Enhancing Safety in AI-Driven Cone Beam CT-based Online Adaptive Radiation Therapy: Development and Implementation of an Interdisciplinary Workflow.

Purpose: The emerging online adaptive radiation therapy (OART) treatment strategy based on cone beam computed tomography allows for real-time replanning according to a patient's current anatomy. However, implementing this procedure requires a new approach across the patient's care path and monitoring of the "black box" adaptation process. This study identifies high-risk failure modes (FMs) associated with AI-driven OART and proposes an interdisciplinary workflow to mitigate potential medical errors from highly automated processes, enhance treatment efficiency, and reduce the burden on clinicians. Methods and Materials: An interdisciplinary working group was formed to identify safety concerns in each process step using failure mode and effects analysis (FMEA). Based on the FMEA results, the team designed standardized procedures and safety checklists to prevent errors and ensure successful task completion. The Risk Priority Numbers (RPNs) for the top twenty FMs were calculated before and after implementing the proposed workflow to evaluate its effectiveness. Three hundred seventy-four adaptive sessions across 5 treatment sites were performed, and each session was evaluated for treatment safety and FMEA assessment. Results: The OART workflow has 4 components, each with 4, 8, 13, and 4 sequentially executed tasks and safety checklists. Site-specific template preparation, which includes disease-specific physician directives and Intelligent Optimization Engine template testing, is one of the new procedures introduced. The interdisciplinary workflow significantly reduced the RPNs of the high-risk FMs, with an average decrease of 110 (maximum reduction of 305.5 and minimum reduction of 27.4). Conclusions: This study underscores the importance of addressing high-risk FMs associated with AI-driven OART and emphasizes the significance of safety measures in its implementation. By proposing a structured interdisciplinary workflow and integrated checklists, the study provides valuable insights into ensuring the safe and efficient delivery of OART while facilitating its effective integration into clinical practice.

Scorecards: Quantifying Dosimetric Plan Quality in Pancreatic Ductal Adenocarcinoma Stereotactic Body Radiation Therapy.

Purpose: A scoring mechanism called the scorecard that objectively quantifies the dosimetric plan quality of pancreas stereotactic body radiation therapy treatment plans is introduced. Methods and Materials: A retrospective analysis of patients with pancreatic ductal adenocarcinoma receiving stereotactic body radiation therapy at our institution between November 2019 and November 2020 was performed. Ten patients were identified. All patients were treated to 36 Gy in 5 fractions, and organs at risk (OARs) were constrained based on Alliance A021501. The scorecard awarded points for OAR doses lower than those cited in Alliance A021501. A team of 3 treatment planners and 2 radiation oncologists, including a physician resident without plan optimization experience, discussed the relative importance of the goals of the treatment plan and added additional metrics for OARs and plan quality indexes to create a more rigorous scoring mechanism. The scorecard for this study consisted of 42 metrics, each with a unique piecewise linear scoring function which is summed to calculate the total score (maximum possible score of 365). The scorecard-guided plan, the planning and optimization for which were done exclusively by the physician resident with no prior plan optimization experience, was compared with the clinical plan, the planning and optimization for which were done by expert dosimetrists, using the Sign test. Results: Scorecard-guided plans had, on average, higher total scores than those clinically delivered for each patient, averaging 280.1 for plans clinically delivered and 311.7 for plans made using the scorecard (P = .003). Additionally, for most metrics, the average score of each metric across all 10 patients was higher for scorecard-guided plans than for clinically delivered plans. The scorecard guided the planner toward higher coverage, conformality, and OAR sparing. Conclusions: A scorecard tool can help clarify the goals of a treatment plan and provide an objective method for comparing the results of different plans. Our study suggests that a completely novice treatment planner can use a scorecard to create treatment plans with enhanced coverage, conformality, and improved OAR sparing, which may have significant effects on both tumor control and toxicity. These tools, including the scorecard used in this study, have been made freely available.

Impact of Adapted Radiotherapy Schedules on Bowel Sparing in Node-Positive Cervical Cancer.

PURPOSE: Definitive radiation therapy (RT) for locally advanced node-positive cervical cancer confers significant toxicity to pelvic organs including the small bowel. Gross nodal disease exhibits significant shrinkage during RT, and yet conventional RT does not account for this change. We evaluated the reduction in absorbed bowel dose using various adaptive RT schedules. METHODS AND MATERIALS: We obtained 130 evaluable scans (computed tomography simulation and 25 cone beam computed tomography scans per patient) of 5 patients who had received definitive external beam RT for lymph node positive cervical cancer daily over 5 weeks. Using a single universal volumetric modulated arc therapy plan with predefined optimization priorities, we created adapted RT plans in 4 schedules: Daily, Weekly, Twice, and NoAdapt (mimicking conventional nonadapted RT). The in silico (computer modeled) patients were treated to 45 Gy to primary cervical disease with a simultaneous integrated boost to 55 Gy to involved lymph nodes. We evaluated dose metrics including D2cc, D15cc, and V45 to determine the impact of adapted RT schedules on bowel sparing. Statistical tests included the Student t test, analysis of variance, and the Spearman rank correlation. RESULTS: The quantity of reduced bowel dose was significantly associated with the chosen planning schedule in all evaluated metrics and was proportional to the frequency of adaptive RT with significant moderate-to-strong monotonicity. Both D2cc and D15cc were reduced an average of 2.7 Gy using daily replanning compared with a nonadapted approach. A minimally adapted strategy of only 2 replans also confers a significant dosimetric benefit over a nonadapted approach. Reduced standard deviations of D2cc and V45 bowel doses over the treatment courses were significantly associated with the choice of planning schedule with strong monotonicity. CONCLUSIONS: All adaptive RT schedules evaluated confer significant dosimetric advantages in bowel sparing over a conventional nonadapted technique, with greater sparing seen with more frequent replanning schedules. These findings warrant future trials of adaptive RT for pelvic malignancies.

Effects of Flywheel Training With Eccentric Overload on Standing Balance, Mobility, Physical Function, Muscle Thickness, and Muscle Quality in Older Adults.

ABSTRACT: Hill, MW, Roberts, M, Price, MJ, and Kay, AD. Effects of flywheel training with eccentric overload on standing balance, mobility, physical function, muscle thickness, and muscle quality in older adults. J Strength Cond Res 36(11): 3190-3199, 2022-This study investigated the effects of a 6-week eccentric overload flywheel training program on vastus lateralis (VL) and gastrocnemius medialis (GM) muscle thickness and muscle quality (echo intensity), mobility (Timed Up and Go [TUG]), physical function (sit-to-stand), and balance (postural sway) performance. Nineteen subjects were assigned to either a flywheel training group ( n = 11, age = 66.4 ± 5.2 years) or a control group ( n = 8, age = 65.9 ± 3.8 years). The flywheel group underwent twice weekly squat and calf raise exercises for 6 weeks with outcome measures assessed before and after training or a time-matched control period. Throughout the training, subjects were instructed to contract as fast as possible with maximal effort during the concentric phase and to maximally resist the pull during the eccentric phase. The alpha value was a priori set at p < 0.05. Statistically significant ( p < 0.05) mean ( SD ) increases in right and left VL (7.6-9.6 ± 7.7-9.8%) and GM (8.6-8.7 ± 6.4-11.5%) muscle thickness and a reduction in VL (10.2-11.3 ± 5.9-7.9%) and GM (11.7-11.9 ± 5.6-9.6%) echo intensity were accompanied by faster TUG time (13.7 ± 7.0%) improved sit-to-stand performance (17.8-23.5 ± 7.6 - 13.4%) and reduced postural sway (29.7-42.3 ± 13.2-24.2%) after 6 weeks of flywheel training. There were no differences in any outcome measures between the treatment and control group at baseline ( p > 0.05). Overall, we observed substantial gains in muscle thickness and muscle quality, in addition to enhanced physical function, balance, and mobility performance among older adults after flywheel training, which may have important implications for preserving the functional capacity of older adults.

The acute management of ankle fractures (Augment) study: A prospective trainee led national collaborative audit of the Boast 12 guidelines.

BACKGROUND: Ankle fractures are one of the most common fractures in adults aged 20-65 years. The British Orthopaedic Association (BOA) and British Orthopaedic Foot and Ankle Society (BOFAS) jointly produced Standards for Trauma (BOAST) BOAST 12, with the aim of reducing morbidity by standardising care of these injuries. The primary aim of the AUGMENT study was to determine the extent and clinical effect of variation from BOAST 12. METHODS: AUGMENT was a multi-centre prospective trainee led audit of consecutive patients presenting with an ankle fracture within a four-week period. Data were collected on patient demographics, comorbidities, management and 12-week outcome. The BOAST 12 standards were divided into four subgroups; documentation, imaging, management and follow-up. Percentage compliance with each subgroup was analysed. A multivariate logistic regression analysis was used to determine impact of overall compliance on likelihood of discharge in follow-up period. FINDINGS: 971 patients were included across 52 sites. The overall rate of BOAST 12 compliance was 41.7%. Variations in practice were observed in clinical documentation, especially of neurovascular status, (40.7%) and VTE assessment (61.5%). Patient management compliance with all 16 of the BOAST 12 standards was associated with a higher rate of discharge during the 12-week follow-up period (p = 0.005). CONCLUSION: AUGMENT has demonstrated that the management of ankle fractures is variable across the UK. Over half of patients had aspects of their care that were not BOAST 12 compliant. When compliance was observed, it was associated with earlier discharge from orthopaedic care.

Heat-related issues and practical applications for Paralympic athletes at Tokyo 2020.

International sporting competitions, including the Paralympic Games, are increasingly being held in hot and/or humid environmental conditions. Thus, a greater emphasis is being placed on preparing athletes for the potentially challenging environmental conditions of the host cities, such as the upcoming Games in Tokyo in 2020. However, evidence-based practices are limited for the impairment groups that are eligible to compete in Paralympic sport. This review aims to provide an overview of heat-related issues for Paralympic athletes alongside current recommendations to reduce thermal strain and technological advancements in the lead up to the Tokyo 2020 Paralympic Games. When competing in challenging environmental conditions, a number of factors may contribute to an athlete's predisposition to heightened thermal strain. These include the characteristics of the sport itself (type, intensity, duration, modality, and environmental conditions), the complexity and severity of the impairment and classification of the athlete. For heat vulnerable Paralympic athletes, strategies such as the implementation of cooling methods and heat acclimation can be used to combat the increase in heat strain. At an organizational level, regulations and specific heat policies should be considered for several Paralympic sports. Both the utilization of individual strategies and specific heat health policies should be employed to ensure that Paralympics athletes' health and sporting performance are not negatively affected during the competition in the heat at the Tokyo 2020 Paralympic Games.

A multi-genotype therapeutic human papillomavirus vaccine elicits potent T cell responses to conserved regions of early proteins.

Despite an efficacious prophylactic human papillomavirus (HPV) vaccine there is still a considerable global burden of HPV-related disease. Therapeutic vaccines that could prevent cancers in at-risk women are urgently needed. Most candidate therapeutic vaccines have focused on two high-risk (hr) HPV genotypes, 16 and 18, and two viral targets, E6 and E7, which may limit global coverage and efficacy. We designed the synthetic gene '5GHPV3' by selecting conserved regions from each of the six early proteins and generating consensus sequences to represent five hrHPV genotypes. 5GHPV3 was delivered by plasmid DNA, chimpanzee adenovirus (ChAdOx1) and modified vaccinia Ankara (MVA) vectors in prime-boost regimens to mice. ChAdOx1-5GHPV3 / MVA-5GHPV3 induced higher magnitude and more durable HPV-specific T cell responses than other regimens. Vaccine-induced T cells were polyfunctional and persisted at high frequencies for at least six weeks. Importantly, HPV-specific effector CD8 + T cells were detected in the cervix following systemic administration of ChAdOx1-5GHPV3 / MVA-5GHPV3 and increased in frequency over time, indicating continued trafficking of T cells to the cervix. Finally, T cells specific for 5GHPV3 encoded antigens were detected by IFN-γ Elispot in women with current or past hrHPV infections, confirming the presence of epitopes relevant to natural immune control.

An Aspartate-Specific Solute-Binding Protein Regulates Protein Kinase G Activity To Control Glutamate Metabolism in Mycobacteria.

Signaling by serine/threonine phosphorylation controls diverse processes in bacteria, and identification of the stimuli that activate protein kinases is an outstanding question in the field. Recently, we showed that nutrients stimulate phosphorylation of the protein kinase G substrate GarA in Mycobacterium smegmatis and Mycobacterium tuberculosis and that the action of GarA in regulating central metabolism depends upon whether it is phosphorylated. Here we present an investigation into the mechanism by which nutrients activate PknG. Two unknown genes were identified as co-conserved and co-expressed with PknG: their products were a putative lipoprotein, GlnH, and putative transmembrane protein, GlnX. Using a genetic approach, we showed that the membrane protein GlnX is functionally linked to PknG. Furthermore, we determined that the ligand specificity of GlnH matches the amino acids that stimulate GarA phosphorylation. We determined the structure of GlnH in complex with different amino acid ligands (aspartate, glutamate, and asparagine), revealing the structural basis of ligand specificity. We propose that the amino acid concentration in the periplasm is sensed by GlnH and that protein-protein interaction allows transmission of this information across the membrane via GlnX to activate PknG. This sensory system would allow regulation of nutrient utilization in response to changes in nutrient availability. The sensor, signaling, and effector proteins are conserved throughout the Actinobacteria, including the important human pathogen Mycobacterium tuberculosis, industrial amino acid producer Corynebacterium glutamicum, and antibiotic-producing Streptomyces species.IMPORTANCE Tuberculosis (TB) kills 5,000 people every day, and the prevalence of multidrug-resistant TB is increasing in every country. The processes by which the pathogen Mycobacterium tuberculosis senses and responds to changes in its environment are attractive targets for drug development. Bacterial metabolism differs dramatically between growing and dormant cells, and these changes are known to be important in pathogenesis of TB. Here, we used genetic and biochemical approaches to identify proteins that allow M. tuberculosis to detect amino acids in its surroundings so that it can regulate its metabolism. We have also shown how individual amino acids are recognized. The findings have broader significance for other actinobacterial pathogens, such as nontuberculous mycobacteria, as well as Actinobacteria used to produce billions of dollars of amino acids and antibiotics every year.

Technical Note: Direct measurement of continuous TMR data with a 1D tank and automated couch movements.

PURPOSE: Real-time dynamic control of the linear accelerator, couch, and imaging parameters during radiation delivery was investigated as a novel technique for acquiring tissue maximum ratio (TMR) data. METHODS: TrueBeam Developer Mode (Varian Medical Systems, Palo Alto, CA, USA) was used to control the linear accelerator using the Extensible Markup Language (XML). A single XML file was used to dynamically manipulate the machine, couch, and imaging parameters during radiation delivery. A TG-51 compliant 1D water tank was placed on the treatment couch, and used to position a detector at isocenter at a depth of 24.5 cm. A depth scan was performed towards the water surface. Via XML control, the treatment couch vertical position was simultaneously lowered at the same rate, maintaining the detector position at isocenter, allowing for the collection of TMR data. To ensure the detector remained at isocenter during the delivery, the in-room camera was used to monitor the detector. Continuous kV fluoroscopic images during 10 test runs further confirmed this result. TMR data at multiple Source to Detector Distances (SDD) and scan speeds were acquired to investigate their impact on the TMR data. Percentage depth dose (PDD) scans (for conversion to TMR) along with traditional discrete TMR data were acquired as a standard for comparison. RESULTS: More than 99.8% of the measured points had a gamma value (1%/1 mm) < 1 when compared with discrete or PDD converted TMR data. Fluoroscopic images showed that the concurrent couch and tank movements resulted in SDD errors < 1 mm. TMRs acquired at SDDs of 99, 100, and 101 cm showed differences less than 0.004. CONCLUSION: TrueBeam Developer Mode was used to collect continuous TMR data with the same accuracy as traditionally collected discrete data, but yielded higher sampled resolution and reduced acquisition time. This novel method does not require the modification of any equipment and does not use a 3D tank or reservoir.

Thermoregulatory Responses during Competitive Wheelchair Rugby Match Play.

The purpose of this study was to determine whether a player's physical impairment or activity profile was related to the amount of thermal strain experienced during wheelchair rugby match play. 17 elite wheelchair rugby players played a competitive match, whilst activity profiles, measures of core and skin temperature, heart rate and perceptual responses were taken. Players were divided into 2 groups depending on their physical impairment: players with a cervical spinal cord injury, (n=10) or non-spinal related physical impairment (n=7). Total distance was lower (4 842±324 vs. 5 541±316 m, p<0.01, ES=2.2) and mean speed slower (1.13±0.11 vs. 1.27±0.11 m∙s-1, p<0.03, ES=1.3) in players with a spinal cord injury. Yet, the change in core temperature (1.6±0.4 vs. 0.7±0.3°C, p<0.01, ES=2.5) was significantly greater in players with a spinal cord injury. In conclusion, players with a spinal cord injury were under greater thermal strain during wheelchair rugby match play, as a result of their reduced heat loss capacity, due to their physical impairment and not because of their activity profile.

Changes in kinematics and arm-leg coordination during a 100-m breaststroke swim.

The purpose of this study was to compare arm-leg coordination and kinematics during 100 m breaststroke in 26 (8 female; 18 male) specialist breaststroke swimmers. Laps were recorded using three 50-Hz underwater cameras. Heart rate and blood lactate were measured pre- and post-swim. Arm-leg coordination was defined using coordination phases describing continuity between recovery and propulsive phases of upper and lower limbs: coordination phase 1 (time between end of leg kick and start of the arm pull phases); and coordination phase 2 (time between end of arm pull and start of leg kick phases). Duration of stroke phases, coordination phases, swim velocity, stroke length (SL), stroke rate (SR) and stroke index (SI) were analysed during the last three strokes of each lap that were unaffected by turning or finishing. Significant changes in velocity, SI and SL (P < 0.05) were found between laps. Both sexes showed significant increase (P < 0.05) in heart rate and blood lactate pre- to post-swim. Males had significantly (P < 0.01) faster swim velocities resulting from longer SLs (P = 0.016) with no difference in SR (P = 0.064). Sex differences in kinematic parameters can be explained by anthropometric differences providing males with increased propelling efficiency.

The effect of high-intensity cycling training on postural sway during standing under rested and fatigued conditions in healthy young adults.

PURPOSE: The purpose of this study was to investigate whether high-intensity cycling training leads to adapted responses of balance performance in response to exercise-induced muscle fatigue. METHODS: Eighteen healthy adults were assigned to either 3-weeks (n = 8, age 20.1 ± 2.6 years, height 177 ± 5 cm, mass 73.6 ± 5.1 kg) or 6-weeks (n = 10, age 24.3 ± 5.8 years, height 179 ± 6 cm, mass 81.0 ± 15.8 kg) of high-intensity training (HIT) on a cycle ergometer. The centre of pressure (COP) displacement in the anteroposterior (COPAP) direction and COP path length (COPL) were measured before and after the first and final high-intensity training sessions. RESULTS: Pre-training, exercise-induced fatigue elicited an increase in COPAP (3-weeks; p = 0.001, 6-weeks; p = 0.001) and COPL (3-weeks; p = 0.002, 6-weeks; p = 0.001) returning to pre-exercise levels within 10-min of recovery. Following 3-weeks of training, significant increases in COPAP (p = 0.001) and COPL (p = 0.002) were observed post-fatigue, returning to pre-exercise levels after 15-min of recovery. After 6-weeks of training no significant increases in sway (COPAP; p = 0.212, COPL; p = 0.998) were observed following exercise-induced fatigue. CONCLUSIONS: In summary, 3 weeks of HIT resulted in longer recovery times following fatigue compared to pre-training assessments. After 6 weeks of HIT, postural sway following fatigue was attenuated. These results indicate that HIT could be included in injury prevention programmes, however, caution should be taken during early stages of the overreaching process.

Coincidence Anticipation Timing Performance during an Acute Bout of Brisk Walking in Older Adults: Effect of Stimulus Speed.

This study examined coincidence anticipation timing (CAT) performance at slow and fast stimulus speeds before, during, and after an acute bout of walking in adults aged 60-76 years. Results from a series of repeated measures ANOVAs indicated significant rest versus exercise × stimulus speed × time interactions for absolute and variable errors (both P = 0.0001) whereby absolute and variable error scores, when stimulus speed was slow, improved as the duration of exercise increased. When stimulus speed was fast there were significantly greater absolute and variable errors at 18 minutes of the walking bout. There was also greater error at 18 minutes during walking compared to rest. These results suggest that, in a task involving walking and CAT, stimulus speeds plays an important role; specifically walking (exercise) enhances CAT performance at slow stimulus speeds but reduces CAT performance at fast stimulus speeds. The implications are that in everyday situations, where events require dual-task responses to be made at different speeds, for example, walking on the pavement whilst avoiding a crowd, compared to crossing a busy road, an understanding of how different stimulus speeds influence dual-task performance is extremely important, particularly in the older adult population.

Cooling athletes with a spinal cord injury.

Cooling strategies that help prevent a reduction in exercise capacity whilst exercising in the heat have received considerable research interest over the past 3 decades, especially in the lead up to a relatively hot Olympic and Paralympic Games. Progressing into the next Olympic/Paralympic cycle, the host, Rio de Janeiro, could again present an environmental challenge for competing athletes. Despite the interest and vast array of research into cooling strategies for the able-bodied athlete, less is known regarding the application of these cooling strategies in the thermoregulatory impaired spinal cord injured (SCI) athletic population. Individuals with a spinal cord injury (SCI) have a reduced afferent input to the thermoregulatory centre and a loss of both sweating capacity and vasomotor control below the level of the spinal cord lesion. The magnitude of this thermoregulatory impairment is proportional to the level of the lesion. For instance, individuals with high-level lesions (tetraplegia) are at a greater risk of heat illness than individuals with lower-level lesions (paraplegia) at a given exercise intensity. Therefore, cooling strategies may be highly beneficial in this population group, even in moderate ambient conditions (~21 °C). This review was undertaken to examine the scientific literature that addresses the application of cooling strategies in individuals with an SCI. Each method is discussed in regards to the practical issues associated with the method and the potential underlying mechanism. For instance, site-specific cooling would be more suitable for an athlete with an SCI than whole body water immersion, due to the practical difficulties of administering this method in this population group. From the studies reviewed, wearing an ice vest during intermittent sprint exercise has been shown to decrease thermal strain and improve performance. These garments have also been shown to be effective during exercise in the able-bodied. Drawing on additional findings from the able-bodied literature, the combination of methods used prior to and during exercise and/or during rest periods/half-time may increase the effectiveness of a strategy. However, due to the paucity of research involving athletes with an SCI, it is difficult to establish an optimal cooling strategy. Future studies are needed to ensure that research outcomes can be translated into meaningful performance enhancements by investigating cooling strategies under the constraints of actual competition. Cooling strategies that meet the demands of intermittent wheelchair sports need to be identified, with particular attention to the logistics of the sport.

Thermoregulation during intermittent exercise in athletes with a spinal-cord injury.

PURPOSE: Individuals with a spinal-cord injury have impaired thermoregulatory control due to a loss of sudomotor and vasomotor effectors below the lesion level. Thus, individuals with high-level lesions (tetraplegia) possess greater thermoregulatory impairment than individuals with lower-level lesions (paraplegia). Previous research has not reflected the intermittent nature and modality of wheelchair court sports or replicated typical environmental temperatures. Hence, the purpose of this study was to investigate the thermoregulatory responses of athletes with tetraplegia and paraplegia during an intermittent-sprint protocol (ISP) and recovery in cool conditions. METHODS: Sixteen wheelchair athletes, 8 with tetraplegia (TP, body mass 65.2±4.4 kg) and 8 with paraplegia (body mass 68.1±12.3 kg), completed a 60-min ISP in 20.6°C±0.1°C, 39.6%±0.8% relative humidity on a wheelchair ergometer, followed by 15 min of passive recovery. Core temperature (Tcore) and mean (Tsk) and individual skin temperatures were measured throughout. RESULTS: Similar external work (P=.70, ES=0.20) yet a greater Tcore (P<.05, ES=2.27) and Tsk (P<.05, ES=1.50) response was demonstrated by TP during the ISP. CONCLUSIONS: Despite similar external work, a marked increase in Tcore in TP during exercise and recovery signifies that thermoregulatory differences between the groups were predominantly due to differences in heat loss. Further increases in thermal strain were not prevented by the active and passive recovery between maximal-effort bouts of the ISP, as Tcore continually increased throughout the protocol in TP.

Real-time simulator for designing electron dual scattering foil systems.

The purpose of this work was to develop a user friendly, accurate, real-time com- puter simulator to facilitate the design of dual foil scattering systems for electron beams on radiotherapy accelerators. The simulator allows for a relatively quick, initial design that can be refined and verified with subsequent Monte Carlo (MC) calculations and measurements. The simulator also is a powerful educational tool. The simulator consists of an analytical algorithm for calculating electron fluence and X-ray dose and a graphical user interface (GUI) C++ program. The algorithm predicts electron fluence using Fermi-Eyges multiple Coulomb scattering theory with the reduced Gaussian formalism for scattering powers. The simulator also estimates central-axis and off-axis X-ray dose arising from the dual foil system. Once the geometry of the accelerator is specified, the simulator allows the user to continuously vary primary scattering foil material and thickness, secondary scat- tering foil material and Gaussian shape (thickness and sigma), and beam energy. The off-axis electron relative fluence or total dose profile and central-axis X-ray dose contamination are computed and displayed in real time. The simulator was validated by comparison of off-axis electron relative fluence and X-ray percent dose profiles with those calculated using EGSnrc MC. Over the energy range 7-20 MeV, using present foils on an Elekta radiotherapy accelerator, the simulator was able to reproduce MC profiles to within 2% out to 20 cm from the central axis. The central-axis X-ray percent dose predictions matched measured data to within 0.5%. The calculation time was approximately 100 ms using a single Intel 2.93 GHz processor, which allows for real-time variation of foil geometrical parameters using slider bars. This work demonstrates how the user-friendly GUI and real-time nature of the simulator make it an effective educational tool for gaining a better understanding of the effects that various system parameters have on a relative dose profile. This work also demonstrates a method for using the simulator as a design tool for creating custom dual scattering foil systems in the clinical range of beam energies (6-20 MeV). 

The effects of maximal and submaximal arm crank ergometry and cycle ergometry on postural sway.

Abstract This study aimed to determine whether arm crank ergometry (ACE) disturbed postural sway to the same extent as cycle ergometry (CE). Nine healthy, none specifically trained adults undertook posturographic tests before and after five separate exercise trials consisting of: two incremental exercise tests to exhaustion for ACE and CE to examine postural sway responses to maximal exercise and to determine peak power output (W max); two subsequent tests of 30 min duration for ACE and CE at a relative workload corresponding to 50% of the ergometer-specific W max (ACErel; 53 ± 8 W and CErel; 109 ± 16 W). A final CE trial was performed at the same absolute power output (CEabs) as the submaximal ACE trial to match absolute exercise intensity (i.e., 53 ± 8 W). The centre of pressure (COP) displacement was recorded using a force platform before, immediately after exercise and during a 30-min recovery period. ACE had no effects on postural sway (P > 0.05). An increase in mediolateral COP displacement was observed following maximal CE only (P = 0.001), while anteroposterior COP displacement and COP path length increased following maximal and submaximal CE (P < 0.05). These differences in postural sway according to exercise mode likely stem from the activity of postural muscles when considering that CE recruits lower limb muscles involved in balance. This study provides evidence of an exercise mode which does not elicit post-exercise balance impairments, therefore possesses applications to those at an increased risk of falling.

The effect of sodium bicarbonate ingestion on back squat and bench press exercise to failure.

This study examined the acute effects of NaHCO3 ingestion on repetitions to failure and rating of perceived exertion in the back squat and bench press in trained men. Eight resistance-trained men took part in this double-blind, randomized crossover experimental study whereby they ingested NaHCO3 (0.3 g·kg(-1) body mass) or placebo (sodium chloride NaCl: 0.045 g·kg(-1) body mass) solution 60 minutes before completing a bout of resistance exercise (3 sets of bench press and back squat exercise to failure at an intensity of 80% 1 repetition maximum). Experimental conditions were separated by at least 48 hours. Participants completed more repetitions to failure in the back squat after NaHCO3 ingestion (p = 0.04) but not for bench press (p = 0.679). Mean ± SD of total repetitions was 31.3 ± 15.3 and 24.6 ± 16.2 for back squat and 28.7 ± 12.2 and 26.7 ± 10.2 for bench press in NaHCO3 and placebo conditions, respectively. Repetitions to failure decreased as set increased for the back squat and bench press (p = 0.001, both). Rating of perceived exertion significantly increased with set for the back squat and bench press (p = 0.002, both). There was no significant change in blood lactate across time or between conditions. There were however treatment × time interactions for blood pH (p = 0.014) and blood HCO3 concentration (p = 0.001). After ingestion, blood pH and HCO3 (p = 0.008) concentrations were greater for the NaHCO3 condition compared with the placebo condition (p < 0.001). The results of this study suggest that sodium bicarbonate ingestion can enhance resistance exercise performance using a repetition to failure protocol in the first exercise in a resistance exercise session.

Molecular characterization and evolution of self-incompatibility genes in Arabidopsis thaliana: the case of the Sc haplotype.

The switch from an outcrossing mode of mating enforced by self-incompatibility to self-fertility in the Arabidopsis thaliana lineage was associated with mutations that inactivated one or both of the two genes that comprise the self-incompatibility (SI) specificity-determining S-locus haplotype, the S-locus receptor kinase (SRK) and the S-locus cysteine-rich (SCR) genes, as well as unlinked modifier loci required for SI. All analyzed A. thaliana S-locus haplotypes belong to the SA, SB, or SC haplotypic groups. Of these three, the SC haplotype is the least well characterized. Its SRKC gene can encode a complete open-reading frame, although no functional data are available, while its SCRC sequences have not been isolated. As a result, it is not known what mutations were associated with inactivation of this haplotype. Here, we report on our analysis of the Lz-0 accession and the characterization of its highly rearranged SC haplotype. We describe the isolation of its SCRC gene as well as the subsequent isolation of SCRC sequences from other SC-containing accessions and from the A. lyrata S36 haplotype, which is the functional equivalent of the A. thaliana SC haplotype. By performing transformation experiments using chimeric SRK and SCR genes constructed with SC- and S36-derived sequences, we show that the SRKC and SCRC genes of Lz-0 and at least a few other SC-containing accessions are nonfunctional, despite SCRC encoding a functional full-length protein. We identify the probable mutations that caused the inactivation of these genes and discuss our results in the context of mechanisms of S-locus inactivation in A. thaliana.