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Although significant progress has been made in understanding the cortical correlates underlying balance control, these studies focused on a single task, limiting the ability to generalize the findings. Different balance tasks may elicit cortical activations in the same regions but show different levels of activation because of distinct underlying mechanisms. In this study, twenty young, neurotypical adults were instructed to maintain standing balance while the standing support surface was either translated or rotated. The differences in cortical activations in the frontocentral region between these two widely used tasks were examined using electroencephalography (EEG). Additionally, the study investigated whether transcranial magnetic stimulation could modulate these cortical activations during the platform translation task. Higher delta and lower alpha relative power were found over the frontocentral region during the platform translation task when compared to the platform rotation task, suggesting greater engagement of attentional and sensory integration resources for the former. Continuous theta burst stimulation over the supplementary motor area significantly reduced delta activity in the frontocentral region but did not alter alpha activity during the platform translation task. The results provide a direct comparison of neural activations between two commonly used balance tasks and are expected to lay a strong foundation for designing neurointerventions for balance improvements with effects generalizable across multiple balance scenarios.

Introduction: Interruptions during dental treatment are frequent, and often impact provider satisfaction and processing times We investigate the source and duration of such interruptions at a German dental clinic., Methods: A pre-post approach was adopted at this dental clinic. This included direct observations of 3 dentists and 3 dental hygienists, and a survey of providers. Following that, an intervention (switchable 'Do Not Enter' sign) was chosen, and a pilot study was conducted to evaluate if the chosen intervention can reduce processing time and improve provider satisfaction. Additional observations and surveys were performed afterwards., Results: Pre-intervention data indicated that interruptions have the highest negative impact on provider satisfaction at this clinic as well as on processing time during longer and more complex treatments, where a minor error due to an interruption could lead to rework of 30 minutes and more. The total number of interruptions dropped by 72.5% after the intervention, short interruptions (< 1min) by 86%. Provider survey indicated improvement due to the intervention in perceived workload, provider work satisfaction, patient safety and stress., Conclusions: This study demonstrates that a switchable sign can substantially reduce the number of interruptions in this dental clinic. It also shows the potential of improving the work environment by reducing interruptions to the dental providers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ziegler, Parikh. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The total time of radiation treatment delivery for pancreatic cancer patients with daily online adaptive radiation therapy (ART) on an MR-Linac can range from 50 to 90 min. During this period, the target and normal tissues undergo changes due to respiration and physiologic organ motion. We evaluated the dosimetric impact of the intrafraction physiological organ changes., Methods: Ten locally advanced pancreatic cancer patients were treated with 50 Gy in five fractions with intensity-modulated respiratory-gated radiation therapy on a 0.35-T MR-Linac. Patients received both pre- and post-treatment volumetric MRIs for each fraction. Gastrointestinal organs at risk (GI-OARs) were delineated on the pre-treatment MRI during the online ART process and retrospectively on the post-treatment MRI. The treated dose distribution for each adaptive plan was assessed on the post-treatment anatomy. Prescribed dose volume histogram metrics for the scheduled plan on the pre-treatment anatomy, the adapted plan on the pre-treatment anatomy, and the adapted plan on post-treatment anatomy were compared to the OAR-defined criteria for adaptation: the volume of the GI-OAR receiving greater than 33 Gy (V33Gy) should be ≤1 cubic centimeter., Results: Across the 50 adapted plans for the 10 patients studied, 70% were adapted to meet the duodenum constraint, 74% for the stomach, 12% for the colon, and 48% for the small bowel. Owing to intrafraction organ motion, at the time of post-treatment imaging, the adaptive criteria were exceeded for the duodenum in 62% of fractions, the stomach in 36%, the colon in 10%, and the small bowel in 48%. Compared to the scheduled plan, the post-treatment plans showed a decrease in the V33Gy, demonstrating the benefit of plan adaptation for 66% of the fractions for the duodenum, 95% for the stomach, 100% for the colon, and 79% for the small bowel., Conclusion: Post-treatment images demonstrated that over the course of the adaptive plan generation and delivery, the GI-OARs moved from their isotoxic low-dose region and nearer to the dose-escalated high-dose region, exceeding dose-volume constraints. Intrafraction motion can have a significant dosimetric impact; therefore, measures to mitigate this motion are needed. Despite consistent intrafraction motion, plan adaptation still provides a dosimetric benefit., Competing Interests: JC and JA report travel expenses from ViewRay outside of this work. PP and JD report grants, honoraria and travel expenses from ViewRay outside of this work. PP has clinical research funding from Speakers Board, ViewRay and ownership interest in Nuvaira, neither are related to this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rusu, Cunningham, Arch, Chetty, Parikh and Dolan.)

Introduction: This study investigated kinematic and EMG changes in gait across simulated gravitational unloading levels between 100% and 20% of normal body weight. This study sought to identify if each level of unloading elicited consistent changes-particular to that percentage of normal body weight-or if the changes seen with unloading could be influenced by the previous level(s) of unloading. Methods: 15 healthy adult participants (26.3 ± 2.5 years; 53% female) walked in an Alter-G anti-gravity treadmill unloading system (mean speed: 1.49 ± 0.37 mph) for 1 min each at 100%, 80%, 60%, 40% and 20% of normal body weight, before loading back to 100% in reverse order. Lower-body kinematic data were captured by inertial measurement units, and EMG data were collected from the rectus femoris, biceps femoris, medial gastrocnemius, and anterior tibialis. Data were compared across like levels of load using repeated measures ANOVA and statistical parametric mapping. Difference waveforms for adjacent levels were created to examine the rate of change between different unloading levels. Results: This study found hip, knee, and ankle kinematics as well as activity in the rectus femoris, and medial gastrocnemius were significantly different at the same level of unloading, having arrived from a higher, or lower level of unloading. There were no significant changes in the kinematic difference waveforms, however the waveform representing the change in EMG between 100% and 80% load was significantly different from all other levels. Discussion: This study found that body weight unloading from 100% to 20% elicited distinct responses in the medial gastrocnemius, as well as partly in the rectus femoris. Hip, knee, and ankle kinematics were also affected differentially by loading and unloading, especially at 40% of normal body weight. These findings suggest the previous level of gravitational load is an important factor to consider in determining kinematic and EMG responses to the current level during loading and unloading below standard g. Similarly, the rate of change in kinematics from 100% to 20% appears to be linear, while the rate of change in EMG was non-linear. This is of particular interest, as it suggests that kinematic and EMG measures decouple with unloading and may react to unloading uniquely., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Malaya, Parikh, Smith, Riaz, Chandrasekaran and Layne.)

Purpose: Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) with optional online adaptation has shown promise in delivering ablative doses to unresectable primary liver cancer. However, there remain limited data on the indications for online adaptation as well as dosimetric and longer-term clinical outcomes following MRgSBRT., Methods and Materials: Patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CCA) who completed MRgSBRT to 50 Gy in 5 fractions between June of 2015 and December of 2021 were analyzed. The necessity of adaptive techniques was evaluated. The cumulative incidence of local progression was evaluated and survival and competing risk analyses were performed., Results: Ninety-nine analyzable patients completed MRgSBRT during the study period and 54 % had planning target volumes (PTVs) within 1 cm of the duodenum, small bowel, or stomach at the time of simulation. Online adaptive RT was used in 53 % of patients to correct organ-at-risk constraint violation and/or to improve target coverage. In patients who underwent adaptive RT planning, online replanning resulted in superior target coverage when compared to projected, non-adaptive plans (median coverage ≥ 95 % at 47.5 Gy: 91 % [IQR: 82-96] before adaptation vs 95 % [IQR: 87-99] after adaptation, p < 0.01). The median follow-up for surviving patients was 34.2 months for patients with HCC and 10.1 months for patients with CCA/cHCC-CCA. For all patients, the 2-year cumulative incidence of local progression was 9.8 % (95 % CI: 1.5-18 %) for patients with HCC and 9.0 % (95 % CI: 0.1-18) for patients with CCA/cHCC-CCA. Grade 3 through 5 acute and late clinical gastrointestinal toxicities were observed in < 10 % of the patients., Conclusions: MRgSBRT, with the option for online adaptive planning when merited, allows delivery of ablative doses to primary liver tumors with excellent local control with acceptable toxicities. Additional studies evaluating the efficacy and safety of MRgSBRT in the treatment of primary liver cancer are warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose/objective: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology., Materials/methods: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems., Results: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses., Conclusions: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35  T -MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy., Competing Interests: Michael Chuong reports grants and personal fees from ViewRay; personal fees and non-financial support from Accuray and Sirtex; participates on an advisory board for ViewRay. Mary Ann Clark and Martin Fuss are employees and shareholders of ViewRay, Inc. Lauren E. Henke reports consulting fees from ViewRay, Inc. and Radialogica and grants and other from Varian Medical Systems. Amar Kishan has a grant with ASTRO-PCF, consulting fees and honoraria paid by Varian Medical Systems, Inc. and ViewRay, Inc., shareholder of ViewRay, Inc. Lorraine Portelance has a consulting contract with ViewRay, Inc.Parag J. Parikh reports stock and other ownership of Nuvaira, honoraria, speakers’ bureau from ViewRay, and research funding from ViewRay. Michael F. Bassetti has a research grant from Astra Zeneca and royalties or licenses from National Jewish Hospital (Bcl3 antibody and Spi2A antibody). Himanshu Nagar participates on advisory boards for Bristol Meyers Squibb and ViewRay, Inc. Stephen A. Rosenberg participates on ViewRay medical advisory boards, Lung Research Consortium (both non-compensated), and has research grants from ViewRay; consulting fees paid by Novocure. Minesh Mehta has consulting fees from Karyopharm, Sapience, Zap, Mevion, Xoft, Tocagen; he is on the Board of Directors of Oncoceutics and owns stock in Oncoceutics and Chimerix. Bassem I. Zaki received manuscript support from ViewRay, Inc. and is a member of the ASTRO guideline subcommittee. Tamer Refaat reports nothing to disclose. Justin Rineer reports nothing to disclose. Adam Smith reports nothing to disclose. Steven Seung reports nothing to disclose. Bassem I. Zaki reports leadership role on ASTRO’s Guidelines Committee. Raymond H. Mak reports grants from ViewRay; consulting fees from ViewRay and Astra Zeneca., (© 2022 The Author(s).)

Naturally occurring postural instabilities that occur while standing and walking elicit specific cortical responses in the fronto-central regions (N1 potentials) followed by corrective balance responses to prevent falling. However, no framework could simultaneously track different biomechanical parameters preceding N1s, predict N1s, and assess their predictive power. Here, we propose a framework and show its utility by examining cortical activity (through electroencephalography [EEG]), ground reaction forces, and head acceleration in the anterior-posterior (AP) direction. Ten healthy young adults carried out a balance task of standing on a support surface with or without sway referencing in the AP direction, amplifying, or dampening natural body sway. Using independent components from the fronto-central cortical region obtained from subject-specific head models, we first robustly validated a prior approach on identifying low-amplitude N1 potentials before early signs of balance corrections. Then, a machine learning algorithm was used to evaluate different biomechanical parameters obtained before N1 potentials, to predict the occurrence of N1s. When different biomechanical parameters were directly compared, the time to boundary (TTB) was found to be the best predictor of the occurrence of upcoming low-amplitude N1 potentials during a balance task. Based on these findings, we confirm that the spatio-temporal characteristics of the center of pressure (COP) might serve as an essential parameter that can facilitate the early detection of postural instability in a balance task. Extending our framework to identify such biomarkers in dynamic situations like walking might improve the implementation of corrective balance responses through brain-machine-interfaces to reduce falls in the elderly.

Importance: Predicting outcomes in patients receiving neoadjuvant therapy for rectal cancer is challenging because of tumor downstaging. Validated clinical calculators that can estimate recurrence-free survival (RFS) and overall survival (OS) among patients with rectal cancer who have received multimodal therapy are needed., Objective: To develop and validate clinical calculators providing estimates of rectal cancer recurrence and survival that are better for individualized decision-making than the American Joint Committee on Cancer (AJCC) staging system or the neoadjuvant rectal (NAR) score., Design, Setting, and Participants: This prognostic study developed risk models, graphically represented as nomograms, for patients with incomplete pathological response using Cox proportional hazards and multivariable regression analyses with restricted cubic splines. Because patients with complete pathological response to neoadjuvant therapy had uniformly favorable outcomes, their predictions were obtained separately. The study included 1400 patients with stage II or III rectal cancer who received treatment with chemotherapy, radiotherapy, and surgery at 2 comprehensive cancer centers (Memorial Sloan Kettering [MSK] Cancer Center and Siteman Cancer Center [SCC]) between January 1, 1998, and December 31, 2017. Patients from the MSK cohort received chemoradiation, surgery, and adjuvant chemotherapy from January 1, 1998, to December 31, 2014; these patients were randomly assigned to either a model training group or an internal validation group. Models were externally validated using data from the SCC cohort, who received either chemoradiation, surgery, and adjuvant chemotherapy (chemoradiotherapy group) or short-course radiotherapy, consolidation chemotherapy, and surgery (total neoadjuvant therapy with short-course radiotherapy group) from January 1, 2009, to December 31, 2017. Data were analyzed from March 1, 2020, to January 10, 2021., Exposures: Chemotherapy, radiotherapy, chemoradiotherapy, and surgery., Main Outcomes and Measures: Recurrence-free survival and OS were the outcome measures, and the discriminatory performance of the clinical calculators was measured with concordance index and calibration plots. The ability of the clinical calculators to predict RFS and OS was compared with that of the AJCC staging system and the NAR score. The models for RFS and OS among patients with incomplete pathological response included postoperative pathological tumor category, number of positive lymph nodes, tumor distance from anal verge, and large- and small-vessel venous and perineural invasion; age was included in the risk model for OS. The final clinical calculators provided RFS and OS estimates derived from Kaplan-Meier curves for patients with complete pathological response and from risk models for patients with incomplete pathological response., Results: Among 1400 total patients with locally advanced rectal cancer, the median age was 57.8 years (range, 18.0-91.9 years), and 863 patients (61.6%) were male, with tumors at a median distance of 6.7 cm (range, 0-15.0 cm) from the anal verge. The MSK cohort comprised 1069 patients; of those, 710 were assigned to the model training group and 359 were assigned to the internal validation group. The SCC cohort comprised 331 patients; of those, 200 were assigned to the chemoradiotherapy group and 131 were assigned to the total neoadjuvant therapy with short-course radiotherapy group. The concordance indices in the MSK validation data set were 0.70 (95% CI, 0.65-0.76) for RFS and 0.73 (95% CI, 0.65-0.80) for OS. In the external SCC data set, the concordance indices in the chemoradiotherapy group were 0.71 (95% CI, 0.62-0.81) for RFS and 0.72 (95% CI, 0.59-0.85) for OS; the concordance indices in the total neoadjuvant therapy with short-course radiotherapy group were 0.62 (95% CI, 0.49-0.75) for RFS and 0.67 (95% CI, 0.46-0.84) for OS. Calibration plots confirmed good agreement between predicted and observed events. These results compared favorably with predictions based on the AJCC staging system (concordance indices for MSK validation: RFS = 0.69 [95% CI, 0.64-0.74]; OS = 0.67 [95% CI, 0.58-0.75]) and the NAR score (concordance indices for MSK validation: RFS = 0.56 [95% CI, 0.50-0.63]; OS = 0.56 [95% CI, 0.46-0.66]). Furthermore, the clinical calculators provided more individualized outcome estimates compared with the categorical schemas (eg, estimated RFS for patients with AJCC stage IIIB disease ranged from 7% to 68%)., Conclusions and Relevance: In this prognostic study, clinical calculators were developed and validated; these calculators provided more individualized estimates of the likelihood of RFS and OS than the AJCC staging system or the NAR score among patients with rectal cancer who received multimodal treatment. The calculators were easy to use and applicable to both short- and long-course radiotherapy regimens, and they may be used to inform surveillance strategies and facilitate future clinical trials and statistical power calculations.

Explicit knowledge of object center of mass or CM location fails to guide anticipatory scaling of digit forces necessary for dexterous manipulation. We previously showed that allowing young adults to choose where to grasp the object entailed an ability to use arbitrary color cues about object CM location to gradually minimize object tilt across several trials. This conditional learning was achieved through accurate anticipatory modulation of digit position using the color cues. However, it remains unknown how aging affects the ability to use explicit color cues about object CM location to modulate digit placement for dexterous manipulation. We instructed healthy older and young adults to learn a manipulation task using arbitrary color cues about object CM location. Subjects were required to exert clockwise, counterclockwise, or no torque on the object according to the color cue and lift the object while minimizing its tilt. Older adults produced larger torque error during conditional learning trials, resulting in a slower rate of learning than young adults. Importantly, older adults showed impaired anticipatory modulation of digit position when information of the CM location was available via explicit color cues. The older adults also did not modulate their digit forces to compensate for this impairment. Interestingly, however, anticipatory modulation of digit position was intact in the same individuals when information of object CM location was implicitly conveyed from trial-to-trial. We discuss our findings in relation to age-dependent changes in processes and neural network essential for learning dexterous manipulation using arbitrary color cue about object property. NEW & NOTEWORTHY We studied whether older adults are able to predictively modulate digit position using arbitrary color cues indicating object center of mass location for dexterous manipulation. Older adults showed an impaired ability to modulate digit position using the color cues when compared with young adults. Interestingly, similar impairments were not found when same older individuals learned the task using implicit knowledge. Our findings suggest an age-related impairment specifically in the conditional learning mechanisms for dexterous manipulation.

Introduction: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC., Methods: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications., Results: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed., Conclusions: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial., Competing Interests: LaD: Licensing agreement with Research, funds paid to institution. SR: Consults for Novocure Gani: University Hospital Tübingen receives financial and technical support including costs for travels and symposia from Elekta AB (Stockholm, Sweden) under a research agreement. The department of radiation oncology at the Medical College of Wisconsin receives research funding from Elekta AB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hall, Small, Paulson, Koay, Crane, Intven, Daamen, Meijer, Heerkens, Bassetti, Rosenberg, Aitken, Myrehaug, Dawson, Lee, Gani, Chuong, Parikh and Erickson.)

Gait is one of the fundamental behaviors we use to interact with the world. The functionality of the locomotor system is thus related to enriching interactions with our environment. The posterior parietal cortex (PPC) has been found to contribute to motor adaptation during both visuomotor and postural adaptation tasks. Additionally, structural or functional deficits of the PPC lead to impairments in gaits such as shortened steps and increased step width. Based on the aforementioned roles of the PPC, and the importance of gait adaptability, the current investigation sought to identify the role of the PPC in gait adaptation. To achieve this, we performed transcranial direct current stimulation (tDCS) over the bilateral PPC before performing a split-belt treadmill gait adaptation paradigm. We used three stimulation conditions in a within-subject design. tDCS was administered in a randomized and double-blinded order. Following each stimulation session, subjects first performed baseline walking with both belts running at the same speed. Then, subjects walked for 15 min on an uncoupled treadmill, with the belts being driven at a 3:1 speed ratio. Last, they returned to normal (i.e., tied-belt) walking for 5 min. Results from 15 young and healthy subjects identified that subjects required more steps to adapt to split-belt walking following the suppression of the left hemisphere PPC, contralateral to the fast belt. Furthermore, while suppression of the left hemisphere PPC did not increase the number of steps required to re-adapt to tied-belt walking, this condition did lead to increased magnitude of after-effects. Together, these findings indicate that the PPC is involved in locomotor adaptation. These results support previous literature regarding the upper body or postural adaptation and extend these findings to the realm of gait. Results highlight the PPC as a potential target for neurorehabilitation designed to improve gait adaptability., (Copyright © 2020 Young, Parikh and Layne.)

Comprehensive analysis of daily, online adaptive plan quality and safety in magnetic resonance imaging (MRI) guided radiation therapy is critical to its widespread use. Artificial neural network models developed with offline plans created after simulation were used to analyze and compare online plans that were adapted and reoptimized in real time prior to treatment. Roughly one third of 60 Co adapted plans were of inferior quality relative to fully optimized, offline plans, but MRI-linac adapted plans were essentially equivalent to offline plans. The models also enabled clear justification that MRI-linac plans are superior to 60 Co in an overwhelming majority of cases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Effective central sensory integration of visual, vestibular, and proprioceptive information is required to promote adaptability in response to changes in the environment during postural control. Patients with a lesion in the posterior parietal cortex (PPC) have an impaired ability to form an internal representation of body position, an important factor for postural control and adaptation. Suppression of PPC excitability has also been shown to decrease postural stability in some contexts. As of yet, it is unknown whether stimulation of the PPC may influence postural adaptation. This investigation aimed to identify whether transcranial direct current stimulation (tDCS) of the bilateral PPC could modulate postural adaptation in response to a bipedal incline postural adaptation task. Using young, healthy subjects, we delivered tDCS over bilateral PPC followed by bouts of inclined stance (incline-interventions). Analysis of postural after-effects identified differences between stimulation conditions for maximum lean after-effect (LAE; p = 0.005) as well as a significant interaction between condition and measurement period for the average position ( p = 0.03). We identified impaired postural adaptability following both active stimulation conditions. Results reinforce the notion that the PPC is involved in motor adaptation and extend this line of research to the realm of standing posture. The results further highlight the role of the bilateral PPC in utilizing sensory feedback to update one's internal representation of verticality and demonstrates the diffuse regions of the brain that are involved in postural control and adaptation. This information improves our understanding of the role of the cortex in postural control, highlighting the potential for the PPC as a target for sensorimotor rehabilitation., (Copyright © 2020 Young, Parikh and Layne.)

Dexterous object manipulation is a hallmark of human evolution and a critical skill for everyday activities. A previous work has used a grasping context that predominantly elicits memory-based control of digit forces by constraining where the object should be grasped. For this "constrained" grasping context, the primary motor cortex (M1) is involved in storage and retrieval of digit forces used in previous manipulations. In contrast, when choice of digit contact points is allowed ("unconstrained" grasping), behavioral studies revealed that forces are adjusted, on a trial-to-trial basis, as a function of digit position. This suggests a role of online feedback of digit position for force control. However, despite the ubiquitous nature of unconstrained hand-object interactions in activities of daily living, the underlying neural mechanisms are unknown. Using noninvasive brain stimulation, we found the role of primary motor cortex (M1) and somatosensory cortex (S1) to be sensitive to grasping context. In constrained grasping, M1 but not S1 is involved in storing and retrieving learned digit forces and position. In contrast, in unconstrained grasping, M1 and S1 are involved in modulating digit forces to position. Our findings suggest that the relative contribution of memory and online feedback modulates sensorimotor cortical interactions for dexterous manipulation., (© The Author(s) 2019. Published by Oxford University Press.)

Neuronal firing rate variability prior to movement onset contributes to trial-to-trial variability in primate behavior. However, in humans, whether similar mechanisms contribute to trial-to-trial behavioral variability remains unknown. We investigated the time-course of trial-to-trial variability in corticospinal excitability (CSE) using transcranial magnetic stimulation (TMS) during a self-paced reach-to-grasp task. We hypothesized that CSE variability will be modulated prior to the initiation of reach and that such a modulation would explain trial-to-trial behavioral variability. Able-bodied individuals were visually cued to plan their grip force before exertion of either 30% or 5% of their maximum pinch force capacity on an object. TMS was delivered at six time points (0.5, 0.75, 1, 1.1, 1.2, and 1.3 s) following a visual cue that instructed the force level. We first modeled the relation between CSE magnitude and its variability at rest ( n = 12) to study the component of CSE variability pertaining to the task but not related to changes in CSE magnitude ( n = 12). We found an increase in CSE variability from 1.2 to 1.3 s following the visual cue at 30% but not at 5% of force. This effect was temporally dissociated from the decrease in CSE magnitude that was observed from 0.5 to 0.75 s following the cue. Importantly, the increase in CSE variability explained at least ∼40% of inter-individual differences in trial-to-trial variability in time to peak force rate. These results were found to be repeatable across studies and robust to different analysis methods. Our findings suggest that the neural mechanisms underlying modulation in CSE variability and CSE magnitude are distinct. Notably, the extent of modulation in variability in corticospinal system prior to grasp within individuals may explain their trial-to-trial behavioral variability., (Copyright © 2019 Rao and Parikh.)

Background: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated., Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method., Results: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX., Conclusions: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Adaptive magnetic resonance imaging-guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation., Methods: We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high-dose (biologically effective dose [BED 10 ] >70) and standard-dose groups (BED 10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan-Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT., Results: Median follow-up was 17 months. High-dose patients (n = 24, 55%) had statistically significant improvement in 2-year OS (49% vs 30%, P = 0.03) and trended towards significance for 2-year FFLF (77% vs 57%, P = 0.15) compared to standard-dose patients (n = 20, 45%). FFDF at 18 months in high-dose vs standard-dose groups was 24% vs 48%, respectively (P = 0.92). High-dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21-0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72-0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard-dose group and did not occur in the high-dose group., Conclusions: Patients treated with dose-escalated MRgRT demonstrated improved OS. Prospective evaluation of high-dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Sensorimotor memory built through previous hand-object interactions allows subjects to plan grasp forces. The memory-based mechanism is particularly effective when contact points on the object do not change across multiple manipulations, thus allowing subjects to generate the same forces in a feedforward fashion. However, allowing subjects to choose where to grasp an object causes trial-to-trial variability in fingertip positioning, suggesting a decreased ability to predict where the object will be grasped. In this scenario, subjects modulate forces on a trial-to-trial basis as a function of fingertip positioning. We suggested that this fingertip force-to-position modulation could be implemented by transforming feedback of digit placement into an accurate distribution of fingertip forces. Thus, decreasing certainty of fingertip position on an object would cause a shift from predominantly memory- to feedback-based force control mechanisms. To gain further insight into these sensorimotor transformation mechanisms, we asked subjects to grasp and lift an object with an asymmetrical center of mass while preventing it from tilting. To isolate the effect of digit placement uncertainty, we designed two experimental conditions that differed in terms of predictability of fingertip position but had similar average fingertip positioning and force distribution. We measured corticospinal excitability to probe possible changes in sensorimotor processing associated with digit placement uncertainty. We found a differential effect of sensorimotor uncertainty after but not before object contact. Our results suggest that sensorimotor integration is rapidly tuned after object contact based on different processing demands for memory versus feedback mechanisms underlying the control of manipulative forces. NEW & NOTEWORTHY The relative contribution of predictive and feedback mechanisms for scaling digit forces to position during dexterous manipulation depends on the predictability of where the object will be grasped. We found that corticospinal excitability shortly after contact was sensitive to digit position predictability. This supports the proposition that distinct sensorimotor integration processes are engaged, depending on the role of feedback about digit placement versus sensorimotor memory in controlling manipulative forces.

Background: The prognosis of patients with hepatic metastases from neuroendocrine tumors (NET) is generally good, and radioembolization with Yttrium-90 microspheres is a locoregional therapy that is used in efforts to improve hepatic disease control and survival. This study aims to describe the survival outcomes and toxicities associated with radioembolization for hepatic-predominant metastatic NET in a large single-institution cohort., Methods: A total of 59 patients underwent radioembolization for metastatic NET with hepatic predominant disease at a single academic center. Patient outcomes were analyzed by Kaplan-Meier survival analysis and toxicities were detailed and described. Ten patients within the cohort underwent post-treatment dosimetric analysis using PET-MRI and normal liver dosimetry was correlated with hepatic fibrosis and toxicity., Results: Median overall survival from time of radioembolization in the patient cohort was 31 months, and the 1- and 2-year overall survival was 80.4% and 65.6% respectively. Median hepatic progression-free survival and overall progression-free survival were 18 and 13 months, respectively. Three patients died of hepatic failure that was possibly therapy-related. Ten patients underwent evaluation of post-treatment dosimetry following radioembolization. In patients who did not develop hepatotoxicity or hepatic fibrosis, mean dose to normal liver was 25.4 Gy, while the mean liver dose in patients who experienced toxicity (hepatic fibrosis in n=2 and death from hepatic failure in n=1) was 59.1 Gy., Conclusions: Overall survival following radioembolization for hepatic metastases from NET is excellent; however, deaths that are potentially treatment-related have been observed. Preliminary data regarding dose to normal liver is suggestive of a relation between dosimetry and toxicity, however further work is required to further elucidate the mechanism, correlation with dosimetry, as well as additional patient and tumor factors that may predispose these patients to toxicity., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial., Methods and Materials: Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded., Results: All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified., Conclusions: SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.

Objectives: To develop an early warning discharge disposition prediction tool based on clinical and health services factors for hospitalized patients. Recent study results suggest that early prediction of discharge disposition (ie, whether patients can return home or require placement in a facility) can improve care coordination, expedite care planning, and reduce length of stay., Study Design: Retrospective analysis of inpatient data; development of multiple logistic regression model and an easy-to-use score., Methods: We used retrospective data from all patients who were admitted in 2013 to the general medical service at the Veterans Affairs Boston Healthcare System and discharged alive. A derivation-validation approach was used to build a multiple logistic regression model, which was transformed into a score for potential implementation., Results: Of the 4760 patients discharged in 2013, 485 (10.2%) were discharged to a facility other than home. Correlates of discharge to a facility included a primary admission diagnosis of neoplasm (odds ratio [OR], 2.71; 95% CI, 1.73-4.25), diseases of the nervous system (OR, 2.53; 95% CI, 1.26-5.08), and musculoskeletal diseases (OR, 2.55; 95% CI, 1.52-4.27), as well as discharge to a facility during previous hospitalization. Patients with a prior primary diagnosis of circulatory disorder and those with comorbidity of hypertension, either complicated or uncomplicated, were less likely to be discharged to a facility. A value of 5 or greater on the 20-point scale indicated discharge to a facility with 83% sensitivity and 48% specificity., Conclusions: A validated, easy-to-use score can assist providers in identifying upon admission those patients who may not be able to go directly home after hospitalization, thus facilitating early discharge planning and coordination, potentially reducing length of hospital stay and improving patient experience.

Purpose: Daily magnetic resonance (MR)-guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment., Methods and Materials: Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ 2 test., Results: The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively., Conclusions: This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

Background: Yttrium-90 ( 90 Y) radioembolization involves the intra-arterial delivery of radioactive microspheres to treat hepatic malignancies. Though this therapy involves careful pre-treatment planning and imaging, little is known about the precise location of the microspheres once they are administered. Recently, there has been growing interest post-radioembolization imaging using positron-emission tomography (PET) for quantitative dosimetry and identifying lesions that may benefit from additional salvage therapy. In this study, we aim to measure the inter-center variability of 90 Y PET measurements as measured on PET/MRI in preparation for a multi-institutional prospective phase I/II clinical trial. Eight institutions participated in this study and followed a standardized phantom filling and imaging protocol. The NEMA NU2-2012 body phantom was filled with 3 GBq of 90 Y chloride solution. The phantom was imaged for 30 min in listmode on a Siemens Biograph mMR non-TOF PET/MRI scanner at five time points across 10 days (0.3-3.0 GBq). Raw PET data were sent to a central site for image reconstruction and data analysis. Images were reconstructed with optimal parameters determined from a previous study. Volumes of interest (VOIs) matching the known sphere diameters were drawn on the vendor-provided attenuation map and propagated to the PET images. Recovery coefficients (RCs) and coefficient of variation of the RCs (COV) were calculated from these VOIs for each sphere size and activity level., Results: Mean RCs ranged from 14.5 to 75.4%, with the lowest mean RC coming from the smallest sphere (10 mm) on the last day of imaging (0.16 MBq/ml) and the highest mean RC coming from the largest sphere (37 mm) on the first day of imaging (2.16 MBq/ml). The smaller spheres tended to exhibit higher COVs. In contrast, the larger spheres tended to exhibit lower COVs. COVs from the 37 mm sphere were < 25.3% in all scans. For scans with ≥ 0.60 MBq/ml, COVs were ≤ 25% in spheres ≥ 22 mm. However, for all other spheres sizes and activity levels, COVs were usually > 25%., Conclusions: Post-radioembolization dosimetry of lesions or other VOIs ≥ 22 mm in diameter can be consistently obtained (< 25% variability) at a multi-institutional level using PET/MRI for any clinically significant activity for 90 Y radioembolization.

Background: To simplify the adaptive treatment planning workflow while achieving the optimal tumor-dose coverage in pancreatic cancer patients undergoing daily adaptive magnetic resonance image guided radiation therapy (MR-IGRT)., Methods: In daily adaptive MR-IGRT, the plan objective function constructed during simulation is used for plan re-optimization throughout the course of treatment. In this study, we have constructed the initial objective functions using two methods for 16 pancreatic cancer patients treated with the ViewRay™ MR-IGRT system: 1) the conventional method that handles the stomach, duodenum, small bowel, and large bowel as separate organs at risk (OARs) and 2) the OAR grouping method. Using OAR grouping, a combined OAR structure that encompasses the portions of these four primary OARs within 3 cm of the planning target volume (PTV) is created. OAR grouping simulation plans were optimized such that the target coverage was comparable to the clinical simulation plan constructed in the conventional manner. In both cases, the initial objective function was then applied to each successive treatment fraction and the plan was re-optimized based on the patient's daily anatomy. OAR grouping plans were compared to conventional plans at each fraction in terms of coverage of the PTV and the optimized PTV (PTV OPT), which is the result of the subtraction of overlapping OAR volumes with an additional margin from the PTV., Results: Plan performance was enhanced across a majority of fractions using OAR grouping. The percentage of the volume of the PTV covered by 95% of the prescribed dose (D 95 ) was improved by an average of 3.87 ± 4.29% while D 95 coverage of the PTV OPT increased by 3.98 ± 4.97%. Finally, D 100 coverage of the PTV demonstrated an average increase of 6.47 ± 7.16% and a maximum improvement of 20.19%., Conclusions: In this study, our proposed OAR grouping plans generally outperformed conventional plans, especially when the conventional simulation plan favored or disregarded an OAR through the assignment of distinct weighting parameters relative to the other critical structures. OAR grouping simplifies the MR-IGRT adaptive treatment planning workflow at simulation while demonstrating improved coverage compared to delivered pancreatic cancer treatment plans in daily adaptive radiation therapy.

For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 (OR 0.73), female gender (OR 0.81), Charlson-Deyo comorbidity score ≥2 (OR 0.82), and high-volume centers (OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 (OR 0.79) and Clinical Stage III (OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology (OR 1.33) and nonacademic cancer centers (OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 (OR 0.15), female gender (OR 0.80), and non-Caucasian race (OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology (OR 2.10) and high-volume centers (OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49) to trimodality therapy (HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Electronic Consultation (e-consults) can provide improved access, enhance patient and provider satisfaction, and reduce beneficiary travel expenses. We explored how e-consults were implemented across three specialty areas, diabetes (Diab), gastroenterology (GI), and neurosurgery (Neuro), at two Veterans Affairs hospitals in terms of strategies for use and time-lines., Methods: We conducted observations and electronically shadowed patient e-consultations submitted to a specialty care service by primary care provider(s) at the two sites during a thirteen-month period. We divided the e-consult process in each specialty into three broad milestones; Request (from primary to specialty), Response (from specialty back to primary), and Follow up (from primary to patient), and recorded the flow and time in each category. An overall hierarchy of e-consults was developed to illustrate the many ways an e-consult was used. The Kolmogorov-Smirnov test was used to compare the distribution of time across specialties., Results: A total of 394 consults submitted between April 14, 2012 and May 2, 2013 were reviewed (Diab=152, GI=169, Neuro=73). Of the 152 diabetes specialty clinic e-consults, 35% required some sort of direct contact with the patient by the specialty clinic before a recommendation was provided. Overall, 58% of the e-consults were completed within 20days, while 68% were completed within 30days. The Response times between Diab and GI were significantly different (median=0 vs. 3days; p<0.0001) and so were Follow up times (median=0 vs. 4days; p<0.0001). All three stages were statistically different between Diab and Neuro; however, there was not enough evidence to suggest any differences between GI and Neuro., Conclusions: The use of an e-consult is likely to vary based on the specialty, but the often significant variations in time may continue to hinder prompt access to care. E-consult design, implementation, documentation, training, self-learning, and monitoring should be tailored to get the most benefit out of this system., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: 18 F-fluorodeoxyglucose (FDG) positron emission tomography-(PET)/computed tomography (CT) imaging is used for staging and treatment planning of patients with anal cancer. Quantitative pre- and posttreatment metrics that are predictive of recurrence are unknown. We evaluated the association between pre- and posttreatment FDG-PET/CT parameters and outcomes for patients with squamous cell carcinoma of the anus (SCCA)., Methods and Materials: The records of 110 patients treated between 2003 and 2013 with definitive radiation therapy for SCCA were reviewed under an institutional review board-approved protocol. The median radiation therapy dose was 50.4 Gy (range, 35-60 Gy). Concurrent chemotherapy was administered for 109 of 110 patients and generally consisted of 5-fluorouracil and mitomycin C (n = 94). All patients underwent pretreatment FDG-PET/CT and 101 of 110 underwent posttreatment FDG-PET/CT 3 months after completion of radiation therapy. The maximum standard uptake value (SUV max ) was analyzed, in addition to multiple patient and treatment factors, by univariate and multivariate Cox regression for correlation with local recurrence (LR) and overall survival (OS)., Results: The median follow-up was 28.6 months. LR occurred in 1 of 15 (6.7%), 5 of 47 (10.6%), and 6 of 48 (12.5%) patients with stage I, II, and III disease, respectively. On univariate analysis, a significant association was observed between reduced LR and posttreatment SUV max <6.1 ( P = .0095) and between increased OS and posttreatment SUV max <6.1 ( P = .0086). On multivariate analysis, a significant association was observed between reduced LR and posttreatment SUV max <6.1 ( P = .0013) and the use of intensity modulated radiation therapy ( P < .001). A significant multivariate association was observed between increased OS and posttreatment SUV max <6.1 ( P = .0373) and the use of 5-fluorouracil/mitomycin C chemotherapy ( P = .001)., Conclusion: Posttreatment SUV max <6.1 is associated with reduced LR and increased OS after chemoradiation therapy for SCCA independent of T and N stage on multivariate analysis. Greater follow-up is required to confirm this association with late patterns of failure.

Background & Objectives: Multidisciplinary tumor boards (MDTBs) are frequently employed in cancer centers but their value has been debated. We reviewed the decision-making process and resource utilization of our MDTB to assess its utility in the management of pancreatic and upper gastrointestinal tract conditions., Methods: A prospectively-collected database was reviewed over a 12-month period. The primary outcome was change in management plan as a result of case discussion. Secondary outcomes included resources required to hold MDTB, survival, and adherence to treatment guidelines., Results: Four hundred seventy cases were reviewed. MDTB resulted in a change in the proposed plan of management in 101 of 402 evaluable cases (25.1%). New plans favored obtaining additional diagnostic workup. No recorded variables were associated with a change in plan. For newly-diagnosed cases of pancreatic ductal adenocarcinoma (n = 33), survival time was not impacted by MDTB (p = .154) and adherence to National Comprehensive Cancer Network guidelines was 100%. The estimated cost of physician time per case reviewed was $190., Conclusions: Our MDTB influences treatment decisions in a sizeable number of cases with excellent adherence to national guidelines. However, this requires significant time expenditure and may not impact outcomes. Regular assessments of the effectiveness of MDTBs should be undertaken., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Conditional learning is an important component of our everyday activities (e.g., handling a phone or sorting work files) and requires identification of the arbitrary stimulus, accurate selection of the motor response, monitoring of the response, and storing in memory of the stimulus-response association for future recall. Learning this type of conditional visuomotor task appears to engage the premotor dorsal region (PMd). However, the extent to which PMd might be involved in specific or all processes of conditional learning is not well understood. Using transcranial magnetic stimulation (TMS), we demonstrate the role of human PMd in specific stages of learning of a novel conditional visuomotor task that required subjects to identify object center of mass using a color cue and to apply appropriate torque on the object at lift onset to minimize tilt. TMS over PMd, but not vertex, increased error in torque exerted on the object during the learning trials. Analyses of digit position and forces further revealed that the slowing in conditional visuomotor learning resulted from impaired monitoring of the object orientation during lift, rather than stimulus identification, thus compromising the ability to accurately reduce performance error across trials. Importantly, TMS over PMd did not alter production of torque based on the recall of learned color-torque associations. We conclude that the role of PMd for conditional learning is highly sensitive to the stage of learning visuomotor associations., New & Noteworthy: Conditional learning involves stimulus identification, motor response selection, response monitoring, memory encoding, and recall of the learned association. Premotor dorsal (PMd) has been implicated for conditional learning. However, the extent to which PMd might be involved in specific or all stages of conditional learning is not well understood. The novel finding of our study is that PMd appears to be involved with monitoring motor responses, a sensorimotor integration stage essential for conditional learning., (Copyright © 2017 the American Physiological Society.)

On-board magnetic resonance (MR) image guidance during radiation therapy offers the potential for more accurate treatment delivery. To utilize the real-time image information, a crucial prerequisite is the ability to successfully segment and track regions of interest (ROI). The purpose of this work is to evaluate the performance of different segmentation algorithms using motion images (4 frames per second) acquired using a MR image-guided radiotherapy (MR-IGRT) system. Manual con-tours of the kidney, bladder, duodenum, and a liver tumor by an experienced radiation oncologist were used as the ground truth for performance evaluation. Besides the manual segmentation, images were automatically segmented using thresholding, fuzzy k-means (FKM), k-harmonic means (KHM), and reaction-diffusion level set evolution (RD-LSE) algorithms, as well as the tissue tracking algorithm provided by the ViewRay treatment planning and delivery system (VR-TPDS). The performance of the five algorithms was evaluated quantitatively by comparing with the manual segmentation using the Dice coefficient and target registration error (TRE) measured as the distance between the centroid of the manual ROI and the centroid of the automatically segmented ROI. All methods were able to successfully segment the bladder and the kidney, but only FKM, KHM, and VR-TPDS were able to segment the liver tumor and the duodenum. The performance of the thresholding, FKM, KHM, and RD-LSE algorithms degraded as the local image contrast decreased, whereas the performance of the VP-TPDS method was nearly independent of local image contrast due to the reference registration algorithm. For segmenting high-contrast images (i.e., kidney), the thresholding method provided the best speed (< 1 ms) with a satisfying accuracy (Dice = 0.95). When the image contrast was low, the VR-TPDS method had the best automatic contour. Results suggest an image quality determination procedure before segmentation and a combination of different methods for optimal segmentation with the on-board MR-IGRT system.

Purpose: Locally recurrent rectal cancer may cause significant morbidity. Prior reports of rectal cancer reirradiation following local recurrence suggest treatment efficacy, with variable rates of late toxicity. Modern techniques including intensity modulated radiation therapy (IMRT) may improve the therapeutic index. We report outcomes for pelvic reirradiation as treatment for rectal cancer using IMRT., Methods and Materials: The records of 31 patients undergoing reirradiation for rectal cancer between 2004 and 2013 were reviewed. All patients underwent IMRT using an accelerated hyperfractionation (39 Gy in 1.5-Gy fractions delivered twice daily, n=15) or once-daily fractionation technique (median dose, 30.4 Gy; range, 27-40 Gy in 15-22 fractions; n = 16). The median cumulative dose was 77 Gy (range, 59-113), and the median interval from prior pelvic radiation therapy was 39.8 months (range, 10.1-307.6). Treatment intent was palliative in 20 patients and neoadjuvant or adjuvant in 11 patients. Surgery was generally reserved for patients with an isolated local recurrence. Concurrent chemotherapy was administered for 25/31 patients, most frequently capecitabine (n=11) or continuous infusion 5-fluorouracil (n=10)., Results: Median follow-up was 11.3 months. The prescribed treatment was completed in 29/31 patients (93.5%). Among 18 patients with symptoms attributable to recurrent disease, successful palliation was achieved in 10/18 (55.6%). The rate of grade 2 and grade 3 acute toxicities was 32.3% and 3.2%, respectively. Local control rates at 1 and 2 years were 61.3% and 47.3%, respectively. Median overall survival was 21.9 months, and 1-year survival was 66.7% for patients who had surgical resection versus 58.7% for those who did not ( P = .0802)., Conclusions: Rectal cancer reirradiation using IMRT is well-tolerated in the setting of prior pelvic radiation therapy. Given significant risk of local progression, further dose escalation may be warranted for patients with life expectancy exceeding 1 year.

The contribution of poor finger force control to age-related decline in manual dexterity is above and beyond ubiquitous behavioral slowing. Altered control of the finger forces can impart unwanted torque on the object affecting its orientation, thus impairing manual performance. Anodal transcranial direct current stimulation (tDCS) over primary motor cortex (M1) has been shown to improve the performance speed on manual tasks in older adults. However, the effects of anodal tDCS over M1 on the finger force control during object manipulation in older adults remain to be fully explored. Here we determined the effects of anodal tDCS over M1 on the control of grip force in older adults while they manipulated an object with an uncertain mechanical property. Eight healthy older adults were instructed to grip and lift an object whose contact surfaces were unexpectedly made more or less slippery across trials using acetate and sandpaper surfaces, respectively. Subjects performed this task before and after receiving anodal or sham tDCS over M1 on two separate sessions using a cross-over design. We found that older adults used significantly lower grip force following anodal tDCS compared to sham tDCS. Friction measured at the finger-object interface remained invariant after anodal and sham tDCS. These findings suggest that anodal tDCS over M1 improved the control of grip force during object manipulation in healthy older adults. Although the cortical networks for representing objects and manipulative actions are complex, the reduction in grip force following anodal tDCS over M1 might be due to a cortical excitation yielding improved processing of object-specific sensory information and its integration with the motor commands for production of manipulative forces. Our findings indicate that tDCS has a potential to improve the control of finger force during dexterous manipulation in older adults.

Abstract Transcranial anodal stimulation (tDCS) over primary motor cortex (M1) improves dexterous manipulation in healthy older adults. However, the beneficial effects of anodal tDCS in combination with motor practice on natural and clinically relevant functional manual tasks, and the associated changes in the digit contact forces are not known. To this end, we studied the effects of 20 min of tDCS applied over M1 for the dominant hand combined with motor practice (MP) in a sham-controlled crossover study. We monitored the forces applied to an object that healthy elderly individuals grasped and manipulated, and their performances on the Grooved Pegboard Test and the Key-slot task. Practice improved performance on the Pegboard test, and anodal tDCS + MP improved retention of this performance gain when tested 35 min later, whereas similar performance gains degraded in the sham group after 35 min. Interestingly, grip force variability on an isometric precision grip task performed with visual feedback of precision force increased following anodal tDCS + MP, but not sham tDCS + MP. This finding suggests that anodal tDCS over M1 might alter the descending drive to spinal motor neurons involved in the performance of isometric precision grip task under visual feedback leading to increased fluctuations in the grip force exerted on the object. Our results demonstrate that anodal stimulation in combination with motor practice helps older adults to retain their improved performance on a functionally relevant manual task in healthy older adults.

Behavior-based ergonomics therapy (BBET) has been proposed in the past as a viable individualized non-pharmacological intervention to manage challenging behaviors and promote engagement among long-term care residents diagnosed with Alzheimer's/dementia. We evaluate the effect of BBET on quality of life and behavioral medication usage in an 18-bed dementia care unit at a not-for-profit continuing care retirement community in West Central Ohio. Comparing a target cohort during the 6-month pre-implementation period with the 6-month post-implementation period, our study indicates that BBET appears to have a positive impact on the resident's quality of life and also appears to correlate with behavioral medical reduction. For instance, the number of days with behavioral episodes decreased by 53%, the total Minimum Data Set (MDS) mood counts decreased by 70%, and the total MDS behavior counts decreased by 65%. From a medication usage standpoint, the number of pro re nata (PRN) Ativan doses decreased by 57%.

Person-centered, nonpharmacological interventions for managing Alzheimer's/dementia-related behavioral disturbances have received significant attention. However, such interventions are quite often of a single type limiting their benefits. We develop a comprehensive nonpharmacological intervention, the Behavior-Based Ergonomic Therapy (BBET), which consists of multiple therapies. This low-cost, 24/7 program uses learning, personality, and behavioral profiles and cognitive function of each resident to develop a set of individualized therapies. These therapies are made available through an accessible resource library of music and video items, games and puzzles, and memory props to provide comfort or stimulation depending on an individual resident's assessment. The quantitative and qualitative benefits of the BBET were evaluated at the dementia care unit in a not-for-profit continuing care retirement community in west central Ohio. The 6-month pilot study reduced falls by 32.5% and markedly reduced agitation through increased resident engagement.

We measured the external moments and digit-tip force directions acting on a freely moveable object while it was grasped and manipulated by old (OA) and young (YA) adults. Participants performed a grasp and lift task and a precision orientation (key-slot) task with a precision (thumb-finger) grip. During the grasp-lift task the OA group misaligned their thumb and finger contacts and produced greater grip force, greater external moments on the object around its roll axis, and oriented force vectors differently compared with the YA group. During the key-slot task, the OA group was more variable in digit-tip force directions and performed the key-slot task more slowly. With practice the OA group aligned their digits, reduced their grip force, and minimized external moments on the object, clearly demonstrating that the nervous system monitored and actively manipulated one or more variables related to object tilt. This was true even for the grip-lift task, a task for which no instructions regarding object orientation were given and which could tolerate modest amounts of object tilt without interfering with task goals. Although the OA group performed the key-slot task faster with experience, they remained slower than the YA group. We conclude that with old age comes a reduced ability to control the forces and moments applied to objects during precision grasp and manipulation. This may contribute to the ubiquitous slowing and deteriorating manual dexterity in healthy aging.

Purpose: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy., Patients and Methods: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas., Results: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%., Conclusion: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel.