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.

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.

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 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.

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.

Potential of discrete Gaussian edge feathering method for improving abutment dosimetry in eMLC-delivered segmented-field electron conformal therapy.

PURPOSE: The purpose of this work was to investigate the potential of discrete Gaussian edge feathering of the higher energy electron fields for improving abutment dosimetry in the planning volume when using an electron multileaf collimator (eMLC) to deliver segmented-field electron conformal therapy (ECT). METHODS: A discrete (five-step) Gaussian edge spread function was used to match dose penumbras of differing beam energies (6-20 MeV) at a specified depth in a water phantom. Software was developed to define the leaf eMLC positions of an eMLC that most closely fit each electron field shape. The effect of 1D edge feathering of the higher energy field on dose homogeneity was computed and measured for segmented-field ECT treatment plans for three 2D PTVs in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of the x-axis (parallel to leaf motion) and remained constant along the y-axis (perpendicular to leaf motion). Additionally, the effect of 2D edge feathering was computed and measured for one radially symmetric, 3D PTV in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of both axes. For the 3D PTV, the feathering scheme was evaluated for 0.1-1.0-cm leaf widths. Dose calculations were performed using the pencil beam dose algorithm in the Pinnacle(3) treatment planning system. Dose verification measurements were made using a prototype eMLC (1-cm leaf width). RESULTS: 1D discrete Gaussian edge feathering reduced the standard deviation of dose in the 2D PTVs by 34, 34, and 39%. In the 3D PTV, the broad leaf width (1 cm) of the eMLC hindered the 2D application of the feathering solution to the 3D PTV, and the standard deviation of dose increased by 10%. However, 2D discrete Gaussian edge feathering with simulated eMLC leaf widths of 0.1-0.5 cm reduced the standard deviation of dose in the 3D PTV by 33-28%, respectively. CONCLUSIONS: A five-step discrete Gaussian edge spread function applied in 2D improves the abutment dosimetry but requires an eMLC leaf resolution better than 1 cm.

Dose perturbation due to the polysulfone cap surrounding a Fletcher-Williamson colpostat.

We conducted a metrological evaluation of the dosimetric impact due to the polysulfone cap used with the Fletcher-Williamson (FW) colpostat for 192Ir high-dose rate and pulsed-dose rate intracavitary brachytherapy using Monte Carlo simulations. Polysulfone caps with diameter of 30 mm, 25 mm, 20 mm, and 16 mm (mini-ovoid) were simulated and the absorbed dose rate in the surrounding water was calculated and compared to the dose rate for a bare 192Ir source in water. The dose perturbation depended on the cap diameter, distance away from the cap surface, and angular position around the cap. The largest dose rate reductions were found to be in the direction of the tumor bed where the cap is thickest. The range of perturbation over all depths and cap diameters was +2.8% (dose enhancement) to -6.8% (dose reduction). The FW colpostat cap's material composition should be modified to reduce this dosimetric effect or brachytherapy treatment planning dose algorithms should be improved to account for this perturbation.

The effect of sodium bicarbonate ingestion on high-intensity intermittent running and subsequent performance.

The purpose of this study was to determine the effects of sodium bicarbonate (NaHCO3) ingestion on intermittent running and subsequent performance. Eight healthy men volunteered to take part in the study. One hour after the ingestion of either NaHCO(3) or placebo (sodium chloride; NaCl) participants undertook 20 x 24-second runs on a motorized treadmill at the velocity eliciting maximal oxygen uptake (100% v-VO(2)max). After sprint 20 participants performed a run to volitional exhaustion at 120% v-VO(2)max. Capillary blood samples for blood pH, bicarbonate ([HCO(3)]), and lactate ([Bla]) concentration were taken pre and postingestion, every fifth sprint and after the performance run. After ingestion of NaHCO(3), blood [HCO(3)] increased from resting values (p < 0.05), and the increase in pH approached significance. Blood [HCO(3)(-)] continually decreased throughout intermittent exercise (p < 0.05) and decreased further after performance in both trials (p < 0.05). [Bla] was similar in both trials throughout intermittent exercise but was greater at exhaustion for NaHCO(3) (main effect for trial; p < 0.05). There was no significant difference in performance of the group between trials (78 +/- 22 and 75 +/- 22 seconds for NaHCO(3) and NaCl, respectively). The intercept of the relationships between [Bla] and [HCO(3)(-)] and between [Bla] and pH was greater during NaHCO(3) (p < 0.05), whereas the relationship between pH and [HCO(3)(-)] was unchanged (p > 0.05). The results of this study suggest that the ingestion of NaHCO(3) before intermittent type exercise was sufficient to induce metabolic alkalosis but did not significantly affect performance. However, because significant individual variations in performance were observed, an individual approach to bicarbonate ingestion is recommended based on the intensity and duration of the required performance.

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.

Development of prototype shielded cervical intracavitary brachytherapy applicators compatible with CT and MR imaging.

PURPOSE: Intracavitary brachytherapy (ICBT) is an integral part of the treatment regimen for cervical cancer and, generally, outcome in terms of local disease control and complications is a function of dose to the disease bed and critical structures, respectively. Therefore, it is paramount to accurately determine the dose given via ICBT to the tumor bed as well as critical structures. This is greatly facilitated through the use of advanced three-dimensional imaging modalities, such as CT and MR, to delineate critical and target structures with an ICBT applicator inserted in vivo. These methods are not possible when using a shielded applicator due to the image artifacts generated by interovoid shielding. The authors present two prototype shielded ICBT applicators that can be utilized for artifact-free CT image acquisition. They also investigate the MR amenability and dosimetry of a novel tungsten-alloy shielding material to extend the functionality of these devices. METHODS: To accomplish artifact-free CT image acquisition, a "step-and-shoot" (S&S) methodology was utilized, which exploits the prototype applicators movable interovoid shielding. Both prototypes were placed in imaging phantoms that positioned the applicators in clinically applicable orientations. CT image sets were acquired of the prototype applicators as well as a shielded Fletcher-Williamson (sFW) ovoid. Artifacts present in each CT image set were qualitatively compared for each prototype applicator following the S&S methodology and the sFW. To test the novel tungsten-alloy shielding material's MR amenability, they constructed a phantom applicator that mimics the basic components of an ICBT ovoid. This phantom applicator positions the MR-compatible shields in orientations equivalent to the sFW bladder and rectal shields. MR images were acquired within a gadopentetate dimeglumine-doped water tank using standard pulse sequences and examined for artifacts. In addition, Monte Carlo simulations were performed to match the attenuation due to the thickness of this new shield type with current, clinically utilized ovoid shields and a 192Ir HDR/PDR source. RESULTS: Artifact-free CT images could be acquired of both generation applicators in a clinically applicable geometry using the S&S method. MR images were acquired of the phantom applicator containing shields, which contained minimal, clinically relevant artifacts. The thickness required to match the dosimetry of the MR-compatible and sFW rectal shields was determined using Monte Carlo simulations. CONCLUSIONS: Utilizing a S&S imaging method in conjunction with prototype applicators that feature movable interovoid shields, they were able to acquire artifact-free CT image sets in a clinically applicable geometry. MR images were acquired of a phantom applicator that contained shields composed of a novel tungsten alloy. Artifacts were largely limited to regions within the ovoid cap and are of no clinical interest. The second generation A3 utilizes this material for interovoid shielding.

Monte Carlo model for a prototype CT-compatible, anatomically adaptive, shielded intracavitary brachytherapy applicator for the treatment of cervical cancer.

PURPOSE: Current, clinically applicable intracavitary brachytherapy applicators that utilize shielded ovoids contain a pair of tungsten-alloy shields which serve to reduce dose delivered to the rectum and bladder during source afterloading. After applicator insertion, these fixed shields are not necessarily positioned to provide optimal shielding of these critical structures due to variations in patient anatomies. The authors present a dosimetric evaluation of a novel prototype intracavitary brachytherapy ovoid [anatomically adaptive applicator (A3)], featuring a single shield whose position can be adjusted with two degrees of freedom: Rotation about and translation along the long axis of the ovoid. METHODS: The dosimetry of the device for a HDR 192Ir was characterized using radiochromic film measurements for various shield orientations. A MCNPX Monte Carlo model was developed of the prototype ovoid and integrated with a previously validated model of a v2 mHDR 192Ir source (Nucletron Co.). The model was validated for three distinct shield orientations using film measurements. RESULTS: For the most complex case, 91% of the absolute simulated and measured dose points agreed within 2% or 2 mm and 96% agreed within 10% or 2 mm. CONCLUSIONS: Validation of the Monte Carlo model facilitates future investigations into any dosimetric advantages the use of the A3 may have over the current state of art with respect to optimization and customization of dose delivery as a function of patient anatomical geometries.

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.

Optimization of deterministic transport parameters for the calculation of the dose distribution around a high dose-rate 192Ir brachytherapy source.

The goal of this work was to calculate the dose distribution around a high dose-rate 192Ir brachytherapy source using a multi-group discrete ordinates code and then to compare the results with a Monte Carlo calculated dose distribution. The unstructured tetrahedral mesh discrete ordinates code Attila version 6.1.1 was used to calculate the photon kerma rate distribution in water around the Nucletron microSelectron mHDRv2 source. MCNPX 2.5.c was used to compute the Monte Carlo water photon kerma rate distribution. Two hundred million histories were simulated, resulting in standard errors of the mean of less than 3% overall. The number of energy groups, S(n) (angular order), P(n) (scattering order), and mesh elements were varied in addition to the method of analytic ray tracing to assess their effects on the deterministic solution. Water photon kerma rate matrices were exported from both codes into an in-house data analysis software. This software quantified the percent dose difference distribution, the number of points within +/- 3% and +/- 5%, and the mean percent difference between the two codes. The data demonstrated that a 5 energy-group cross-section set calculated results to within 0.5% of a 15 group cross-section set. S12 was sufficient to resolve the solution in angle. P2 expansion of the scattering cross-section was necessary to compute accurate distributions. A computational mesh with 55 064 tetrahedral elements in a 30 cm diameter phantom resolved the solution spatially. An efficiency factor of 110 with the above parameters was realized in comparison to MC methods. The Attila code provided an accurate and efficient solution of the Boltzmann transport equation for the mHDRv2 source.