Smaller Safety Margins Research Articles

Definitive, intensity modulated tomotherapy with a simultaneous integrated boost for prostate cancer patients - Long term data on toxicity and biochemical control.

To report long-term data regarding biochemical control and late toxicity of simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) with tomotherapy in patients with localized prostate cancer. Dose escalation improves cancer control after curative intended radiation therapy (RT) to patients with localized prostate cancer, without increasing toxicity, if IMRT is used. In this retrospective analysis, we evaluated long-term toxicity and biochemical control of the first 40 patients with intermediate risk prostate cancer receiving SIB-IMRT. Primary target volume (PTV) 1 including the prostate and proximal third of the seminal vesicles with safety margins was treated with 70Gy in 35 fractions. PTV 2 containing the prostate with smaller safety margins was treated as SIB to a total dose of 76Gy with 2.17Gy per fraction. Toxicity was evaluated using an adapted CTCAE-Score (Version 3). Median follow-up of living patients was 66 (20-78) months. No late genitourinary toxicity higher than grade 2 has been reported. Grade 2 genitourinary toxicity rates decreased from 58% at the end of the treatment to 10% at 60 months. Late gastrointestinal (GI) toxicity was also moderate, though the prescribed PTV Dose of 76Gy was accepted at the anterior rectal wall. 74% of patients reported any GI toxicity during follow up and no toxicity rates higher than grade 2 were observed. Grade 2 side effects were reported by 13% of the patients at 60 months. 5-year freedom from biochemical failure was 95% at our last follow up. SIB-IMRT using daily MV-CT guidance showed excellent long-term biochemical control and low toxicity rates.

Electrochemotherapy in the treatment of neoplasms in dogs and cats

Abstract: Electrochemotherapy (ECT) is a technique that combines chemotherapy with local application of specific electric pulses with the aim of increasing the permeability of the plasma membrane in a reversible way, improving the influx of chemotherapeutic drugs into the cytoplasm and potentiating their cytotoxic effects. This technique has broadened the range of possible treatments for oncological patients, either on its own or as adjuvant to surgical procedures. It is especially useful in tumors located in regions with only a small surgical safety margin, such as the limb extremities, skull, oral cavity, neck and perianal region, among others. ECT makes it feasible to perform procedures more conservatively, or even to perform otherwise infeasible procedures, by expanding the margins without removing healthy tissues. The objective of this paper is to provide a brief bibliographic review of the principles, applications and future possibilities of electrochemotherapy, helping to disseminate pertinent information about this relatively new technique for the treatment of cancer.

Determination of limiting values of 1H spin-spin relaxation time to assess lifetime of thermally aged acrylonitrile butadiene rubber

We propose a method to determine the limiting value of 1H spin–spin relaxation time (T2) for assessing the lifetime of thermally aged acrylonitrile butadiene rubber (NBR) parts. So far, it has been difficult to determine the limiting values of T2 without performing other experiments such as mechanical property measurements and air tightness tests. We exposed two types of NBR diaphragm sheets to air at 100 °C for up to 7540 h and 6000 h, respectively. After that, we tested their air-tightness and we measured T2 of the virgin and aged diaphragms. To evaluate the temperature dependence of T2, T2 measurements were performed at 20, 40, and 60 °C. Additionally, we observed the 13C Nuclear Magnetic Resonance (NMR) spectra, toluene swelling ratio, acetone soluble fraction, and glass transition temperature for only one type of the diaphragm sheets. The diaphragm aged for 7540 h had lost sealability, and all the results indicated that this was caused by the degradation of NBR. The 13C NMR spectra clearly revealed that the degradation of NBR proceeded in three stages: self-cross-linking reactions in the initial stage, concurrent reactions of cross-linking and molecular chain scission in the second stage, and an increased number of reactions of cross-linking and molecular chain scission in the final stage. The results of the T2 measurements showed that T2 is useful not only to evaluate the complicated degradation behavior quantitatively, but also to determine the different limiting values of T2 itself corresponding to large and small safety margins. Finally, we demonstrated that the temperature dependence of T2 is an effective parameter for quantitatively predicting the ultimate lifetime at each aging temperature with no safety margin for various thermally aged NBR rubber sheets.

Cavity volume changes after surgery of a brain metastasis—consequences for stereotactic radiation therapy

For alarge or symptomatic brain metastasis, resection and adjuvant radiotherapy are recommended. Hypofractionated stereotactic radiotherapy (HFSRT) is increasingly applied in patients with alimited number of lesions. Exact target volume definition is critical given the small safety margins. Whilst technical advances have minimized inaccuracy due to patient positioning and radiation targeting, little is known about changes in target volume. This study sought to evaluate potential changes in the resection cavity of abrain metastasis. In all, 57patients treated with HFSRT after surgical resection of one brain metastasis between 2008 and 2015 in our institution were included in this study. Gross tumor volume (GTV) of the initial metastasis and the volume of the resection cavity in the post-operative, planning, and follow-up MRIs were measured and compared. The mean cavity size decreased after surgery with the greatest change of -23.4% (±41.5%) occurring between post-operative MRI and planning MRI (p < 0.01). During this time period, the cavity volume decreased, remained stable, and increased in 79.1, 3.5, and 17.4%, respectively. Afurther decrease of -20.7% (±58.1%) was perceived between planning MRI and first follow-up (p < 0.01). No significant difference in pattern of change could be observed depending on the volume of initial GTV, size of the post-operative resection cavity, initial or post-resection FLAIR (fluid-attenuated inversion recovery) hyper-intensity, postsurgical ischemia, or primary tumor. The resection cavities of patients with post-operative ischemia were significantly larger than resection cavities of patients without ischemia. The resection cavity seems to be very dynamic after surgery. Hence, it remains necessary to use very recent scans for treatment planning.

PO348 Designing and Evaluating the Efficacy of Mobile Cardiac Arrhythmia Simulator Application on Critical Care Nurses’ Knowledge and Satisfaction

To determine intrafraction prostate motion during volumetric modulated arc therapy (VMAT) using transperineal ultrasound (US) real-time tracking.770 US monitoring sessions in 38 prostate cancer patients' VMAT treatment series were retrospectively evaluated. Intrafraction motion assessment of the prostate was based on continuous position monitoring with a 4-dimensional US system along the 3 directions: left-right (LR), anterior-posterior (AP), and inferior-superior (SI). The overall mean values and standard deviations (SD) along with random and systematic errors were calculated.The mean duration of each monitoring session was 254 s. The mean (μ), the systematic error (Σ), and the random error (σ) of intrafraction prostate displacement were μ = (0.01, −0.08, 0.15) mm, Σ = (0.30, 0.34, 0.23) mm, and σ = (0.59, 0.73, 0.64) mm in the LR, AP and SI directions, respectively. The percentage of treatments for which prostate displacement was ≤2 mm was 97.01%, 92.24%, and 95.77% in the LR, AP, and SI directions, respectively. At 60 s, a vector length of prostate displacement >2 mm was present in 0.67% of the data. The percentage increased to 2.42%, 6.14%, and 9.35% at 120 s, 180 s, and 240 s, respectively.The magnitudes of intrafraction prostate motion along the SI and AP directions were comparable. On average, the smallest motion was in the LR direction and the largest in AP direction. Most of the prostate displacements were within a few millimeters. However, with increasing treatment time (eg, during hypofractionation), larger 3-dimensional prostate displacements up to 18.30 mm could be observed. Shortening treatment time can reduce the impact of intrafraction motion and potentially allows smaller safety margins.

Probabilistic serviceability-performance assessment of tall mass-timber buildings subjected to stochastic wind loads: Part I - structural design and wind tunnel testing

Tall mass-timber buildings utilize engineered wood panels to form their main gravity and lateral load resisting systems, which makes them lighter and very flexible. As a result, frequent exposure to excessive wind-induced vibrations can cause occupant discomfort and unserviceability due to horizontal floor acceleration and excessive deflection. Therefore, the objective of this and the companion paper is to assess the serviceability performance of tall mass-timber buildings probabilistically. For this purpose, the Alan G. Davenport Wind Loading Chain is adapted as a probabilistic Performance-Based Wind Engineering framework. The framework is applied to quantify the serviceability performance of a 102-m tall mass-timber building. In this paper, a complete tall-mass timber building structural design process is outlined. Wind loads are obtained from aerodynamic wind tunnel tests conducted at the Boundary Layer Wind Tunnel Laboratory at Western University. The design process involves preliminary strength design using the provisions of building codes, design revisions using wind load from wind tunnel tests, and serviceability checks. The structural design of the case study tall mass-timber building considers the axial compression, in-plane-shear, and in-plane and out-of-plane bending moment demands, along with their interactions due to gravity and wind loads. Dynamic analysis is carried out to assess the drift performance of the case study mass-timber building. The results show that the building satisfies the drift requirements prescribed by the building codes with a small safety margin. For the designed tall mass-timber building, an in-depth probabilistic serviceability-performance assessment and vulnerability estimations are presented in the companion paper.

Learning from every patient treated

Modern precision radiotherapy allows small safety margins and dose escalation. Therefore, biological factors become much more important such as CTV delineation and thresholds for organ at risk tolerance. Our aim is to develop image based data mining for exploring voxel-based dose–response relationships in very large patient cohorts. Large numbers of planning CTs are deformably registered to a reference CT. Registration uncertainties are quantified using organ-at-risk contours, dose distributions are smoothed according to these uncertainties and mapped onto the reference. Next outcome measures are correlated voxel-by-voxel with the dose distributions. The resulting correlation maps are tested for significance using a test statistic, e.g. maximum t-value, using randomization to test for significance. We have applied this methodology in several tumour sites and a great strength of this technique is that it allows discovery of sensitive sub-structures of organs. For example, in lung cancer we demonstrated a relationship of dose to the base of the heart with early mortality (1100 patients); while in head and neck cancer, masseter dose correlated most with post treatment trismus. In prostate cancer, obturator dose relates to PSA control. To understand the results, it is important to study inherent correlations in voxel-wise dose distributions that are related to planning techniques that are often ignored in dose-volume based analyses. We conclude that voxel based dose response relationships can be discovered efficiently using deformable registration and novel statistical techniques and that these complement traditional dose–volume analyses, and are suitable for very large patient cohorts.

Determination of Intrafraction Prostate Motion During External Beam Radiation Therapy With a Transperineal 4-Dimensional Ultrasound Real-Time Tracking System

To determine intrafraction prostate motion during volumetric modulated arc therapy (VMAT) using transperineal ultrasound (US) real-time tracking. 770 US monitoring sessions in 38 prostate cancer patients' VMAT treatment series were retrospectively evaluated. Intrafraction motion assessment of the prostate was based on continuous position monitoring with a 4-dimensional US system along the 3 directions: left-right (LR), anterior-posterior (AP), and inferior-superior (SI). The overall mean values and standard deviations (SD) along with random and systematic errors were calculated. The mean duration of each monitoring session was 254s. The mean (μ), the systematic error (Σ), and the random error (σ) of intrafraction prostate displacement were μ = (0.01, -0.08, 0.15) mm, Σ = (0.30, 0.34, 0.23) mm, and σ = (0.59, 0.73, 0.64) mm in the LR, AP and SI directions, respectively. The percentage of treatments for which prostate displacement was ≤2mm was 97.01%, 92.24%, and 95.77% in the LR, AP, and SI directions, respectively. At 60s, a vector length of prostate displacement >2mm was present in 0.67% of the data. The percentage increased to 2.42%, 6.14%, and 9.35% at 120s, 180s, and 240s, respectively. The magnitudes of intrafraction prostate motion along the SI and AP directions were comparable. On average, the smallest motion was in the LR direction and the largest in AP direction. Most of the prostate displacements were within a few millimeters. However, with increasing treatment time (eg, during hypofractionation), larger 3-dimensional prostate displacements up to 18.30mm could be observed. Shortening treatment time can reduce the impact of intrafraction motion and potentially allows smaller safety margins.

Thermoregulatory behavior and high thermal preference buffer impact of climate change in a Namib Desert lizard

AbstractKnowledge of the thermal ecology of a species can improve model predictions for temperature‐induced population collapse, which in light of climate change is increasingly important for species with limited distributions. Here, we use a multi‐faceted approach to quantify and integrate the thermal ecology, properties of the thermal habitat, and past and present distribution of the diurnal, xeric‐adapted, and active‐foraging Namibian lizard Pedioplanis husabensis (Sauria: Lacertidae) to model its local extinction risk under future climate change scenarios. We asked whether climatic conditions in various regions of its range are already so extreme that local extirpations of P. husabensis have already occurred, or whether this micro‐endemic species is adapted to these extreme conditions and uses behavior to mitigate the environmental challenges. To address this, we collected thermoregulation and climate data at a micro‐scale level and combined it with micro‐ and macroclimate data across the species’ range to model extinction risk. We found that P. husabensis inhabits a thermally harsh environment, but also has high thermal preference. In cooler parts of its range, individuals are capable of leaving thermally favorable conditions—based on the species’ thermal preference—unused during the day, probably to maintain low metabolic rates. Furthermore, during the summer, we observed that individuals regulate at body temperatures below the species’ high thermal preference to avoid body temperatures approaching the critical thermal maximum. We find that populations of this species are currently persisting even at the hottest localities within the species’ geographic distribution. We found no evidence of range shifts since the 1960s despite a documented increase in air temperatures. Nevertheless, P. husabensis only has a small safety margin between the upper limit of its thermal preference and the critical thermal maximum and might undergo range reductions in the near future under even the most moderate climate change scenarios.

A Novel Method for the Delivery of 3-Dimensional High-Dose Spatially Fractionated Radiation Therapy With Pencil Beam Scanning Proton Therapy: Maximizing the Benefit of the Bragg Peak

High dose spatially fractionated (GRID) radiotherapy has been utilized sparingly in clinical practice by means of traditional photon techniques. However, this approach has shown great potential to allow for safe dose-escalation in large tumors by mimicking brachytherapy distributions on an external beam platform. While both scattered and scanned particle beams have been proposed for this application, all previously reported models utilize spatially fractionated spread out Bragg peaks (SOBPs), that, while providing less than ideal valleys and peaks of GRID therapy, substantially increase entrance dose and fail to take full advantage of the enhanced radiobiologic effect (RBE) at end of range. We hypothesized that pencil beam scanning proton therapy (PBS-PT) based GRID plans could be developed utilizing only pristine Bragg peaks (without SOBPs), addressing each of these issues. Five patients with tumors greater than 10 cm in greatest dimension and in different anatomical sites (head/neck, lung, abdomen, pelvis, and extremity) were identified retrospectively. Gross tumor volume was delineated and contracted by a small safety margin to ensure that all Bragg peaks would fall within tumoral tissue. A trained physicist delineated a 3-dimensional lattice of 3 mm spherical targets, spaced center-to-center 3 cm apart, each intended to be treated by an individual “spot.” Two beam angles were utilized for each plan, and the target lattice was rotated in 3 dimensions to prevent spot stacking. Inverse optimization with manual spot map modifications were employed. Plan peak-to-valley ratios were optimized to be consistent with those achieved by photon-based GRID in our clinic. All plans achieved consistent maximum dose (Dmax) peaks approximating 15 Gy(RBE) with a confluent valley dose across targeted tumor of ∼1-2 Gy(RBE). The depth of valleys was able to be modulated based on target lattice spacing. No SOBPs were utilized in planning, instead, each spot entrance path was only utilized once, though laterally penumbra was allowed to overlap in the valleys. In even superficial targets, maximum skin dose was reduced to less than 50% Dmax to small islands of surface tissue, as is customary with GRID. All Bragg peaks terminated within gross tumor offering the potential for enhanced tumoral RBE with maximal sparing of tissues beyond the target. Plans incorporated between 11 and 28 energy layers and from 42 to 157 total spots. PBS-PT based GRID therapy can be achieved solely utilizing pristine Bragg peaks without need for SOBP or spot stacking. This technique offers the promise of dose escalation, maximal skin, and organ at risk sparing, and enhanced tumoral RBE. Efforts to develop algorithmic automation and inverse optimization of this methodology are underway.

The effect of anisotropy on the optimization of additively manufactured lattice structures

The build orientation is one the most influential factors on material properties in additively manufactured parts. Advanced applications, such as lattice structures optimized for lightweight, often rely on small safety margins and are, hence, particularly affected, but research has not gone far beyond the pure empirical characterization. The focus of this paper is to investigate in detail the influence of anisotropy induced through fabrication on the mechanical performance and build orientation of whole structures when subject to optimization. First, a material property model for both compression and tension states is formulated. Then, the Generalized Optimality Criteria method is extended for fixed topology lattice structures with respect to constraints in displacement, stress, and Euler buckling. The two latter are formulated as local constraints that are handled in combination with Fully-Stressed Design recursion. The results reveal significant safety threads likely leading to premature failure when using properties from one-directional tests, as is so far the case, rather than the full anisotropy model developed herein. If used inversely, the algorithm yields the optimal orientation of a structure on the build platform, allowing further weight reduction while maintaining the mechanical properties.

Factors contributing to commercial vehicle rear-end conflicts in China: A study using on-board event data recorders

Introduction: In the last 30years, China has undergone a dramatic increase in vehicle ownership and a resulting escalation in the number of road crashes. Although crash figures are decreasing today, they remain high; it is therefore important to investigate crash causation mechanisms to further improve road safety in China. Method: To shed more light on the topic, naturalistic driving data was collected in Shanghai as part of the evaluation of a behavior-based safety service. The data collection included instrumenting 47 vehicles belonging to a commercial fleet with data acquisition systems. From the overall sample, 91 rear-end crash or near-crash (CNC) events, triggered by 24 drivers, were used in the analysis. The CNC were annotated by three researchers, through an expert assessment methodology based on videos and kinematic variables. Results: The results show that the main factor behind the rear-end CNC was the adoption of very small safety margins. In contrast to results from previous studies in the US, the following vehicles' drivers typically had their eyes on the road and reacted quickly in response to the evolving conflict in most events. When delayed reactions occurred, they were mainly due to driving-related visual scanning mismatches (e.g., mirror checks) rather than visual distraction. Finally, the study identified four main conflict scenarios that represent the typical development of rear-end conflicts in this data. Conclusions: The findings of this study have several practical applications, such as informing the specifications of in-vehicle safety measures and automated driving and providing input into the design of coaching/training procedures to improve the driving habits of drivers.

Retention of stored water enables tropical tree saplings to survive extreme drought conditions.

Trees generally maintain a small safety margin between the stem water potential (Ψstem) reached during seasonal droughts and the Ψstem associated with their mortality. This pattern may indicate that species face similar mortality risk during extreme droughts. However, if tree species vary in their ability to regulate Ψstem, then safety margins would poorly predict drought mortality. To explore variation among species in Ψstem regulation, I subjected potted saplings of six tropical tree species to extreme drought and compared their responses with well-watered plants and pretreatment reference plants. In the drought treatment, soil water potential reached <-10 MPa, yet three species, Bursera simaruba (L.) Sarg., Cavanillesia platanifolia (Bonpl.) Kunth and Cedrela odorata L. had 100% survival and maintained Ψstem near -1 MPa (i.e., desiccation-avoiding species). Three other species, Cojoba rufescens (Benth.) Britton and Rose, Genipa americana L. and Hymenaea courbaril L. had 50%, 0% and 25% survival, respectively, and survivors had Ψstem <-6 MPa (i.e., desiccation-susceptible species). The desiccation-avoiding species had lower relative water content (RWC) in all organs and tissues (root, stem, bark and xylem) in the drought treatment than in the reference plants (means 72.0-90.4% vs 86.9-97.9%), but the survivors of the desiccation-susceptible C. rufescens had much lower RWC in the drought treatment (44.5-72.1%). Among the reference plants, the desiccation-avoiding species had lower tissue density, leaf-mass fraction and lateral-root surface area (LRA) than the desiccation-susceptible species. Additionally, C. platanifolia and C. odorata had reduced LRA in the drought treatment, which may slow water loss into dry soil. Together, these results suggest that the ability to regulate Ψstem during extreme drought is associated with functional traits that favor retention of stored water and that safety margins during seasonal drought poorly predict survival during extreme drought.

Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas).

Diclofenac is one of the most widely prescribed nonsteroidal anti-inflammatory drugs worldwide. It is frequently detected in surface waters; however, whether this pharmaceutical poses a risk to aquatic organisms is debated. Here we quantified the uptake of diclofenac by the fathead minnow (Pimephales promelas) following aqueous exposure (0.2-25.0 μg L-1) for 21 days, and evaluated the tissue and biomolecular responses in the kidney. Diclofenac accumulated in a concentration- and time-dependent manner in the plasma of exposed fish. The highest plasma concentration observed (for fish exposed to 25 μg L-1 diclofenac) was within the therapeutic range for humans. There was a strong positive correlation between exposure concentration and the number of developing nephrons observed in the posterior kidney. Diclofenac was not found to modulate the expression of genes in the kidney associated with its primary mode of action in mammals (prostaglandin-endoperoxide synthases) but modulated genes associated with kidney repair and regeneration. There were no significant adverse effects following 21 days exposure to concentrations typical of surface waters. The combination of diclofenac's uptake potential, effects on kidney nephrons and relatively small safety margin for some surface waters may warrant a longer term chronic health effects analysis for diclofenac in fish.

Serviceability of Fabric-Formed Concrete Structures

Fabric form-work is a newly developed technique to cast concrete structures with a great advantage of saving concrete material of up to 40%. This technique is particularly associated with optimized concrete structures that usually have smaller cross-section dimensions than equivalent prismatic members. However, this can make the structural system produced from these members prone to smaller serviceability safety margins. Therefore, it is very important to understand serviceability issue of non-prismatic concrete structures. In this paper, an analytical computer-based model to optimize concrete beams and to predict load-deflection behaviour of both prismatic and non-prismatic concrete beams is presented. The model was developed based on the method of sectional analysis and integration of curvatures. Results from the analytical model were compared to load-deflection behaviour of a number of beams with different geometric and material properties from other researchers. The results of the comparison show that, the analytical program can accurately predict load-deflection response of concrete beams with medium reinforcement ratios. However, it over-estimates deflection values for lightly reinforced specimens. Finally, the analytical program acceptably predicted load-deflection behaviour of on-prismatic concrete beams.

Convergence of leaf‐out towards minimum risk of freezing damage in temperate trees

Summary Within the same forest stand, temperate deciduous trees generally exhibit a distinct pattern in leaf‐out timing, with some species flushing earlier than other species. This study aimed to explain the timing of leaf‐out of various temperate tree species in relation to the risk of freezing damage to leaves. We combined long‐term series of leaf‐out date (14–32 years) of five temperate tree species located in both low and high elevations in Switzerland, daily minimum temperatures recorded at the same sites and species‐specific freezing resistance (LT50) of emerging leaves. We calculated temperature safety margins (the temperature difference between absolute minimum temperature during leaf‐out and species‐specific LT50 values), and date safety margins (time lag between the last day when temperature falls below species‐specific LT50 values and the date of leaf‐out). Leaf‐out occurred when the probability to encounter freezing damage approaches zero, irrespective of climatic conditions (low vs. high elevation) and species (early‐ and late‐flushing species). In other words, trees leaf out precisely at the beginning of the probabilistically safe period. Interestingly, the temperature safety margins did not differ significantly between low and high elevation. Yet, the date safety margin was smaller at high elevation, presumably due to a faster increase in temperature during the leaf‐out period at high elevation. When species‐specific freezing resistance is taken into account, the time of leaf‐out converges among species towards a marginal risk of freezing damage. Thus, leaf‐out time has likely evolved in a way that the risk of freezing damage is minimized over a large spectrum of climatic conditions. Species with a small safety margin against freezing temperature, like Fagus sylvatica, appear to employ photoperiod co‐control of spring phenology, whereas species with a large safety margin depend largely on temperature for the right timing of leaf‐out. Our results offer a new avenue to explain the differences in leaf‐out timing among co‐occurring tree species. They further suggest that in a warming climate, tree species can expand their distribution range to the extent their phenology matches the stochasticity of freezing temperatures in spring.

Prostate cancer treated with image-guided helical TomoTherapy® and image-guided LINAC-IMRT

We compared different image-guidance (IG) strategies for prostate cancer with high-precision IG intensity-modulated radiation therapy (IMRT) using TomoTherapy® (Accuray Inc., Madison, WI, USA) and linear accelerator (LINAC)-IMRT and their impact on planning target volume (PTV) margin reduction. Follow-up data showed reduced bladder toxicity in TomoTherapy patients compared to LINAC-IMRT. The purpose of this study was to quantify whether the treatment delivery technique and decreased margins affect reductions in bladder toxicity. Setup corrections from 30patients treated with helical TomoTherapy and 30treated with a LINAC were analyzed. These data were used to simulate three IG protocols based on setup error correction and a limited number of imaging sessions. For all patients, gastrointestinal (GI) and genitourinary (GU) toxicity was documented and correlated with the treatment delivery technique. For fiducial marker (FM)-based RT, a margin reduction of up to3.1, 3.0, and 4.8mm in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively, could be achieved with calculation of a setup correction from the first three fractions and IG every second day. Although the bladder volume was treated with mean doses of 35Gy in the TomoTherapy group vs. 22Gy in the LINAC group, we observed less GU toxicity after TomoTherapy. Intraprostate FMs allow for small safety margins, help decrease imaging frequency after setup correction, and minimize the dose to bladder and rectum, resulting in lower GU toxicity. In addition, IMRT delivered with TomoTherapy helps to avoid hotspots in the bladder neck, a critical anatomic structure associated with post-RT urinary toxicity.

Gap Acceptance Behavior of Mobile Phone–Distracted Drivers at Roundabouts

The use of mobile phones while driving is increasing at an alarming rate despite the associated crash risks. A significant safety concern is that driving while distracted by a mobile phone is more prevalent among young drivers, a less experienced driving cohort with elevated crash risk. The objective of this study was to examine the gap acceptance behavior of distracted young drivers at roundabouts. The Center for Accident Research and Road Safety–Queensland Advanced Driving Simulator was used to test participants on a simulated gap acceptance scenario at roundabouts. Conflicting traffic approaching from the right of a four-legged roundabout was programmed to show a series of vehicles with the gaps between them proportionately increased from 2 s to 6 s. Thirty-two licensed young drivers drove the simulator under three phone conditions: baseline (no phone conversation), a hands-free phone conversation, and a handheld phone conversation. Results show that distracted drivers started responding to the gap acceptance scenario when they were closer to the roundabout and they approached the roundabout at slower speeds. These drivers also decelerated at faster rates to reduce their speeds before gap acceptance compared with nondistracted drivers. Although accepted gap sizes were not significantly different across phone conditions, differences in the safety margin at various gap sizes—measured by postencroachment time (PET) between the driven vehicle and the conflicting vehicle—were statistically significant across phone conditions. PETs for distracted drivers were smaller across different gap sizes and suggest that a smaller safety margin was accepted by distracted drivers compared with nondistracted drivers.

Quantifying drivers’ comfort-zone and dread-zone boundaries in left turn across path/opposite direction (LTAP/OD) scenarios

The aim of this study is to quantify drivers’ comfort- and dread-zone boundaries in left-turn-across-path/opposite-direction (LTAP/OD) scenarios. These scenarios account for a large fraction of traffic fatalities world-wide. The comfort zone is a dynamic spatiotemporal envelope surrounding the vehicle, within which drivers feel comfortable and safe. The dread zone, a novel concept, describes a zone with a smaller safety margin that drivers will not voluntarily enter, but can push themselves into when conditions provide additional motivation (e.g., when hurried). Quantifying comfort- and dread-zone boundaries in the context of turning left before or after an oncoming vehicle has the potential to inform and improve both the design and driver acceptance of advanced driver assistance systems (ADAS) and autonomous vehicles.Using a within-subject design, a test-track experiment was conducted with drivers turning an instrumented vehicle left across the path of an oncoming vehicle. The oncoming vehicle was a self-propelled full-sized computer-controlled balloon vehicle going straight at a constant speed (50km/h). The driver assumed full control of the instrumented vehicle approximately 20m before the intersection and had to make the decision to turn left before or after the oncoming balloon vehicle. There were two experimental conditions, comfortable driving and hurried driving. Measures for each turn included post-encroachment time (PET), lateral acceleration, and self-reports of comfort and risk. Drivers consistently accepted shorter time gaps and higher lateral accelerations when hurried. We interpret these findings to suggest that drivers invoke two dynamic, contextually-defined safety margins. The first is the comfort-zone boundary, a limit which drivers do not voluntarily cross without extra motives. The second is the dread-zone boundary, a more distant limit which drivers do not voluntarily cross even with extra motives. Grouping the responses (high/low) to the driver behavior questionnaire (DBQ) improved the ability to predict the dread-zone boundary PET given the comfort-zone boundary PET.

Coordination of xylem hydraulics and stomatal regulation in keeping the integrity of xylem water transport in shoots of two compound-leaved tree species

Hydraulic segmentation between proximal and distal organs has been hypothesized to be an important protective mechanism for plants to minimize the detrimental effects of drought-induced hydraulic failure. Uncertainties still exist regarding the degree of segmentation and the role of stomatal regulation in keeping hydraulic integrity of organs at different hierarchies. In the present study, we measured hydraulic conductivity and vulnerability in stems, compound leaf petioles and leaflet laminas of Fraxinus mandshurica Rupr. and Juglans mandshurica Maxim. growing in Changbai Mountain of Northeast China to identify the main locality where hydraulic segmentation occurs along the shoot water transport pathway. Stomatal conductance in response to leaf water potential change was also measured to investigate the role of stomatal regulation in avoiding extensive transpiration-induced embolism. No major contrasts were found between stems and compound leaf petioles in either hydraulic conductivity or vulnerability to drought-induced embolism, whereas a large difference in hydraulic vulnerability exists between compound leaf petioles and leaflet laminas. Furthermore, in contrast to the relatively large safety margins in stems (4.13 and 2.04 MPa) and compound leaf petioles (1.33 and 1.93 MPa), leaflet lamina hydraulic systems have substantially smaller or even negative safety margins (-0.17 and 0.47 MPa) in F. mandshurica and J. mandshurica. Under unstressed water conditions, gas exchange may be better optimized by allowing leaflet vascular system function with small safety margins. In the meantime, hydraulic safety of compound leaf petioles and stems are guaranteed by their large safety margins. In facing severe drought stress, larger safety margins in stems than in compound leaf petioles would allow plants to minimize the risk of catastrophic embolism in stems by sacrificing the whole compound leaves. A strong coordination between hydraulic and stomatal regulation appears to play a critical role in balancing the competing efficiency and safety requirements for xylem water transport and use in plants.