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Abstract Background Body weight support systems with three or more degrees of freedom (3-DoF) are permissive and safe environments that provide unloading and allow unrestricted movement in any direction. This enables training of walking and balance control at an early stage in rehabilitation. Transparent systems generate a support force vector that is near vertical at all positions in the workspace to only minimally interfere with natural movement patterns. Patients with impaired balance, however, may benefit from additional mediolateral support that can be adjusted according to their capacity. An elegant solution for providing balance support might be by rendering viscous damping along the mediolateral axis via the software controller. Before use with patients, we evaluated if control-rendered mediolateral damping evokes the desired stability enhancement in able-bodied individuals. Methods A transparent, cable-driven robotic body weight support system (FLOAT) was used to provide transparent body weight support with and without mediolateral damping to 21 able-bodied volunteers while walking at preferred gait velocity on a treadmill. Stability metrics reflecting resistance to small and large perturbations were derived from walking kinematics and compared between conditions and to free walking. Results Compared to free walking, the application of body weight support per-se resulted in gait alterations typically associated with body weight support, namely increased step length and swing phase. Frontal plane dynamic stability, measured by kinematic variability and nonlinear dynamics of the center of mass, was increased under body weight support, indicating reduced balance requirements in both damped and undamped support conditions. Adding damping to the body weight support resulted in a greater increase of frontal plane stability. Conclusion Adding mediolateral damping to 3-DoF body weight support systems is an effective method of increasing frontal plane stability during walking in able-bodied participants. Building on these results, adjustable mediolateral damping could enable therapists to select combinations of unloading and stability specifically for each patient and to adapt this in a task specific manner. This could extend the impact of transparent 3-DoF body weight support systems, enabling training of gait and active balance from an early time point onwards in the rehabilitation process for a wide range of mobility activities of daily life.

Abstract Background After a neurological injury, mobility focused rehabilitation programs intensively train walking on treadmills or overground. However, after discharge, quite a few patients are not able to independently negotiate stairs, a real-world task with high physical and psychological demands and a high injury risk. To decrease fall risk and improve patients’ capacity to navigate typical environments, early stair negotiation training can help restore competence and confidence in safe stair negotiation. One way to enable early training in a safe and permissive environment is to unload the patient with a body weight support system. We here investigated if unloaded stair negotiation complies with basic locomotor principles, in terms of enabling performance of a physiological movement pattern with minimal compensation. Methods Seventeen able-bodied participants were unloaded with 0–50% bodyweight during self-paced ascent and descent of a 4-tread staircase. Spatio-temporal parameters, joint ranges of motion, ground reaction forces and myoelectric activity in the main lower limb muscles of participants were compared between unloading levels. Likelihood ratio tests of separated linear mixed models of the investigated outcomes assessed if unloading affects the parameters in general. Subsequent post-hoc testing revealed which levels of unloading differed from unsupported stair negotiation. Results Unloading affected walking velocity, joint ranges of motion, vertical ground reaction force parameters and myoelectric activity in all investigated muscles for stair ascent and descent while step width and single support duration were only affected during ascent. A reduction with increasing levels of body weight support was seen in walking velocity (0.07–0.12 m/s), ranges of motion of the knee and hip (2–10°), vertical ground reaction force peaks (10–70%) and myoelectric activity (17–70%). An increase with unloading was only seen during ascent for ankle range of motion and tibialis anterior activity at substantial unloading. Conclusions Body weight support facilitates stair negotiation by providing safety and support against gravity. Although unloading effects are present in most parameters, up to 30% body weight support these changes are small, and no dysfunctional patterns are introduced. Body weight support therefore fulfills all the necessary requirements for early stair negotiation training.

Abstract Background Body weight supported locomotor training was shown to improve walking function in neurological patients and is often performed on a treadmill. However, walking on a treadmill does not mimic natural walking for several reasons: absent self-initiation, less active retraction of leg required and altered afferent input. The superiority of overground training has been suggested in humans and was shown in rats demonstrating greater plasticity especially in descending pathways compared to treadmill training. We therefore developed a body weight support system allowing unrestricted overground walking with minimal interfering forces to train neurological patients. The present study investigated the influence of different amounts of body weight support on gait in healthy individuals. Methods Kinematic and electromyographic data of 19 healthy individuals were recorded during overground walking at different levels of body weight support (0, 10, 20, 30, 40, and 50%). Upper body inclination, lower body joint angles and multi-joint coordination as well as time-distance parameters were calculated. Continuous data were analyzed with regard to distinct changes within a gait cycle across all unloading conditions. Results Temporal gait parameters were most sensitive to changes in body unloading while spatial variables (step length, joint angles) showed modest responses when unloaded by as much as 50% body weight. The activation of the gastrocnemius muscle showed a gradual decrease with increasing unloading while the biceps femoris muscle showed increased activity levels at 50% unloading. These changes occurred during stance phase while swing phase activity remained unaltered. Conclusions Healthy individuals were able to keep their walking kinematics strikingly constant even when unloaded by half of their body weight, suggesting that the weight support system permits a physiological gait pattern. However, maintaining a given walking speed using close-to-normal kinematics while being unloaded was achieved by adapting muscle activity patterns. Interestingly, the required propulsion to maintain speed was not achieved by means of increased gastrocnemius activity at push-off, but rather through elevated biceps femoris activity while retracting the leg during stance phase. It remains to be investigated to what extent neurological patients with gait disorders are able to adapt their gait pattern in response to body unloading.

On 16–17 November 2000, a relatively intense precipitation event on the north-western Italy was heavily underestimated, mainly due to shifting error, by three operational 10-km limited area models (LAMs) which differ about basic equations, domain size, and parameterisation schemes. The scope of the work is to investigate possible common error-sources independent from the single model, in particular the effect of initialisation. Thus, the complex evolution over the western Mediterranean Sea of the cyclone responsible for the event was investigated. Several objective and subjective verification techniques have been employed to check one of the LAMs' forecast against the available observations (precipitation from rain gauge and retrieved from ground-based radar, and satellite-retrieved atmospheric humidity patterns). Despite a clear statement is not achieved, results indicate that high sensitivity to the initial conditions, and the inadequacy of the observational network on the southern Mediterranean area, can play a major role in producing the forecast shifting error on the target area.

Spinal Cord Injury (SCI) presents a significant challenge in rehabilitation medicine, with recovery outcomes varying widely among individuals. Machine learning (ML) is a promising approach to enhance the prediction of recovery trajectories, but its integration into clinical practice requires a thorough understanding of its efficacy and applicability. We systematically reviewed the current literature on data-driven models of SCI recovery prediction. The included studies were evaluated based on a range of criteria assessing the approach, implementation, input data preferences, and the clinical outcomes aimed to forecast. We observe a tendency to utilize routinely acquired data, such as International Standards for Neurological Classification of SCI (ISNCSCI), imaging, and demographics, for the prediction of functional outcomes derived from the Spinal Cord Independence Measure (SCIM) III and Functional Independence Measure (FIM) scores with a focus on motor ability. Although there has been an increasing interest in data-driven studies over time, traditional machine learning architectures, such as linear regression and tree-based approaches, remained the overwhelmingly popular choices for implementation. This implies ample opportunities for exploring architectures addressing the challenges of predicting SCI recovery, including techniques for learning from limited longitudinal data, improving generalizability, and enhancing reproducibility. We conclude with a perspective, highlighting possible future directions for data-driven SCI recovery prediction and drawing parallels to other application fields in terms of diverse data types (imaging, tabular, sequential, multimodal), data challenges (limited, missing, longitudinal data), and algorithmic needs (causal inference, robustness)., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Oncoplastic surgery has become an important part of the surgical repertoire to offer both oncologically safe and aesthetically pleasing results in patients with breast cancer. Data comparing oncoplastic and reconstructive breast surgeries are limited. This study aimed to assess patient-reported outcomes (PRO) in our cohort of oncoplastic and reconstructively operated patients., Methods: Patients who underwent oncoplastic surgery, including immediate reconstruction by a single surgeon, between 2010 and 2018 were contacted to participate in this study. In total, 157 patients fulfilled the inclusion criteria. 54 patient data sets were used for statistical evaluation. Body Image Scale (BIS) and BreastQ questionnaires were used to measure subjective PRO scores, and pictures were taken to objectively measure symmetry using the Breast Analyzing Tool (BAT). Patients were divided into three groups according to the Tübingen classification (group 1: Tübingen 3-4 ( n = 16), group 2: Tübingen 5 ( n = 26), group 3: Breast Reconstruction/Tübingen 6 ( n = 12])., Results: The mean age was 53.5 for group 1, 51.4 for group 2 and 46.8 for group 3. The mean follow-up was 62.9 ± 35.82 months. BIS was significantly better in group 3 (3.92 ± 1.73) than in group 1 and 2 (7.69 ± 4.48 and 4.81 ± 3.41, p = 0.016). Symmetry measured using BAT showed only a trend favoring reconstruction ( p = 0.12). The BreastQ item "Sexual well-being" was significantly better in oncoplastic breast reduction surgery ( p = 0.036)., Conclusion: BIS was better after reconstructive breast surgery than after oncoplastic surgery. Reconstructive breast surgery in experienced breast care units offers high patient satisfaction and a high quality of life., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Abrupt radiocarbon ( 14 C) excursions, or Miyake events, in sequences of radiocarbon measurements from calendar-dated tree-rings provide opportunities to assign absolute calendar dates to undated wood samples from contexts across history and prehistory. Here, we report a tree-ring and 14 C-dating study of the Neolithic site of Dispilio, Northern Greece, a waterlogged archaeological site on Lake Kastoria. Findings secure an absolute, calendar-dated time using the 5259 BC Miyake event, with the final ring of the 303-year-long juniper tree-ring chronology dating to 5140 BC. While other sites have been absolutely dated to a calendar year through 14 C-signature Miyake events, Dispilio is the first European Neolithic site of these and it provides a fixed, calendar-year anchor point for regional chronologies of the Neolithic., (© 2024. The Author(s).)

Throughout history, humans have relied on wood for constructions, tool production or as an energy source. How and to what extent these human activities have impacted plant abundance and composition over a long-term perspective is, however, not well known. To address this knowledge gap, we combined 44,239 precisely dated tree-ring samples from economically and ecologically important tree species (spruce, fir, pine, oak) from historical buildings, and pollen-based plant cover estimates using the REVEALS model from 169 records for a total of 34 1° × 1° grid cells for Central Europe. Building activity and REVEALS estimates were compared for the entire study region (4-15°E, 46-51°N), and for low (<500 m asl) and mid/high elevations (≥500 m asl) in 100-year time windows over the period 1150-1850. Spruce and oak were more widely used in wooden constructions, amounting to 35 % and 32 %, respectively, compared to pine and fir. Besides wood properties and species abundance, tree diameters of harvested individuals, being similar for all four species, were found to be the most crucial criterion for timber selection throughout the last millennium. Regarding land use changes, from the 1150-1250's onwards, forest cover generally decreased due to deforestation until 1850, especially at lower elevations, resulting in a more heterogeneous landscape. The period 1650-1750 marks a distinct change in the environmental history of Central Europe; increasing agriculture and intense forest management practices were introduced to meet the high demands of an increasing population and intensifying industrialization, causing a decrease in palynological diversity, especially at low elevations. Likely the characteristic vegetation structure and composition of contemporary landscapes originated from that period. We further show that land use has impacted vegetation composition and diversity at an increasing speed leading to a general homogenization of landscapes through time, highlighting the limited environmental benefits of even-aged plantation forestry., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Most established clinical walking tests assess specific aspects of movement function (velocity, endurance, etc.) but are generally unable to determine specific biomechanical or neurological deficits that limit an individual's ability to walk. Recently, inertial measurement units (IMU) have been used to collect objective kinematic data for gait analysis and could be a valuable extension for clinical assessments (e.g., functional walking measures). This study assesses the reliability of an IMU-based overground gait analysis during the 2-min walk test (2mWT) in individuals with spinal cord injury (SCI). Furthermore, the study elaborates on the capability of IMUs to distinguish between different gait characteristics in individuals with SCI. Twenty-six individuals (aged 22-79) with acute or chronic SCI (AIS: C and D) completed the 2mWT with IMUs attached above each ankle on 2 test days, separated by 1 to 7 days. The IMU-based gait analysis showed good to excellent test-retest reliability (ICC: 0.77-0.99) for all gait parameters. Gait profiles remained stable between two measurements. Sensor-based gait profiling was able to reveal patient-specific gait impairments even in individuals with the same walking performance in the 2mWT. IMUs are a valuable add-on to clinical gait assessments and deliver reliable information on detailed gait pathologies in individuals with SCI.Trial registration: NCT04555759., (© 2024. The Author(s).)

Background: Walking impairments are a common consequence of neurological disorders and are assessed with clinical scores that suffer from several limitations. Robot-assisted locomotor training is becoming an established clinical practice. Besides training, these devices could be used for assessing walking ability in a controlled environment. Here, we propose an adaptive assist-as-needed (AAN) control for a treadmill-based robotic exoskeleton, the Lokomat, that reduces the support of the device (body weight support and impedance of the robotic joints) based on the ability of the patient to follow a gait pattern displayed on screen. We hypothesize that the converged values of robotic support provide valid and reliable information about individuals' walking ability., Methods: Fifteen participants with spinal cord injury and twelve controls used the AAN software in the Lokomat twice within a week and were assessed using clinical scores (10MWT, TUG). We used a regression method to identify the robotic measure that could provide the most relevant information about walking ability and determined the test-retest reliability. We also checked whether this result could be extrapolated to non-ambulatory and to unimpaired subjects., Results: The AAN controller could be used in patients with different injury severity levels. A linear model based on one variable (robotic knee stiffness at terminal swing) could explain 74% of the variance in the 10MWT and 61% in the TUG in ambulatory patients and showed good relative reliability but poor absolute reliability. Adding the variable 'maximum hip flexor torque' to the model increased the explained variance above 85%. This did not extend to non-ambulatory nor to able-bodied individuals, where variables related to stance phase and to push-off phase seem more relevant., Conclusions: The novel AAN software for the Lokomat can be used to quantify the support required by a patient while performing robotic gait training. The adaptive software might enable more challenging training conditions tuned to the ability of the individuals. While the current implementation is not ready for assessment in clinical practice, we could demonstrate that this approach is safe, and it could be integrated as assist-as-needed training, rather than as assessment., Trial Registration: ClinicalTrials.gov Identifier: NCT02425332., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Accurate prediction of walking function after a traumatic spinal cord injury (SCI) is crucial for an appropriate tailoring and application of therapeutical interventions. Long-term outcome of ambulation is strongly related to residual muscle function acutely after injury and its recovery potential. The identification of the underlying determinants of ambulation, however, remains a challenging task in SCI, a neurological disorder presented with heterogeneous clinical manifestations and recovery trajectories., Objectives: Stratification of walking function and determination of its most relevant underlying muscle functions based on stratified homogeneous patient subgroups., Methods: Data from individuals with paraplegic SCI were used to develop a prediction-based stratification model, applying unbiased recursive partitioning conditional inference tree (URP-CTREE). The primary outcome was the 6-minute walk test at 6 months after injury. Standardized neurological assessments ≤15 days after injury were chosen as predictors. Resulting subgroups were incorporated into a subsequent node-specific analysis to attribute the role of individual lower extremity myotomes for the prognosis of walking function., Results: Using URP-CTREE, the study group of 361 SCI patients was divided into 8 homogeneous subgroups. The node specific analysis uncovered that proximal myotomes L2 and L3 were driving factors for the differentiation between walkers and non-walkers. Distal myotomes L4-S1 were revealed to be responsible for the prognostic distinction of indoor and outdoor walkers (with and without aids)., Conclusion: Stratification of a heterogeneous population with paraplegic SCI into more homogeneous subgroups, combined with the identification of underlying muscle functions prospectively determining the walking outcome, enable potential benefit for application in clinical trials and practice.

After incomplete spinal cord injury (iSCI), the control of lower extremity movements may be affected by impairments in descending corticospinal tract function. Previous iSCI studies demonstrated relatively well-preserved movement control during simple alternating dorsiflections and plantar flexions albeit with severely reduced motor strength and range of motion. This task, however, required comparably limited fine motor control, impeding the sensitivity to assess the modulatory capacity of corticospinal control. Therefore, we introduced a more challenging ankle motor task necessitating complex and dynamic feedback-based movement adjustments to modulate corticospinal drive. Nineteen individuals with iSCI and 22 control subjects performed two different ankle movement tasks: (1) a regular, auditory-guided ankle movement task at a constant frequency as baseline assessment and (2) an irregular, visually guided ankle movement task following a pre-defined trajectory as a more challenging motor task. Both tasks were performed separately and in a randomized order. Electromyography (EMG) and kinematic data were recorded. The EMG frequency characteristics were investigated using wavelet transformations. Control participants exhibited a shift of relative EMG intensity from higher (>100 Hz) to lower frequencies (20-60 Hz) comparing the regular with the irregular movement task. There is evidence that EMG activity within these lower frequencies comprise information on corticospinal drive. The EMG frequency shift was less pronounced for the less impaired leg and absent for the more impaired leg of individuals with iSCI. The precision error during the irregular task was significantly higher for individuals with iSCI (more impaired leg: 12.34 ± 11.14%; less impaired leg: 6.93 ± 2.74%) compared with control participants (4.10 ± 0.84%). These results, along with the walking performance, correlated well with the delta frequency shift between the regular and irregular movement task in the 38 Hz band (corticospinal drive frequency) in the iSCI group, suggesting that task performance is related to the capacity to modulate corticospinal control. The irregular movement task holds promise as a tool for revealing further insights into corticospinal control of single-joint movements. It may serve as a surrogate marker for the assessment of modulatory capacity and the integrity of corticospinal control in individuals with iSCI early after injury and throughout rehabilitation.

Study Design: Multicentre-observational study., Objectives: The 6-minute walk test (6mWT) is an established assessment of walking function in individuals with spinal cord injury (SCI). However, walking 6 min can be demanding for severely impaired individuals. The 2-minute walk test (2mWT) could be an appropriate alternative that has already been validated in other neurological disorders. The aim of this study was to assess construct validity and test-rest reliability of the 2mWT in individuals with SCI. In addition, the influence of walking performance on sensitivity to change of the 2mWT was assessed., Setting: Swiss Paraplegic Center Nottwil, Switzerland; Balgrist University Hospital, Zürich, Switzerland., Methods: Fifty individuals (aged 18-79) with SCI (neurological level of injury: C1-L3, AIS: A-D) were assessed on two test days separated by 1 to 7 days. The first assessment consisted of a 2mWT familiarization, followed by a 2mWT and 10-meter walk test (10MWT) (including the Walking Index for Spinal Cord Injury (WISCI II)) in randomized order. The second assessment consisted of 2mWT and 6mWT in randomized order. Tests were separated by at least 30 min of rest., Results: The interclass correlation coefficient between the 2mWT assessed on the first and second test day was excellent (r = 0.980, p < 0.001). The 2mWT correlated very strongly with the 6mWT (r = 0.992, p < 0.001) and the 10MWT (r = 0.964, p < 0.001), and moderately with the WISCI II (r = 0.571, p < 0.001). Sensitivity to change was slightly affected by walking performance., Conclusion: The 2mWT is a valid and reliable alternative to the 6mWT to measure walking function in individuals with SCI., Trial Registration: NCT04555759., (© 2022. The Author(s).)

The Graded Redefined Assessment of Strength, Sensibility, and Prehension Version 1 (GRASSP v1) is a validated measure of upper extremity impairment shown to be sensitive and responsive for traumatic cervical spinal cord injury (SCI) in both North American (NA) and European (EU) cohorts. The minimal clinically important difference (MCID) is the quantitative change in an assessment scale that patients perceive as being beneficial. Our aim was to establish the MCID of all subtests of the GRASSP v1 for cervical SCI. We prospectively analyzed 127 patients from NA and EU for up to six months after motor complete and incomplete cervical SCI using the GRASSP v1, Spinal Cord Independence Measure, and International Standards of Neurological Classification of Spinal Cord Injury. We used a patient global rating of change and the anchor-based method to calculate MCID of GRASSP v1 at six months post-injury. The MCID was established for the whole group, dividing the sample by "better" and "much better." Improvement in GRASSP v1 Strength and Prehension Performance scores of 13 and 3 are the MCID for the better category, and 19 and 7 are the MCID for the much better category, respectively. The MCID was also established for the motor complete and incomplete groups. Improvement in GRASSP v1 Strength and Prehension Performance scores of 12 and 6 are the MCID for the motor complete group, and 17 and 12 are the MCID for the motor incomplete group, respectively. The GRASSP v1 Strength subscore is the most sensitive for detecting meaningful clinical change in patients and is most closely related to measures of independence. Thus, use of GRASSP v1 Strength and Prehension Performance as measures of change is substantiated by this study.

Introduction: Oncoplastic techniques allow resection of larger tumors, permitting breast conservation in cases otherwise requiring mastectomy. We sought to prospectively compare quality of life (QoL) in patients undergoing oncoplastic surgery as compared to conventional breast conservation (CBC) or mastectomy is lacking., Methods: Patients diagnosed with BIRADS IV-VI lesion were eligible if resection of ≥10% of the breast volume was planned. Patients were allowed to decide whether they wanted to undergo CBC or oncoplastic breast conservation (OBC). Patients who underwent mastectomy and immediate breast reconstruction (IBR) were also included for comparison. The primary endpoint was breast self-esteem using the Breast Image Scale (BIS) at 12 months, secondary endpoints were perioperative morbidity and QoL using the BREAST-Q questionnaire., Results: From 2011 to 2016, 205 patients were included in the study. 116 patients (56.6%) received CBC, 46 (22.4%) OBC and 43 (21%) MIBR. Women in the OBC group were more likely to have tumors ≥ 2 cm than those in the CBC group (34.7% vs. 17.5%, respectively). Women who underwent MIBR were more likely to have tumors > 5 cm than those in the CBC and OBC groups (23% vs 1% and 10%, respectively). The BIS and BREAST-Q improved in each group after 12 months but did not differ significantly between groups at any time point. Surgical complications (seroma, bleeding, infection, necrosis) were numerically more likely in the OBC and MIBR groups., Conclusion: OBC and the MIBR allow for resection of larger tumors with a similar quality of life as CBC., (Copyright © 2022. Published by Elsevier Ltd.)

Inertial Measurement Units (IMUs) have gained popularity in gait analysis and human motion tracking, and they provide certain advantages over stationary line-of-sight-dependent Optical Motion Capture (OMC) systems. IMUs appear as an appropriate alternative solution to reduce dependency on bulky, room-based hardware and facilitate the analysis of walking patterns in clinical settings and daily life activities. However, most inertial gait analysis methods are unpractical in clinical settings due to the necessity of precise sensor placement, the need for well-performed calibration movements and poses, and due to distorted magnetometer data in indoor environments as well as nearby ferromagnetic material and electronic devices. To address these limitations, recent literature has proposed methods for self-calibrating magnetometer-free inertial motion tracking, and acceptable performance has been achieved in mechanical joints and in individuals without neurological disorders. However, the performance of such methods has not been validated in clinical settings for individuals with neurological disorders, specifically individuals with incomplete Spinal Cord Injury (iSCI). In the present study, we used recently proposed inertial motion-tracking methods, which avoid magnetometer data and leverage kinematic constraints for anatomical calibration. We used these methods to determine the range of motion of the Flexion/Extension (F/E) hip and Abduction/Adduction (A/A) angles, the F/E knee angles, and the Dorsi/Plantar (D/P) flexion ankle joint angles during walking. Data (IMU and OMC) of five individuals with no neurological disorders (control group) and five participants with iSCI walking for two minutes on a treadmill in a self-paced mode were analyzed. For validation purposes, the OMC system was considered as a reference. The mean absolute difference (MAD) between calculated range of motion of joint angles was 5.00°, 5.02°, 5.26°, and 3.72° for hip F/E, hip A/A, knee F/E, and ankle D/P flexion angles, respectively. In addition, relative stance, swing, double support phases, and cadence were calculated and validated. The MAD for the relative gait phases (stance, swing, and double support) was 1.7%, and the average cadence error was 0.09 steps/min. The MAD values for RoM and relative gait phases can be considered as clinically acceptable. Therefore, we conclude that the proposed methodology is promising, enabling non-restrictive inertial gait analysis in clinical settings.

Background: New therapeutic approaches in neurological disorders are progressing into clinical development. Past failures in translational research have underlined the critical importance of selecting appropriate inclusion criteria and primary outcomes. Narrow inclusion criteria provide sensitivity, but increase trial duration and cost to the point of infeasibility, while broader requirements amplify confounding, increasing the risk of trial failure. This dilemma is perhaps most pronounced in spinal cord injury (SCI), but applies to all neurological disorders with low frequency and/or heterogeneous clinical manifestations., Objective: Stratification of homogeneous patient cohorts to enable the design of clinical trials with broad inclusion criteria., Methods: Prospectively-gathered data from patients with acute cervical SCI were analysed using an unbiased recursive partitioning conditional inference tree (URP-CTREE) approach. Performance in the 6-minute walk test at 6 months after injury was classified based on standardized neurological assessments within the first 15 days of injury. Functional and neurological outcomes were tracked throughout rehabilitation up to 6 months after injury., Results: URP-CTREE identified homogeneous outcome cohorts in a study group of 309 SCI patients. These cohorts were validated by an internal, yet independent, validation group of 172 patients. The study group cohorts identified demonstrated distinct recovery profiles throughout rehabilitation. The baseline characteristics of the analysed groups were compared to a reference group of 477 patients., Conclusion: URP-CTREE enables inclusive trial design by revealing the distribution of outcome cohorts, discerning distinct recovery profiles and projecting potential patient enrolment by providing estimates of the relative frequencies of cohorts to improve the design of clinical trials in SCI and beyond.

Introduction: Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4)., Methods: Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed., Results: A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 ("ink on tumor") in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups., Conclusions: Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI., (© 2021. The Author(s).)

Background: Many patients with neurological movement disorders fear to fall while performing postural transitions without assistance, which prevents them from participating in daily life. To overcome this limitation, multi-directional Body Weight Support (BWS) systems have been developed allowing them to perform training in a safe environment. In addition to overground walking, these innovative/novel systems can assist patients to train many more gait-related tasks needed for daily life under very realistic conditions. The necessary assistance during the users' movements can be provided via task-dependent support designs. One remaining challenge is the manual switching between task-dependent supports. It is error-prone, cumbersome, distracts therapists and patients, and interrupts the training workflow. Hence, we propose a real-time motion onset recognition model that performs automatic support switching between standing-up and sitting-down transitions and other gait-related tasks (8 classes in total)., Methods: To predict the onsets of the gait-related tasks, three Inertial Measurement Units (IMUs) were attached to the sternum and middle of outer thighs of 19 controls without neurological movement disorders and two individuals with incomplete Spinal Cord Injury (iSCI). The data of IMUs obtained from different gait tasks was sent synchronously to a real-time data acquisition system through a custom-made Bluetooth-EtherCAT gateway. In the first step, data was applied offline for training five different classifiers. The best classifier was chosen based on F1-score results of a Leave-One-Participant-Out Cross-Validation (LOPOCV), which is an unbiased way of testing. In a final step, the chosen classifier was tested in real time with an additional control participant to demonstrate feasibility for real-time classification., Results: Testing five different classifiers, the best performance was obtained in a single-layer neural network with 25 neurons. The F1-score of [Formula: see text] and [Formula: see text] are achieved on testing using LOPOCV and test data ([Formula: see text], participants = 20), respectively. Furthermore, the results from the implemented real-time classifier were compared with the offline classifier and revealed nearly identical performance (difference = [Formula: see text])., Conclusions: A neural network classifier was trained for identifying the onset of gait-related tasks in real time. Test data showed convincing performance for offline and real-time classification. This demonstrates the feasibility and potential for implementing real-time onset recognition in rehabilitation devices in future., (© 2022. The Author(s).)

Introduction: Spinal cord injury (SCI) is a devastating condition with immediate impact on the individual's health and quality of life. Major functional recovery reaches a plateau 3-4 months after injury despite intensive rehabilitative training. To enhance training efficacy and improve long-term outcomes, the combination of rehabilitation with electrical modulation of the spinal cord and brain has recently aroused scientific interest with encouraging results. The mesencephalic locomotor region (MLR), an evolutionarily conserved brainstem locomotor command and control centre, is considered a promising target for deep brain stimulation (DBS) in patients with SCI. Experiments showed that MLR-DBS can induce locomotion in rats with spinal white matter destructions of >85%., Methods and Analysis: In this prospective one-armed multi-centre study, we investigate the safety, feasibility, and therapeutic efficacy of MLR-DBS to enable and enhance locomotor training in severely affected, subchronic and chronic American Spinal Injury Association Impairment Scale C patients in order to improve functional recovery. Patients undergo an intensive training programme with MLR-DBS while being regularly followed up until 6 months post-implantation. The acquired data of each timepoint are compared with baseline while the primary endpoint is performance in the 6-minute walking test. The clinical trial protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials checklist., Ethics and Dissemination: This first in-man study investigates the therapeutic potential of MLR-DBS in SCI patients. One patient has already been implanted with electrodes and underwent MLR stimulation during locomotion. Based on the preliminary results which promise safety and feasibility, recruitment of further patients is currently ongoing. Ethical approval has been obtained from the Ethical Committee of the Canton of Zurich (case number BASEC 2016-01104) and Swissmedic (10000316). Results will be published in peer-reviewed journals and presented at conferences., Trial Registration Number: NCT03053791., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Deficient ankle control after incomplete spinal cord injury (iSCI) often accentuates walking impairments. Transcutaneous electrical spinal cord stimulation (tSCS) has been shown to augment locomotor activity after iSCI, presumably due to modulation of spinal excitability. However, the effects of possible excitability modulations induced by tSCS on ankle control have not yet been assessed. This study investigated the immediate (i.e., without training) effects during single-sessions of tonic tSCS on ankle control, spinal excitability, and locomotion in ten individuals with chronic, sensorimotor iSCI (American Spinal Injury Association Impairment Scale D). Participants performed rhythmic ankle movements (dorsi- and plantar flexion) at a given rate, and irregular ankle movements following a predetermined trajectory with and without tonic tSCS at 15 Hz, 30 Hz, and 50 Hz. In a subgroup of eight participants, the effects of tSCS on assisted over-ground walking were studied. Furthermore, the activity of a polysynaptic spinal reflex, associated with spinal locomotor networks, was investigated to study the effect of the stimulation on the dedicated spinal circuitry associated with locomotor function. Tonic tSCS at 30 Hz immediately improved maximum dorsiflexion by +4.6° ± 0.9° in the more affected lower limb during the rhythmic ankle movement task, resulting in an increase of +2.9° ± 0.9° in active range of motion. Coordination of ankle movements, assessed by the ability to perform rhythmic ankle movements at a given target rate and to perform irregular movements according to a trajectory, was unchanged during stimulation. tSCS at 30 Hz modulated spinal reflex activity, reflected by a significant suppression of pathological activity specific to SCI in the assessed polysynaptic spinal reflex. During walking, there was no statistical group effect of tSCS. In the subgroup of eight assessed participants, the three with the lowest as well as the one with the highest walking function scores showed positive stimulation effects, including increased maximum walking speed, or more continuous and faster stepping at a self-selected speed. Future studies need to investigate if multiple applications and individual optimization of the stimulation parameters can increase the effects of tSCS, and if the technique can improve the outcome of locomotor rehabilitation after iSCI.

Locomotor recovery after incomplete spinal cord injury (iSCI) is influenced by spinal and supraspinal networks. Conventional clinical gait analysis fails to differentiate between these components. There is evidence that corticospinal control is enhanced during targeted walking, where each foot must be continuously placed on visual targets in randomized order. This study investigates the potential of targeted walking in the functional assessment of corticospinal integrity. Twenty-one controls and 16 individuals with chronic iSCI performed normal and targeted walking on a treadmill while electromyograms (EMGs) and kinematics were recorded. Precision (% of accurate foot placements) in targeted walking was significantly lower in individuals with iSCI (82.9 ± 14.7%, controls: 94.9 ± 4.0%). Although the overall kinematic pattern was comparable between walking conditions, controls showed significantly higher semitendinosus (ST) activity before heel-strike during targeted walking. This was accompanied by a shift of relative EMG intensity from 90-120 Hz to lower frequencies of 20-60 Hz, previously associated with corticospinal control of muscle activity. Targeted walking in individuals with iSCI evoked smaller EMG changes, suggesting that the switch to more corticospinal control is impaired. Accordingly, mildly impaired iSCI individuals revealed higher adaptations to the targeted walking task than more-impaired individuals. Recording of EMGs during targeted walking holds potential as a research tool to reveal further insights into the neuromuscular control of locomotion. It also complements findings of pre-clinical studies and is a promising novel surrogate marker of integrity of corticospinal control in individuals with iSCI and other neurological impairments. Future studies should investigate its potential for diagnosis or tracking recovery during rehabilitation.

Accurate functional outcome measures are critical for both clinical trials and routine patient assessments. Many functional outcomes improve with test repetition, a phenomenon that can confound the findings of longitudinal assessments. In this viewpoint, we tackle the poorly considered issue of practice effects in prevailing clinical walking tests based on current literature, while also presenting the original data from our own work, in which we investigated practice effects in the timed 25-foot walk (T25FW), timed-up and go (TUG), and 2-minute walk test (2MWT). In these tests, performed on 3 consecutive days in 10 patients with multiple sclerosis and 40 healthy controls, we observed significant practice effects in several established walking outcomes, including a 9.0% improvement in patients' TUG performance ( p  = 0.0146). Pre-training in these walking tests prior to baseline measurement may mitigate practice effects, thereby improving the accuracy and value of their repeated use in research and clinical settings.

Background: Body weight support systems with three or more degrees of freedom (3-DoF) are permissive and safe environments that provide unloading and allow unrestricted movement in any direction. This enables training of walking and balance control at an early stage in rehabilitation. Transparent systems generate a support force vector that is near vertical at all positions in the workspace to only minimally interfere with natural movement patterns. Patients with impaired balance, however, may benefit from additional mediolateral support that can be adjusted according to their capacity. An elegant solution for providing balance support might be by rendering viscous damping along the mediolateral axis via the software controller. Before use with patients, we evaluated if control-rendered mediolateral damping evokes the desired stability enhancement in able-bodied individuals., Methods: A transparent, cable-driven robotic body weight support system (FLOAT) was used to provide transparent body weight support with and without mediolateral damping to 21 able-bodied volunteers while walking at preferred gait velocity on a treadmill. Stability metrics reflecting resistance to small and large perturbations were derived from walking kinematics and compared between conditions and to free walking., Results: Compared to free walking, the application of body weight support per-se resulted in gait alterations typically associated with body weight support, namely increased step length and swing phase. Frontal plane dynamic stability, measured by kinematic variability and nonlinear dynamics of the center of mass, was increased under body weight support, indicating reduced balance requirements in both damped and undamped support conditions. Adding damping to the body weight support resulted in a greater increase of frontal plane stability., Conclusion: Adding mediolateral damping to 3-DoF body weight support systems is an effective method of increasing frontal plane stability during walking in able-bodied participants. Building on these results, adjustable mediolateral damping could enable therapists to select combinations of unloading and stability specifically for each patient and to adapt this in a task specific manner. This could extend the impact of transparent 3-DoF body weight support systems, enabling training of gait and active balance from an early time point onwards in the rehabilitation process for a wide range of mobility activities of daily life.

Myotonic Dystrophy Type 1 (DM1) is the most frequent hereditary, adult-onset muscular dystrophy. Nevertheless, DM1-associated cognitive-motor impairments have not been fully characterized so far. This study aimed at profiling cognitive and locomotor dysfunctions in these patients. In addition, cognitive-motor interactions were assessed using a dual-task paradigm. Comprehensive cognitive-motor impairment profiles were generated for 19 patients with DM1 and 19 healthy subjects by thorough clinical, biomechanical and neuropsychological examinations. Detailed gait analysis was performed using a 3D motion capture system, whereas cognitive function was assessed using a standardized neuropsychological test battery. Patients with DM1 showed impaired functional mobility, gait velocity and endurance. DM1-related gait pathology was mainly characterized by enhanced dynamic instability, gait variability, and restricted ankle dorsiflexion. Patients' cognitive impairments particularly concerned attentional functions. Dual-task conditions induced gait deviations that slightly differed between patients and controls. DM1-associated cognitive impairments correlated with reduced functional mobility and impaired ankle dorsiflexion. Patients with DM1 revealed significant impairments of walking function, balance and cognitive performance. Differential cognitive-motor interference and significant interactions between cognitive and motor dysfunctions point towards a prominent role of cognition in gait performance of patients with DM1., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: While "no tumour on ink" is an accepted margin width for R 0 resection in primary surgery, it's unclear if it's oncologically safe after neoadjuvant chemotherapy (NAC). Only limited data demonstrate that surgery within new margins in cases of a pathological complete response (pCR) is safe. We therefore investigated the influence of different margins and pCR on local recurrence and survival rates after NAC., Methods: We retrospectively analysed data of 406 women with invasive breast cancer, treated with NAC and breast-conserving therapy between 1994 and 2014 in two certified Austrian breast health centres. We compared R ≤ 1 mm, R > 1 mm and RX (pCR) for local recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS)., Results: After a median follow-up of 84.3 months, the 5-year LRFS (R ≤ 1 mm: 94.2%, R > 1 mm: 90.6%, RX: 95.0%; p = 0.940), the 5-year DFS (R ≤ 1 mm: 71.9%, R > 1 mm: 74.1%, RX: 87.2%; p = 0.245) and the 5-year OS (R ≤ 1 mm: 85.1%, R > 1 mm: 88.0%, RX: 96.4%; p = 0.236) did not differ significantly between narrow, wide, nor RX resections. Regarding DFS and OS, a negative nodal status reduced the hazard ratio significantly., Conclusion: There is no significant difference in LRFS, DFS and OS comparing close, wide or unknown margins after pCR. We suggest that resection in new margins after NAC is safe according to "no tumour on ink". Resection of the clipped area in cases of pCR is emphasized.

An abdominal aortic aneurysm (AAA) is a relatively common, life-threatening disease prevalent in persons over the age of 65. In recent years, an increasing number of studies have suggested that pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), may serve as important regulators in the development of AAAs. In this study, we evaluated the TLR2 and TLR4 expression in the aortic wall and blood of patients with AAA. The TLR2 and TLR4 mRNA expression were significantly higher in the blood of patients with AAA than in the blood of healthy volunteers (p = 0.009 and p = 0.010, respectively). The expression of TLR2 and TLR4 transcripts was also higher in the blood compared with the aortic wall tissue of AAA patients (p = 0.001 for both). Higher TLR2 protein expression was observed in the aortic wall of AAA patients compared with the blood (p = 0.026). A significantly higher concentration of TNF-α and IL-4 in patients with AAA than in healthy volunteers (p < 0.001 for both) was noticed. This study suggests that TLR2 may play a role in the inflammatory response in the aorta, both locally and systemically, in patients with AAA.

Background: After a neurological injury, mobility focused rehabilitation programs intensively train walking on treadmills or overground. However, after discharge, quite a few patients are not able to independently negotiate stairs, a real-world task with high physical and psychological demands and a high injury risk. To decrease fall risk and improve patients' capacity to navigate typical environments, early stair negotiation training can help restore competence and confidence in safe stair negotiation. One way to enable early training in a safe and permissive environment is to unload the patient with a body weight support system. We here investigated if unloaded stair negotiation complies with basic locomotor principles, in terms of enabling performance of a physiological movement pattern with minimal compensation., Methods: Seventeen able-bodied participants were unloaded with 0-50% bodyweight during self-paced ascent and descent of a 4-tread staircase. Spatio-temporal parameters, joint ranges of motion, ground reaction forces and myoelectric activity in the main lower limb muscles of participants were compared between unloading levels. Likelihood ratio tests of separated linear mixed models of the investigated outcomes assessed if unloading affects the parameters in general. Subsequent post-hoc testing revealed which levels of unloading differed from unsupported stair negotiation., Results: Unloading affected walking velocity, joint ranges of motion, vertical ground reaction force parameters and myoelectric activity in all investigated muscles for stair ascent and descent while step width and single support duration were only affected during ascent. A reduction with increasing levels of body weight support was seen in walking velocity (0.07-0.12 m/s), ranges of motion of the knee and hip (2-10°), vertical ground reaction force peaks (10-70%) and myoelectric activity (17-70%). An increase with unloading was only seen during ascent for ankle range of motion and tibialis anterior activity at substantial unloading., Conclusions: Body weight support facilitates stair negotiation by providing safety and support against gravity. Although unloading effects are present in most parameters, up to 30% body weight support these changes are small, and no dysfunctional patterns are introduced. Body weight support therefore fulfills all the necessary requirements for early stair negotiation training.

Context: GRASSP Version 1 (GV1) was developed in 2010, is an upper extremity measure specifically designed to assess recovery after traumatic tetraplegia. A second version was developed to reduce length of the test and refine instructions/standardization. The purpose of this post hoc analysis was to calculate psychometric properties of GRASSP Version 2 (GV2). Design/Setting: A post-hoc analysis of datasets for the GRASSP cross-sectional ( n  = 72 chronic,) and longitudinal ( n  = 127 acute) studies was conducted. Reliability, validity and MDD were calculated from the chronic sample and responsiveness was re-calculated from the longitudinal sample. Both studies were observational. Participants: A chronic sample ( n  = 72) and acute longitudinal sample ( n  = 127) of individuals with traumatic tetraplegia (AIS A to D, NLI C2 to C8) were studied. Outcome Measures: GV1, the Spinal Cord Independence Measure III (SCIM), International Standards of Neurological Classification of Spinal Cord Injury (ISNCSCI) were administered in both studies at all centers and the Capabilities of the Upper Extremity Questionnaire (CUE-Q) was administered in North American sites only. GRASSP-Palmar Sensation, GRASSP-Prehension Performance subtest items included in GV2 were re-analyzed for reliability; validity, MDD and responsiveness. Results: Inter-rater and test-retest reliability for all subtests ranged between 0.849-0.971 and 0.950-0.971 respectively. Concurrent validity between domains of GV2 were positively and moderately (0.530-0.830, P  < 0.0001) correlated to SCIM, SCIM self-care subscore (SS) and CUE-Q. MDD values were 4 and 3 points for sensation and prehension performance (single side). Responsiveness values were .84-.88 for GR-Sens and .93-1.22 for GR-PP respectively. Conclusions: GV2 retains excellent psychometric properties as does GV1.

Treadmill-based gait analysis is widely used to investigate walking pathologies and quantify treatment effects on locomotion. Differential sensorimotor conditions during overground vs. treadmill walking necessitate initial familiarization to treadmill walking. Currently, there is no standardized treadmill acclimatization protocol and insufficient familiarization potentially confounds analyses. We monitored initial adaptations to treadmill walking in 40 healthy adults. Twenty-six walking parameters were assessed over 10 minutes with marker-based kinematic analysis and acclimatization profiles were generated. While 16 walking parameters demonstrated initial acclimatization followed by plateau performance, ten parameters remained stable. Distal lower limb control including ankle range of motion, toe trajectory and foot clearance underwent substantial adaptations. Moreover, intralimb coordination and gait variability also demonstrated acclimatization, while measures of symmetry and interlimb coordination did not. All parameters exhibiting a plateau after acclimatization did so within 6-7 minutes (425 strides). Older participants and those naïve to treadmill walking showed adaptations with higher amplitudes but over similar timescales. Our results suggest a minimum of 6 minutes treadmill acclimatization is required to reach a stable performance, and that this should suffice for both older and naïve healthy adults. The presented data aids in optimizing treadmill-based gait analysis and contributes to improving locomotor assessments in research and clinical settings.