtained, (2) in all other fractions two orthogonal images are acquired and if for any direction set-up error exceeds 0.2cm the patient's position is corrected, and (3) additionally, the patient's position is corrected if the AvPosPr exceeds 0.2cm in any direction. To evaluate the adaptive protocol for 30consecutive patients, the CBCT was also made in 10th and 21st fraction. For the first 10patients, the results revealed that the prostate was displaced in relation to AvPosPr >0.7cm in the vertical and longitudinal directions only on 4 and 5images of 162CBCT images, respectively. For the lateral direction, this displacement was >0.3cm in one case. For the group of 30patients, displacement was never >0.7, and 0.3cm for the vertical and lateral directions. In two cases, displacements were >0.7cm for the longitudinal direction. Implementation of the proposed adaptive procedure based on the on-line set-up error elimination followed by a reduction of systematic internal error enables reducing the CTV-PTV margin to 0.7, 0.7, and 0.4cm for the vertical, longitudinal, and lateral directions, respectively.

A study of respiration‐correlated cone‐beam CT scans to correct target positioning errors in radiotherapy of thoracic cancer

There is increasingly widespread usage of cone-beam CT (CBCT) for guiding radiation treatment in advanced-stage lung tumors, but difficulties associated with daily CBCT in conventionally fractionated treatments include imaging dose to the patient, increased workload and longer treatment times. Respiration-correlated cone-beam CT (RC-CBCT) can improve localization accuracy in mobile lung tumors, but further increases the time and workload for conventionally fractionated treatments. This study investigates whether RC-CBCT-guided correction of systematic tumor deviations in standard fractionated lung tumor radiation treatments is more effective than 2D image-based correction of skeletal deviations alone. A second study goal compares respiration-correlated vs respiration-averaged images for determining tumor deviations. Eleven stage II-IV nonsmall cell lung cancer patients are enrolled in an IRB-approved prospective off-line protocol using RC-CBCT guidance to correct for systematic errors in GTV position. Patients receive a respiration-correlated planning CT (RCCT) at simulation, daily kilovoltage RC-CBCT scans during the first week of treatment and weekly scans thereafter. Four types of correction methods are compared: (1) systematic error in gross tumor volume (GTV) position, (2) systematic error in skeletal anatomy, (3) daily skeletal corrections, and (4) weekly skeletal corrections. The comparison is in terms of weighted average of the residual GTV deviations measured from the RC-CBCT scans and representing the estimated residual deviation over the treatment course. In the second study goal, GTV deviations computed from matching RCCT and RC-CBCT are compared to deviations computed from matching respiration-averaged images consisting of a CBCT reconstructed using all projections and an average-intensity-projection CT computed from the RCCT. Of the eleven patients in the GTV-based systematic correction protocol, two required no correction, seven required a single correction, one required two corrections, and one required three corrections. Mean residual GTV deviation (3D distance) following GTV-based systematic correction (mean ± 1 standard deviation 4.8 ± 1.5 mm) is significantly lower than for systematic skeletal-based (6.5 ± 2.9 mm, p = 0.015), and weekly skeletal-based correction (7.2 ± 3.0 mm, p = 0.001), but is not significantly lower than daily skeletal-based correction (5.4 ± 2.6 mm, p = 0.34). In two cases, first-day CBCT images reveal tumor changes-one showing tumor growth, the other showing large tumor displacement-that are not readily observed in radiographs. Differences in computed GTV deviations between respiration-correlated and respiration-averaged images are 0.2 ± 1.8 mm in the superior-inferior direction and are of similar magnitude in the other directions. An off-line protocol to correct GTV-based systematic error in locally advanced lung tumor cases can be effective at reducing tumor deviations, although the findings need confirmation with larger patient statistics. In some cases, a single cone-beam CT can be useful for assessing tumor changes early in treatment, if more than a few days elapse between simulation and the start of treatment. Tumor deviations measured with respiration-averaged CT and CBCT images are consistent with those measured with respiration-correlated images; the respiration-averaged method is more easily implemented in the clinic.

Fluorescence-based tools to improve biopharmaceutical process development

Background Process optimization and control are essential to match biopharmaceutical market demands. Early-steps in the development of new processes require screening hundreds of transfected clones in order to select those with the best expression characteristics, and identifying optimal environmental conditions for these clones to grow and express the protein of interest. While some culture systems include in situ analysis of cell density, most often by optical density or capacitance measurements, the majority of them still rely on off-line, laborious and time-consuming protocols for recombinant protein analysis. Spectroscopic methods have been proposed in literature to support bioprocesses development, because they are non-invasive and provide data on multiple components present in the culture bulks, thereby increasing information on process performance [1]. Here, we developed a fluorescence-based method for real-time monitoring of viable cells and antibody titers in bioreactor cultures, and extended this strategy for high throughput analysis of cellular productivity in 96well plates.

The reliability of proton-nuclear interaction cross-section data to predict proton-induced PET images in proton therapy

In vivo PET range verification relies on the comparison of measured and simulated activity distributions. The accuracy of the simulated distribution depends on the accuracy of the Monte Carlo code, which is in turn dependent on the accuracy of the available cross-section data for β+ isotope production. We have explored different cross-section data available in the literature for the main reaction channels (16O(p,pn)15O, 12C(p,pn)11C and 16O(p,3p3n)11C) contributing to the production of β+ isotopes by proton beams in patients. Available experimental and theoretical values were implemented in the simulation and compared with measured PET images obtained with a high-resolution PET scanner. Each reaction channel was studied independently. A phantom with three different materials was built, two of them with high carbon or oxygen concentration and a third one with average soft tissue composition. Monoenergetic and SOBP field irradiations of the phantom were accomplished and measured PET images were compared with simulation results. Different cross-section values for the tissue-equivalent material lead to range differences below 1 mm when a 5 min scan time was employed and close to 5 mm differences for a 30 min scan time with 15 min delay between irradiation and scan (a typical off-line protocol). The results presented here emphasize the need of more accurate measurement of the cross-section values of the reaction channels contributing to the production of PET isotopes by proton beams before this in vivo range verification method can achieve mm accuracy.

Correction of systematic set-up error in breast and head and neck irradiation through a no-action level (NAL) protocol

To quantify systematic and random patient set-up errors in breast and head and neck conventional irradiation and to evaluate a no-action level (NAL) protocol for systematic set-up error off-line correction in head and neck cancer and breast cancer patients. Verification electronic portal images of orthogonal set-up fields were obtained daily for the initial four consecutive fractions for 20 patients treated for breast cancer and for 20 head and neck cancer patients. The calculated systematic error was used to shift the isocentre accordingly on the fifth treatment day. From then until the end of the treatment course, pair orthogonal portal images of set-up fields were obtained weekly. To assess the impact of the protocol, pre- and post-correction systematic errors were compared and PTV margins were estimated before and after correction using published margin recipes. Population systematic set-up error decreased in the breast cancer patient group after the implementation of NAL protocol from 4.0 to 1.7 mm on the x-axis, from 4.7 to 2.1 mm on the y-axis and from 2.8 to 0.9 mm on the z axis. The percentage of patients with individual systematic set-up error reduction was 80%, 90% and 80% on the x-, y and z-axes respectively. Population systematic set-up error decreased also in the head and neck cancer patient group from 2.3 to 1.1 mm on the x-axis, from 1.6 to 1.4 mm on the y-axis and from 1.7 to 0.7 mm on the z-axis. The percentage of patients with individual systematic set-up error reduction was 70%, 65% and 85% on the x-, y- and z-axes respectively. Margin reduction achievable with NAL protocol implementation on the x-, y- and z-axes was 6.3, 7.2 and 4.8 mm for breast cancer patients and 3.3, 0.6 and 2.8 mm for head and neck cancer patients. NAL off-line protocol is useful for systematic set-up error correction and PTV margin reduction in conventional breast and head and neck irradiation.

Comparison of prostate set‐up accuracy and margins with off‐line bony anatomy corrections and online implanted fiducial‐based corrections

The aim of the study was to determine prostate set-up accuracy and set-up margins with off-line bony anatomy-based imaging protocols, compared with online implanted fiducial marker-based imaging with daily corrections. Eleven patients were treated with implanted prostate fiducial markers and online set-up corrections. Pretreatment orthogonal electronic portal images were acquired to determine couch shifts and verification images were acquired during treatment to measure residual set-up error. The prostate set-up errors that would result from skin marker set-up, off-line bony anatomy-based protocols and online fiducial marker-based corrections were determined. Set-up margins were calculated for each set-up technique using the percentage of encompassed isocentres and a margin recipe. The prostate systematic set-up errors in the medial-lateral, superior-inferior and anterior-posterior directions for skin marker set-up were 2.2, 3.6 and 4.5 mm (1 standard deviation). For our bony anatomy-based off-line protocol the prostate systematic set-up errors were 1.6, 2.5 and 4.4 mm. For the online fiducial based set-up the results were 0.5, 1.4 and 1.4 mm. A prostate systematic error of 10.2 mm was uncorrected by the off-line bone protocol in one patient. Set-up margins calculated to encompass 98% of prostate set-up shifts were 11-14 mm with bone off-line set-up and 4-7 mm with online fiducial markers. Margins from the van Herk margin recipe were generally 1-2 mm smaller. Bony anatomy-based set-up protocols improve the group prostate set-up error compared with skin marks; however, large prostate systematic errors can remain undetected or systematic errors increased for individual patients. The margin required for set-up errors was found to be 10-15 mm unless implanted fiducial markers are available for treatment guidance.

Experiences at the Paul Scherrer Institute With a Remote Patient Positioning Procedure for High-Throughput Proton Radiation Therapy

To describe a remote positioning system for accurate and efficient proton radiotherapy treatments. To minimize positioning time in the treatment room (and thereby maximize beam utility), we have adopted a method for remote patient positioning, with patients positioned and imaged outside the treatment room. Using a CT scanner, positioning is performed using orthogonal topograms with the measured differences to the reference images being used to define daily corrections to the patient table in the treatment room. Possible patient movements during transport and irradiation were analyzed through periodic acquisition of posttreatment topograms. Systematic and random errors were calculated for this daily positioning protocol and for two off-line protocols. The potential time advantage of remote positioning was assessed by computer simulation. Applying the daily correction protocol, systematic errors calculated over all patients (n = 94) were below 0.6 mm, whereas random errors were below 1.5 mm and 2.5 mm, respectively, for bite-block and for mask immobilization. Differences between pre- and posttreatment images were below 2.8 mm (SD) in abdominal/pelvic region, and below 2.4 mm (SD) in the head. Retrospective data analysis for a subset of patients revealed that off-line protocols would be significantly less accurate. Computer simulations showed that remote positioning can increase patient throughput up to 30%. The use of a daily imaging and correction protocol based on a "remote" CT could reduce positioning errors to below 2.5 mm and increase beam utility in the treatment room. Patient motion between imaging and treatment were not significant.

Evaluation of a Motion-Encompassing Treatment Strategy for Treating Non-Small Cell Lung Cancer

This study analyzes the setup error of a motion-encompassing treatment strategy for treating non-small cell lung cancer. Using data from patients who were treated with daily KV cone-beam CT (CBCT) image-guidance (IG) for setup correction, the residual setup errors for a hybrid off-line IG protocol were assessed. 22 patients with NSCLC were treated with a motion-encompassing daily CBCT IG strategy during 4/2006 to 3/2007. 4D-CT imaging was used for treatment planning. Patients were scanned in the supine position during normal relaxed free-breathing and were immobilized with a wing-board. The internal target volume (ITV) was determined using the maximum-intensity-projection (MiP) CT data to account for organ motion. A 5-mm PTV margin was used to account for setup error. On-line setup correction was based on the daily CBCT imaging prior to treatment, with an action level of 3 mm. The systematic and random errors were analyzed retrospectively. The results were then fit to a hybrid off-line IG strategy where the patient underwent CBCT-IG for the first 4 fractions. The treatment setup was corrected on-line if the setup error exceeded the action level of 3 mm. A mean shift was then applied on the 5th and the subsequent fractions to correct for the systematic error. The residual errors of the hybrid off-line protocols were assessed. The systematic and random errors were found to be 5.2 ± 3.2 mm, 4.4 ± 2.7 mm and 4.4 ± 3.4 mm for anterior-posterior (AP), medial-lateral (ML) and superior-inferior (SI) directions respectively. The 3D displacement vectors (DV) were 9.9 mm ± 4.7 mm (systematic ± random). The residual error was within 2 mm in all directions for the daily IG strategy. For the hybrid off-line IG strategy, the frequency of the residual errors is shown in the figure. The occurrence frequency was 61% for the 5-mm DV, indicating that the hybrid off-line IG strategy was inadequate. The use of a 5 mm PTV margin on the ITV determined by MiP dataset combined with daily CBCT on-line correction is adequate to avoid geometric miss of the tumor for NSCLC patients. However, the hybrid off-line IG strategy is inadequate unless a larger PTV margin is used.

Fatty acid profiling of raw human plasma and whole blood using direct thermal desorption combined with gas chromatography–mass spectrometry

Gas chromatography (GC) has in recent times become an important tool for the fatty acid profiling of human blood and plasma. An at-line procedure used in the fatty acid profiling of whole/intact aquatic micro-organisms without any sample preparation was adapted for this work. A direct thermal desorption (DTD) interface was used to profile the fatty acid composition of human plasma and whole human blood of eight volunteers in a procedure omitting the usual lipid extraction steps that precede sample methylation in the traditional (off-line) protocols. Trimethylsulfonium hydroxide (TMSH) was used as reagent for thermally assisted methylation. In a fully automated manner, the liner of the GC injector is used as a sample-and-reaction container with the aid of the DTD interface. The fatty acid methyl ester (FAME) profiles obtained using this novel approach, were very identical to those obtained when the traditional off-line protocol was applied. FAME yields obtained in the at-line DTD method were found to be very similar for saturated fatty acids, but significantly higher for polyunsaturated fatty acids compared to off-line yields. As a result of the contribution of circulating cell membranes in blood, substantial differences were observed when the amount of FAMEs obtained in whole human blood and human plasma samples were compared after their analysis. Thanks to the fully automated operation of this novel procedure, large series of analyses can easily be performed.

An integrated energy aware wireless transmission system for QoS provisioning in wireless sensor network

A significant amount of research efforts have been done to improve the energy efficiency of wireless sensor network (WSN). However, not much has been done to optimize the Quality of Services (QoS) of WSN. Actually, energy efficiency should be jointly optimized with QoS to make WSN useful. In this paper, we develop an integrated adaptive wireless transmission system for WSN to meet the QoS requirements in an energy-aware fashion. The QoS requirements in the application layer, the modulation and transmission schemes in the data link layer and physical layer are jointly analyzed and integrated into a single framework. In this framework, the cluster-based protocol is used, where the cluster heads form a multi-hop backbone. The intra-cluster QoS performance and inter-cluster QoS performance are both analyzed. Based on the results, the overall energy consumption and QoS in terms of BER performance, end-to-end transmission latency and packet loss ratio are modelled by the communication parameters of the cluster heads including the modulation level (bits per symbol) and transmit power. According to the model, a centralized off-line protocol is designed in the integrated framework to adjust the communication parameters of the cluster heads for fixed QoS provisioning. And a distributed online protocol is also designed for dynamic QoS provisioning. Extensive simulation results under various experimental settings demonstrate the energy-saving performance of the proposed integrated system. The ability to adapt to time-varying delivery quality requirements is also tested.

Correction of systematic setup errors in prostate radiation therapy: How many images to perform?

The purpose of this study was to develop an evidence-based off-line setup correction protocol for systematic errors in prostate radiation therapy. Daily orthogonal electronic portal images were acquired from 30 patients. Field displacements were measured in the medial-lateral (ML), superior-inferior (SI), and anterior-posterior (AP) directions for each treatment fraction. The off-line protocol corrects the mean field displacement found from n consecutive images, starting at a particular fraction of treatment, with a fixed tolerance level. Simulations were performed with the measured data to determine (1) how many images (n) should be averaged to determine the systematic error; (2) on which treatment fraction should the protocol be initiated; and (3) what tolerance level should be applied to determine whether the patient position should be corrected. Uncorrected systematic errors in the ML, SI, and AP directions were (mean position +/- 1 standard deviation [SD]): -0.7 +/- 2.2 mm, -1.5 +/- 1.3 mm, and 1.4 +/- 2.6 mm, respectively. Random errors (1 SD and range) were 1.9 mm (1.3 - 3.3), 1.5 mm (0. - 4.1), and 1.8 mm (1.0-2.6), respectively. A correction based on a single image taken on the first fraction actually increased the systematic errors in the ML and SI directions compared with no correction. More accurate correction of systematic errors was achieved with increasing number of images averaged, with only small benefit after 5 images. With fewer images averaged, delaying the start of the protocol resulted in more accurate correction because of the influence of unrepresentative positions at early fractions. The number of corrections made on patients with small (< 2 mm) systematic errors was minimized for tolerance values of 2 mm and n > or = 5 images averaged. The optimal off-line setup correction protocol would be to shift the patient by the mean displacement of the first 5 portal images of a radical course of radiation therapy. A small tolerance level should be utilized with 2 mm giving good accuracy with minimal unnecessary shifts.

Retrospective analysis of prostate cancer patients with implanted gold markers using off-line and adaptive therapy protocols

To determine the efficacy of applying adaptive and off-line setup correction models to bony anatomy and gold fiducial markers implanted in the prostate, relative to daily alignment to skin tattoos and daily on-line corrections of the implanted gold markers. Ten prostate cancer patients with implanted gold fiducial markers were treated using a daily on-line setup correction protocol. The patients' positions were aligned to skin tattoos and two orthogonal diagnostic digital radiographs were obtained before treatment each day. These radiographs were compared with digitally reconstructed radiographs to obtain the translational setup errors of the bony anatomy and gold markers. The adaptive, no-action-level and shrinking-action-level off-line protocols were retrospectively applied to the bony anatomy to determine the change in the setup errors of the gold markers. The protocols were also applied to the gold markers directly to determine the residual setup errors. The percentage of remaining fractions that the gold markers fell within the adaptive margins constructed with 1.5sigma' (estimated random variation) after 5, 10, and 15 measurement fractions was 74%, 88%, and 93% for the prone patients and 55%, 77%, and 93% for the supine patients, respectively. Using 2sigma', the percentage after 5, 10, and 15 measurements was 85%, 95%, and 97% for the prone patients and 68%, 87%, and 99% for the supine patients, respectively. The average initial three-dimensional (3D) setup error of the gold markers was 0.92 cm for the prone patients and 0.70 cm for the supine patients. Application of the no-action-level protocol to bony anatomy with N(m) = 3 days resulted in significant benefit to 4 of 10 patients, but 3 were significantly worse. The residual average 3D setup error of the gold markers was 1.14 cm and 0.51 cm for the prone and supine patients, respectively. When applied directly to the gold markers with N(m) = 3 days, 5 patients benefited and 3 were significantly worse. The residual 3D error of the gold markers was 1.14 cm and 0.76 cm for the prone and supine patients, respectively. Application of the shrinking-action-level protocol to bony anatomy with an initial action level of 1.0 cm and N(max) = 5 days decreased the residual systematic offset of the gold markers in 2 of 10 patients. The residual average 3D setup error of the gold markers was 1.2 cm and 1.0 cm for the prone and supine patients, respectively. When applied directly to the gold markers with N(max) = 5 days, the residual systematic offset of the gold markers decreased in 6 of 10 patients (0.84 cm and 0.67 cm for the prone and supine patients, respectively). In general, between 3 and 5 of the 10 patients showed significant decreases in setup errors with the application of these off-line protocols, and the remaining patients showed no significant improvement or showed significantly larger setup errors, as determined by the residual error of the gold markers. Changes in a prostate cancer patient's systematic and random setup characteristics during the course of therapy often violate the gaussian assumptions of adaptive and off-line correction models. Thus, off-line setup correction procedures, especially those directed at prostate localization using markers, will result in limited benefit to a minority of patients. The relative benefit of on-line localization is still potentially significant if the intrafraction motion is relatively small.