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Surgical repair of recurrent tracheoesophageal fistula has a high risk of complications. Therefore, various endoscopic techniques have been used to avoid complications.To understand the usefulness of trichloroacetic acid endoscopic application for the treatment of recurrent tracheoesophageal fistula.An observational, descriptive, retrospective, case-series-based study was carried out in a tertiary pediatric hospital. Records of patients with recurrent tracheoesophageal fistula from 2015 to 2021 were reviewed. All patients within this period underwent brushing and trichloroacetic acid application.Mean time of recurrent tracheoesophageal fistula occurrence was 4.8 months (range: 1-19.2). Two patients had a small fistula (less than 4 mm), three patients had a medium fistula (4 mm), and two patients had a large fistula (more than 4 mm). Mean sessions for fistula closure were 2.2 (range: 1-4). Mean time between procedures was 22 days (range: 14-30). Mean follow-up since fistula closure confirmation was 33 months (range: 9-72), during which no recurrences were noted.Endoscopic management of recurrent transesophageal fistula with trichloroacetic acid is a safe and effective procedure. Brushing and trichloroacetic acid combined improve success rates. Fistulas over 4 mm in diameter require more procedures. However, a larger patient cohort and a longer follow-up period are needed to confirm this.La reparación quirúrgica de la fístula traqueoesofágica recurrente tiene alto riesgo de complicaciones por lo que se han utilizado diversas técnicas endoscópicas para evitarlas.Conocer la utilidad de la aplicación endoscópica de ácido tricloroacético para el tratamiento de la fístula traqueoesofágica recurrente.Estudio observacional, descriptivo y retrospectivo, tipo de serie de casos en un hospital pediátrico de tercer nivel. Se revisaron los expedientes de pacientes con fístula traqueoesofágica recurrente de 2015 a 2021. En todos los pacientes durante este periodo se realizó cepillado y aplicación de ácido tricloroacético.El tiempo medio de aparición de la fístula traqueoesofágica recurrente fue de 4,8 meses (rango 1-19,2). Dos con fístula pequeña (menor a 4 mm), tres con fístula mediana (4 mm) y dos con fístula grande (mayor a 4 mm). El número medio de sesiones para cerrar la fístula fue 2,2 veces (rango 1-4). El intervalo medio entre procedimientos fue 22 días (rango 14-30). El tiempo medio de seguimiento desde la confirmación de cierre de la fistula fue de 33 meses (rango 9-72), periodo de tiempo donde no se observó recurrencia del cuadro.El manejo endoscópico de la fístula traqueoesofágica recurrente con la aplicación de ácido tricloroacético es un procedimiento seguro y efectivo. La técnica de cepillado y aplicación de ácido tricloroacético mejora la efectividad de éxito. La fístula mayor de 4 mm de diámetro requiere mayor número de procedimientos; sin embargo, se requiere mayor número de pacientes y mayor tiempo de seguimiento para poder aseverar esta opinión.

COVID-19; Pèrdua d'olfacte; Prova de l'olfacte COVID-19; Loss of smell; Smell test COVID-19; Pérdida de olfato; Prueba del olfato Background and objective: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. Methods: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. Results: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P

Background: Few odor tests have been developed for children. Objectives: The aim of the present study was to develop and validate a simple and quick olfactory test to evaluate odor identification and threshold in a Spanish pediatric population. Methods: The Pediatric Barcelona Olfactory Test-6 (pBOT-6) consisted of a set of 6 odorants for a forced choice identification test and a 6-dilution phenyl ethyl alcohol geometric series for the threshold test. The pBOT-6 was compared with the Universal Sniff test (a validated international pediatric smell test) in 131 healthy Spanish volunteers aged 6-17 years. A Bland-Altman plot was used to determine the agreement between the 2 tests. Reliability was analyzed in 15 volunteers using the intraclass correlation coefficient. Normative data were obtained, and 8 children diagnosed with subjective loss of smell were tested for validation. Results: The Bland-Altman analysis demonstrated a minimal bias of –1.71% with upper and lower limits of agreement of –31.1% and 27.6%, respectively. The intraclass correlation coefficient was 0.83 (95%CI, 0.6-0.96) for the identification test and 0.73 (95%CI, 0.36-0.9) for the threshold test, with excellent and good consistency between measurements over time. Mean pBOT-6 scores were significantly higher in healthy volunteers than in patients with loss of smell. Discrimination between normosmia and loss of smell was achieved with a sensitivity of 96.9% and a specificity of 100%. Conclusions: pBOT-6 offers an effective and fast method that is useful in clinical routine to distinguish, with high sensitivity and specificity, between pediatric patients with normosmia and those with loss of smell.

PSA is the most widely used diagnosticand prognostic biomarker in prostate cancer (PCa).However, its lack of specificity has generated the needto search for new complementary markers. In thisscenario, blood plasma constitutes one of the sourcesof search for new markers, which have been tried tobe combined with PSA and other clinical variables inorder to develop tests that increase their diagnosticspecificity.This narrative review of the literature provides anoverview of commercially available plasma biomarkers and tests for use in different clinical settingsfor PCa. The most studied markers to help select theappropriate patients for initial and / or repeat biopsyhave been: PHI, 4K, STHLM3. These markers havebeen oriented towards the diagnosis of the so-calledclinically signifi cant PCa, trying to validate and calibratetheir algorithms in different populations. Giventhe development and evolution in the diagnosis of PCa,there is still a lack of evidence of the impact of magneticresonance imaging (MRI) when used in combinationwith these new markers, as well as its possiblerole in the screening of the disease and not only in theearly diagnosis process. Furthermore, there are only asmall number of studies that have directly comparedthese tests with each other and with PSA, so there isnot enough evidence to know which test has the bestproperties in each clinical scenario. In order to clarifythe true diagnostic role of these new biomarkers, newprospective, comparative studies in different populationsare absolutely necessary to evaluate their clinicalutility in combination with MRI and fusion biopsy.El PSA es el biomarcador diagnóstico ypronóstico más ampliamente utilizado en cáncer deprostata (CaP). Sin embargo, su falta de especificidadha generado la necesidad de buscar nuevos marcadorescomplementarios. En este escenario, el plasmasanguíneo constituye una de las fuentes de búsquedade nuevos marcadores, los cuales han tratado decombinarse con el PSA y otras variables clínicas conel objeto de desarrollar tests que aumentaran su especificidaddiagnóstica.En esta revisión narrativa de la literatura se proporcionauna descripción general de los biomarcadoresplasmáticos y tests disponibles comercialmentepara ser utilizados en diferentes contextos clínicosdel CaP. Los test más estudiados para ayudar a seleccionarlos pacientes adecuados para la biopsia inicialy / o repetida han sido: PHI, 4K, STHLM3. Estos testse han orientado hacia el diagnóstico del denominadoCaP clínicamente significativo, intentando validary calibrar sus algoritmos en diferentes poblaciones.Dado el desarrollo y evolución en el diagnóstico deCaP, aún existe una falta de evidencia del impacto de la resonancia magnética (RM) al ser empleada encombinación con estos nuevos marcadores, así comosu posible papel en el screening de la enfermedad yno solo en el proceso de diagnóstico precoz. Además,solo se dispone de una pequeña cantidad de estudiosque hayan comparado directamente estos test entreellos y con el PSA, de modo que no existe evidenciasuficiente para saber qué test tiene mejores propiedadesen cada escenario clínico. En el escenarioactual, para poder aclarar el verdadero papel diagnósticode estos nuevos biomarcadores, son absolutamentenecesarios nuevos estudios prospectivos,comparativos y en diferentes poblaciones, que evalúensu utilidad clínica en combinación con la RM yla biopsia fusión.

Brain-Computer Interface systems can contribute to a vast set of applications such as overcoming physical disabilities in people with neural injuries or hands-free control of devices in healthy individuals. However, having systems that can accurately interpret intention online remains a challenge in this field. Robust and data-efficient decoding-despite the dynamical nature of cortical activity and causality requirements for physical function-is among the most important challenges that limit the widespread use of these devices for real-world applications. Here, we present a causal, data-efficient neural decoding pipeline that predicts intention by first classifying recordings in short sliding windows. Next, it performs weighted voting over initial predictions up to the current point in time to report a refined final prediction. We demonstrate its utility by classifying spiking neural activity collected from the human posterior parietal cortex for a cue, delay, imaginary motor task. This pipeline provides higher classification accuracy than state-of-the-art time windowed spiking activity based causal methods, and is robust to the choice of hyper-parameters.

The treatment of metastatic castration-resistant prostate cancer (mCRPC) has changed significantly in recent years. Inhibitors of androgen receptors have shown especially significant benefits in overall (OS) and progression-free survival (PFS), with a good toxicity profile. Treatment selection depends on the patient’s individual clinical, radiological, and biological characteristics. To describe treatment outcomes (efficacy, toxicity) in a cohort of patients with mCRPC in Spain. Multicenter, retrospective study of patients with mCRPC included in a database of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR). Metastatic CRPC was defined according to the prostate cancer working group 3 (PCWG3) criteria. The Kaplan–Meier technique was used to evaluate OS and the Common Terminology Criteria for Adverse Events (CTCAE, v.4.0) were used to assess toxicity. Univariate and multivariate Cox regression analyses were performed to identify the factors significantly associated with OS. A total of 314 patients from 17 hospitals in Spain diagnosed with mCRPC between June 2010 and September 2017 were included in this study. Mean age at diagnosis was 68 years (range 45–89). At a median follow-up of 35 months, OS at 1, 3, and 5 years were 92%, 38%, and 28%, respectively. Grades 1–2 and grade 3 toxicity rates were, respectively, 68% and 19%. No grade 4 toxicities were observed. On the multivariate analysis, the following factors were significantly associated with OS: age (hazard ratio [HR] 0.42, p = 0.010), PSA value at diagnosis of mCRPC (HR 0.55, p = 0.008), and Gleason score (HR 0.61, p = 0.009). Age, Gleason score, and PSA at diagnosis of mCRPC are independently associated with overall survival in patients with mCRPC. The efficacy and toxicity outcomes in this patient cohort treated in radiation oncology departments in Spain are consistent with previous reports.

Amputation represents a drastic impact on the patient’s body and perception. This cross-sectional study aims to analyse the aesthetic concern represented by body image, self-esteem and quality of life in patients with unilateral transtibial amputations of lower limbs compared to control group. People living with amputations present lower average levels than controls in all subscales of the SF-36 (Short Form 36 Health Survey) quality of life questionnaire, and in both the physical component summary and the mental component summary, although the difference is not statistically significant in the latter. These patients present a significantly lower mean score (p = 0.002) in the MBSRQ (Body-Self Relations Questionnaire) body image questionnaire: 2.64 ± 0.49 opposed to 3.16 ± 0.55 in controls. People living with amputations had a lower mean score on the Rosenberg Self-Esteem scale than controls (34.44 ± 4.61 v 36.04 ± 3.63). The results also show that amputation has a significant influence on the BI (Body image) of patients with unilateral transtibial amputations. SE (Self-Esteem) seems to be an aspect that is not significantly affected by lower limb amputation, although these patients scored a lower mean on the RSE scale compared to the control group. We consider it is highly relevant to assess QoL (Quality of life), BI and SE in patients after a lower limb amputation process.

To explore the feasibility of image-guided and respiratory-gated Stereotactic Body Radiation Therapy (SBRT) for Accelerated Partial Breast Irradiation (APBI) in patients with very early breast cancer.Selected patients with early breast carcinoma after breast-conserving surgery were enrolled in this phase II trial. A fiducial marker was percutaneously placed close to surgical bed and five external fiducials were set on the skin. A CT scan for planning was acquired at free breathing. The treatment was planned and DVH were assessed according to international recommendations. Prescription dose was 30 Gy in five consecutive fractions of 6 Gy. A 6MV monoenergetic LINAC (linear accelerator) that combines stereoscopic X-ray imaging system and ExacTrac Adaptive Gating technique was used. PTV (planning target volume) intrafraction motion was controlled and PTV was irradiated in a selected gated area of the respiratory cycle. Shifts for a correct, gated set-up were calculated and automatically applied.Between April 2013 and October 2015, a total of 23 patients were included. The median tumor size was 12 mm. The mean PTV volume was 114 cc. The mean ipsilateral lung V9 Gy was 2.2% and for left-sided breast cancers, the volume of the heart receiving 1.5 Gy was 11.5%. Maximum skin dose was 30.8 Gy. Acute toxicity was grade1 in all the patients and 100% experienced excellent/good breast cosmesis outcomes. With a median follow-up of 66 months (range 8-99 months) local-relapse-free-survival reaches 100%. One patient developed a second breast cancer outside the treated quadrant after 25.1 months.APBI with SBRT and ExacTrac Adaptive Gating System was feasible. The acute and late toxicities were almost null and cosmesis was excellent. We also found that the margins of 5 mm applied from CTV to PTV were sufficient to compensate for geometric uncertainties.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). Patients and methods VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and 1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. Results Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. Conclusions BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy, This work was supported by Roche Farma S.A (no grant number). Medical writing support was funded by Roche Farma S.A and provided by H. Lamb and L. Miller of Miller Medical Communications Ltd.

Prostate cancer is the most commonly diagnosed cancer among men around the world. Radiotherapy is a standard of care treatment option for men with localized prostate cancer. Over the years, radiation delivery modalities have contributed to increased precision of treatment, employing radiobiological insights to shorten the overall treatment time, improving the control of the disease without increasing toxicities. Stereotactic body radiation therapy (SBRT) represents an extreme form of hypofractionated radiotherapy in which treatment is usually delivered in 1–5 fractions. This review assesses the main efficacy and toxicity data of SBRT in non-metastatic prostate cancer and discusses the potential to implement this scheme in routine clinical practice. Sin financiación 3.109 JCR (2021) Q3, 177/245 Oncology 0.926 SJR (2021) Q3, 126/369 Oncology No data IDR 2020 UEM

Key points It is theorized that the nervous system controls groups of muscles together as functional units, or 'synergies', resulting in correlated electromyographic (EMG) signals among muscles. However, such correlation does not necessarily imply group-level neural control. Oscillatory synchronization (coherence) among EMG signals implies neural coupling, but it is not clear how this relates to control of muscle synergies. EMG was recorded from seven arm muscles of 10 adult participants rotating an upper limb ergometer, and EMG-EMG coherence, EMG amplitude correlations and their relationship with each other were characterized. A novel method to derive multi-muscle synergies from EMG-EMG coherence is presented and these are compared with classically defined synergies. Coherent alpha-band (8-16 Hz) drive was strongest among muscles whose gross activity levels are well correlated within a given task. The cross-muscle distribution and temporal modulation of coherent alpha-band drive suggests a possible role in the neural coordination/monitoring of synergies. Abstract During movement, groups of muscles may be controlled together by the nervous system as an adaptable functional entity, or 'synergy'. The rules governing when (or if) this occurs during voluntary behaviour in humans are not well understood, at least in part because synergies are usually defined by correlated patterns of muscle activity without regard for the underlying structure of their neural control. In this study, we investigated the extent to which comodulation of muscle output (i.e. correlation of electromyographic (EMG) amplitudes) implies that muscles share intermuscular neural input (assessed via EMG-EMG coherence analysis). We first examined this relationship among pairs of upper limb muscles engaged in an arm cycling task. We then applied a novel multidimensional EMG-EMG coherence analysis allowing synergies to be characterized on the basis of shared neural drive. We found that alpha-band coherence (8-16 Hz) is related to the degree to which overall muscle activity levels correlate over time. The extension of this coherence analysis to describe the cross-muscle distribution and temporal modulation of alpha-band drive revealed a close match to the temporal and structural features of traditionally defined muscle synergies. Interestingly, the coherence-derived neural drive was inversely associated with, and preceded, changes in EMG amplitudes by ∼200 ms. Our novel characterization of how alpha-band neural drive is dynamically distributed among muscles is a fundamental step forward in understanding the neural origins and correlates of muscle synergies.

Conventional post-prostatectomy radiation therapy comprises 6.5-8 weeks of treatment, therefore, hypofractionated and shortened schemes arouse increasing interest. We describe our experience regarding feasibility and clinical outcome of a post-prostatectomy moderate hypofractionated image-guided radiotherapy schedule MATERIALS AND METHODS: From Oct 2015-Mar 2020, 113 patients, median age of 62 years-old (range 45-76) and prostate adenocarcinoma of low risk (30%), intermediate risk (49%) and high risk (21%) were included for adjuvant (34%) or salvage radiation therapy (66%) after radical prostatectomy (RP). All patients underwent radiotherapy with image-guided IMRT/VMAT to a total dose of 62.5 Gy in 2.5 Gy/fraction in 25 fractions. Sixteen patients (14%) received concomitant androgen deprivation therapy.With a median follow-up of 29 months (range 3-60 months) all patients but three are alive. Eleven patients (10%) developed exclusive biochemical relapse while 19 patients (17%) presented macroscopically visible relapse: prostatectomy bed in two patients (2%), pelvic lymph nodes in 13 patients (11.5%) and distant metastases in four patients (4%). The 3 years actuarial rates for OS, bFRS, and DMFS were 99.1, 91.1 and 91.2%, respectively. Acute and late tolerance was satisfactory. Maximal acute genitourinary (AGU) toxicity was G2 in 8% of patients; maximal acute gastrointestinal (AGI) toxicity was G2 in 3.5% of patients; maximal late genitourinary (LGU) toxicity was G3 in 1% of patients and maximal late gastrointestinal (LGI) toxicity was G2 in 2% of patients. There were no cases of severe acute or late toxicity. No relationship was found between acute or late GI/GU adverse effects and dosimetric parameters, age, presence of comorbidities or concomitant treatments.Hypofractionated radiotherapy (62.5 Gy in 25 2.5 Gy fractions) is feasible and well tolerated with low complication rates allowing for a moderate dose-escalation that offers encouraging clinical results for biochemical control and survival in patients with prostate cancer after radical prostatectomy.

Determining how the nervous system controls tendon-driven bodies remains an open question. Stochastic optimal control (SOC) has been proposed as a plausible analogy in the neuroscience community. SOC relies on solving the Hamilton-Jacobi-Bellman equation, which seeks to minimize a desired cost function for a given task with noisy controls. We evaluate and compare three SOC methodologies to produce tapping by a simulated planar 3-joint human index finger: iterative Linear Quadratic Gaussian (iLQG), Model-Predictive Path Integral Control (MPPI), and Deep Forward-Backward Stochastic Differential Equations (FBSDE). We show that averaged over 128 repeats these methodologies can place the fingertip at the desired final joint angles but–because of kinematic redundancy and the presence of noise–they each have joint trajectories and final postures with different means and variances. iLQG in particular, had the largest kinematic variance and departure from the final desired joint angles. We demonstrate that MPPI and FBSDE have superior performance for such nonlinear, tendon-driven systems with noisy controls.Clinical relevance— The mathematical framework provided by MPPI and FBSDE may be best suited for tendon-driven anthropomorphic robots, exoskeletons, and prostheses for amputees.

Variability in muscle force is a hallmark of healthy and pathological human behavior. Predominant theories of sensorimotor control assume ‘motor noise’ leads to force variability and its ‘signal dependence’ (variability in muscle force whose amplitude increases with intensity of neural drive). Here, we demonstrate that the two proposed mechanisms for motor noise (i.e. the stochastic nature of motor unit discharge and unfused tetanic contraction) cannot account for the majority of force variability nor for its signal dependence. We do so by considering three previously underappreciated but physiologically important features of a population of motor units: 1) fusion of motor unit twitches, 2) coupling among motoneuron discharge rate, cross-bridge dynamics, and muscle mechanics, and 3) a series-elastic element to account for the aponeurosis and tendon. These results argue strongly against the idea that force variability and the resulting kinematic variability are generated primarily by ‘motor noise.’ Rather, they underscore the importance of variability arising from properties of control strategies embodied through distributed sensorimotor systems. As such, our study provides a critical path toward developing theories and models of sensorimotor control that provide a physiologically valid and clinically useful understanding of healthy and pathologic force variability., Author summary Variability in our movements is thought to arise predominantly from ‘noise’ in the processes that convert central neural drive into muscle force. Constant variance of such noise has been a theoretical basis from which to explain various aspects of motor behavior. However, the physiological basis for such an assumption has not been tested rigorously. Our new computational model of a population of motor units demonstrates that non-physiological assumptions in previous models have led to erroneous interpretations of the role and significance of motor unit properties in the generation of force variability. Our results provide a clear path forward for future efforts using computational modeling to build theories of how altered neuromuscular systems emerge in aging or neurological disorders.

Objective: Interest in low-dose radiotherapy (LD-RT) for the symptomatic treatment of nonmalignant conditions, including inflammatory and degenerative disorders of the joints and para-articular soft tissues, has increased substantially in recent years. In the present document, we provide a CT-based contouring atlas to help identify and delineate the most common osteoarticular regions susceptible to LD-RT. Methods: The clinical efficacy of LD-RT is supported by a large body of evidence. However, there is no consensus on the parameters for contouring the planning target volume (PTV). Moreover, 3D simulation and planning should be the standard of care even for nonmalignant disorders. For this reason, the present guidelines were prepared to help guide PTV contouring based on CT images, with the same quality criteria for patient immobilization, treatment simulation, planning and delivery as those routinely applied for cancer radiotherapy. Results: PTV for radiotherapy requires precise identification of the target areas based on CT and other imaging techniques. Using a series of cases treated at our institution, we have defined the PTVs for each location on the simulation CT to establish the relationship between the image and the anatomical structures to be treated. We also specify the immobilization systems used to ensure treatment accuracy and reproducibility. Conclusions: This comprehensive atlas based on CT images may be of value to radiation oncologists who wish to use LD-RT for the symptomatic treatment of degenerative or inflammatory osteoarticular diseases. Advances in knowledge: The recommendations and contouring atlas described in this article provide an eminently practical tool for LD-RT in non-malignant conditions, based on the same quality criteria recommended for all modern radiotherapy treatments in Spain.

Coherence analysis has the ability to identify the presence of common descending drive shared by motor unit pools and reveals its spectral properties. However, the link between spectral properties of shared neural drive and functional interactions among muscles remains unclear. We assessed shared neural drive between muscles of the thumb and index finger while participants executed two mechanically distinct precision pinch tasks, each requiring distinct functional coordination among muscles. We found that shared neural drive was systematically reduced or enhanced at specific frequencies of interest (~10 and ~40 Hz). While amplitude correlations between surface EMG signals also exhibited changes across tasks, only their coherence has strong physiological underpinnings indicative of neural binding. Our results support the use of intermuscular coherence as a tool to detect when coactivated muscles are members of a functional group or synergy of neural origin. Furthermore, our results demonstrate the advantages of considering neural binding at 10, ~20, and >30 Hz, as indicators of task-dependent neural coordination strategies. NEW & NOTEWORTHY It is often unclear whether correlated activity among muscles reflects their neural binding or simply reflects the constraints defining the task. Using the fact that high-frequency coherence between EMG signals (>6 Hz) is thought to reflect shared neural drive, we demonstrate that coherence analysis can reveal the neural origin of distinct muscle coordination patterns required by different tasks.

To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40–62 Gy were delivered in 5–10 fractions. Surgery was performed after SBRT and restaging. Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0–1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6–59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.

As button batteries have become worldwide used, there have been an increase in its ingest cases, mostly in pediatric population. Also, it is in this group where most complications and death cases are presented according to latest publications. In Colombia there are not public programs that pursuit to prevent the ingestion of this kind of foreign body. We report our experience in the management of these patients in a pediatric hospital.We performed a retrospective review of cases where patients attend to the emergency room for suspected foreign body ingestion between January 2007 and December 2015. In a total of 46 cases the foreign body was a battery.85% where under 5 years old. 68% present symptoms. The most frequent location and with the worst complications was the esophagus. All patients that required ICU in the postoperative period where also in that group. There was one case of mortality.There must be an education plan for health personal and general population regarding the danger that represent button batteries at the reach of children, and the urgency that implies its attention once an ingestion has occurred. It is important to establish protocols in each institution for an appropriate and urgent extraction.Con la popularización del uso de pilas de botón se ha visto una tendencia al aumento en los casos de ingesta de estas, principalmente en la población pediátrica. Además, es en esta población en donde las mayores secuelas se presentan y en la que se ubican la mayoría de los casos de mortalidad publicados en estudios internacionales. En Colombia, aún no se disponen de estadísticas completas al respecto. No se tiene una cultura ni políticas de prevención de ingesta de este tipo de cuerpos extraños. En este trabajo reportamos nuestra experiencia en el manejo de estos pacientes.Se realizó una revisión retrospectiva de los casos de pacientes que consultaron por sospecha de ingesta de cuerpos extraños desde enero de 2007 hasta diciembre de 2015. Se obtuvieron 46 casos que correspondían a ingesta de pilas.El 85% eran pacientes menores de 5 años y el 68% presentaba algún síntoma previo al ingreso. La localización más frecuente y con mayor morbilidad fue el esófago. Todos los pacientes que requirieron UCI (Unidad de Cuidados Intensivos) post-extracción pertenecían a ese grupo. Hubo un caso de mortalidad relacionado.Se debe educar a la población y al personal en salud respecto al peligro que representa que las pilas de botón estén al alcance de los niños y la urgencia que debe tener su atención una vez se ha ingerido este cuerpo extraño. Es importante establecer protocolos de manejo en las instituciones para lograr la extracción de estos dispositivos de manera urgente.

The total hip arthroplasty with short stems to preserve bone is a good choice in young patients that expected future revision surgery, it is also a good choice when we use approaches for minimal invasive surgeries. In this study, we have evaluated, clinically and radiologically, our experience in total hip arthroplasty with the use of short stems and metaphyseal anchorage. In total we have involved 23 patients with a mean age of 50.2 years (range 45 to 69 y/o) at the time of surgery. The median follow-up was greater than five years. There was a slight Varus femoral stem in three cases, one of them in severe varus. The latter presented continuous pain in the lateral aspect of the thigh that increased with time, with a diaphyseal reaction and an increase in radiolucencies around the stem that required revision surgery 12 months postoperative. A longer follow-up is required to analyze the results and confirm the durability of the observed clinical findings. Patients were evaluated radiological and clinically using the scale of Merle dAubigné (MD).La artroplastía total de cadera con los vástagos cortos encaminada a preservar el hueso es una buena opción en pacientes jóvenes a quienes se les prevé futuras cirugías de revisión. También es una buena elección cuando se utilizan cirugías con abordajes miniinvasivos. En este estudio clínico y radiológico hemos evaluado nuestra experiencia en el uso de artroplastía total de cadera con vástagos cortos de anclaje metafisario tipo DePuy Próxima. En total se han intervenido 23 pacientes con una edad media de 50.2 años (rango de 45 a 69 años) en el momento de la cirugía. El seguimiento medio fue de más de cinco años. Hubo un ligero varo del tallo femoral en tres casos, uno de ellos en varo severo. Este último caso presentó dolor continuo en las caras laterales del muslo que aumentó con el tiempo junto con una reacción diafisaria y un aumento en el tallo que requirió cirugía de revisión a los 12 meses postoperatorios. Se requiere un seguimiento más prolongado para analizar los resultados y confirmar la durabilidad de los resultados clínicos observados. Los pacientes fueron evaluados radiológica y clínicamente utilizando el baremo de Merle dAubigné (MD).

Tendon-driven systems have many benefits over other actuation strategies such as torque-driven systems; however, their over-determined nature and posture-dependent actuation presents strong constraints on their control. Also, parameters or even exact structure of the model in these systems, especially in the biological ones, are normally not clear to the controller. Here, we propose a modified Genetic Algorithm that provides the tendon excursion values for the limb to follow a desired trajectory. Our results show that the proposed algorithm was able to accurately follow the desired trajectory without the model of the system being exposed to it. We believe that this method can enable biologically inspired tendon-driven mechanisms with variable mechanical structures to autonomously control their movements.

Personalized training by taking into account individual anatomy to improve performance is a research frontier. In this paper, we first introduce an analytical method to study the pattern of changes in muscle forces as a function of posture. Our method is also able to analyze variation of maximal muscle force and muscle activation values (in various postures) as a result of posture-dependent changes in moment arms. This method also helps us evaluate the utility of person specific training. It also provides us with model based approximations for activation and muscle force patterns during different motions without a need for subject recordings, which enables athletes to have a better understanding of how each muscle contributes during each posture, in a fast and efficient way. Second, we analyze the results of this method for a simple squat move. Our results show that both maximal muscle force and muscle activation values have variable sensitivity to the moment arm values for different postures and muscles. It suggests that individually modified training plans could likely improve performance for some sets of movements.

Study design Review paper. Introduction Hand dexterity is multifaceted and essential to the performance of daily tasks. Timed performance and precision demands are the most common features of quantitative dexterity testing. Measurement concepts such as rate of completion, in-hand manipulation and dynamic force control of instabilities are being integrated into assessment tools for the pediatric population. Purpose To review measurement concepts inherent in pediatric dexterity testing and introduce concepts that are infrequently measured or novel as exemplified with two assessment tools. Methods Measurement concepts included in common assessment tools are introduced first. We then describe seldom measured and novel concepts embedded in two instruments; the Functional Dexterity Test (FDT) and the Strength–Dexterity (SD) Test. Discussion The inclusion of novel yet informative tools and measurement concepts in our assessments could aid our understanding of atypical dexterity, and potentially contribute to the design of targeted therapy programs.

Study design Retrospective Cohort Introduction Important outcomes of polliciation to treat thumb hypoplasia/aplasia include strength, function, dexterity, and quality of life. Purpose of the Study To evaluate outcomes and examine predictors of outcome after early childhood pollicization. Methods 8 children (10 hands) were evaluated 3–15 years after surgery. Physical examination, questionnaires, grip and pinch strength, Box and Blocks, 9-hole pegboard, and strength-dexterity (S-D) tests were performed. Results Pollicized hands had poor strength and performance on functional tests. Six of 10 pollicized hands had normal dexterity scores but less stability in maintaining a steady-state force. Predictors of poorer outcomes included older age at surgery, reduced metacarpophalangeal and interphalangeal range of motion, and radial absence. Discussion Pollicization resulted in poor strength and overall function, but normal dexterity was often achieved using altered control strategies. Conclusions Most children should obtain adequate dexterity despite weakness after pollicization except older or severely involved children. Level of evidence IV

Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model. The closed-loop simulation included a musculotendon model, muscle spindle, Golgi tendon organ (GTO), and a tracking controller which enabled target-guided force tracking. We demonstrate that closed-loop control of an afferented musculotendon suffices to replicate and explain surprisingly many cardinal features of involuntary force variability. Specifically, we present 1) a potential origin of low-frequency force variability associated with co-modulation of motor unit firing rates (i.e.,‘common drive’), 2) an in-depth characterization of how proprioceptive feedback pathways suffice to generate 5-12 Hz physiological tremor, and 3) evidence that modulation of those feedback pathways (i.e., presynaptic inhibition of Ia and Ib afferents, and spindle sensitivity via fusimotor drive) influence the full spectrum of force variability. These results highlight the previously underestimated importance of closed-loop neuromechanical interactions in explaining involuntary force variability during voluntary ‘isometric’ force control. Furthermore, these results provide the basis for a unifying theory that relates spinal circuitry to various manifestations of altered involuntary force variability in fatigue, aging and neurological disease., Author summary Involuntary fluctuations in muscle force are an unavoidable consequence of human motor control and underlie movement execution errors. Amplification and distortion of involuntary force variability are common phenomena found in various neurological conditions and in fatigue. However, the underlying mechanisms for this are often unclear. We investigated the generation and modulation of involuntary force variability arising from different sources, as well as their interactions. We used a closed-loop simulation which included a physiologically-grounded model of an afferented musculotendon and an error-controller. We show that interactions among neural noise, musculotendon mechanics, proprioceptive feedback, and error correction are critical components of force control, and by taking these into account, our model was able to both replicate and explain many cardinal features of involuntary force variability previously reported experimentally. Also, our results suggest previously unrecognized pathways through which force variability may be altered in fatigue and in certain neurological diseases. Finally, we emphasize the potential for important clinical and scientific information to be extracted from relatively simple, non-invasive measurements of force.

Dexterity after finger pollicization (reconstruction to thumb) is critical to functional outcomes. While most tests of hand function evaluate a combination of strength, coordination, and motor control, the Strength-Dexterity (S-D) paradigm focuses on the dynamic control of fingertip forces. We evaluated 10 pollicized and 5 non-pollicized hands from 8 participants ages 4-17 years (2 female, 6 male; 10.6 ± 4.5 years). Participants partially compressed and held an instrumented spring prone to buckling between the thumb and first finger to quantify dynamic control over the direction and magnitude of fingertip forces. They also completed traditional functional tests including grip, lateral pinch, and tripod pinch strength, Box and Blocks, and 9-hole peg test. Six of 10 pollicized hands and all non-pollicized hands had S-D scores comparable to typically developing children. However, dynamical analysis showed that pollicized hands exhibit greater variability in compression force, indicating poorer corrective action. Almost all pollicized hands scored below the normal range for the traditional functional tests. The S-D test Z-scores correlated moderately with Z-scores from the other functional tests (r = 0.54-0.61; p = 0.02-0.04) but more weakly than amongst the other functional measures (r = 0.58-0.83; p = 0.0002-0.02), suggesting that the S-D test captures a different domain of function. A higher incidence of radial absence in the hands with poor S-D scores (3/4 vs. 0/6 in hands with normal S-D scores, p = 0.03) was the only clinical characteristic associated with S-D outcome. Overall, these results suggest that while most pollicized hands can control fingertip forces, the nature of that control is altered.

For young adults, balance is essential for participation in physical activities but is often disrupted following lower extremity injury. Clinical outcome measures such as single limb balance (SLB), Y-balance (YBT), and the single limb hop and balance (SLHB) tests are commonly used to quantify balance ability following injury. Given the varying demands across tasks, it is likely that such outcome measures provide useful, although task-specific, information. But the extent to which they are independent and contribute to understanding the multiple contributors to balance is not clear. Therefore, the purpose of this study was to investigate the associations among these measures as they relate to the different contributors to balance. Thirty-seven recreationally active young adults completed measures including Vertical Jump, YBT, SLB, SLHB, and the new Lower Extremity Dexterity test. Principal components analysis revealed that these outcome measures could be thought of as quantifying the strength, multijoint coordination, and sensorimotor processing contributors to balance. Our results challenge the practice of using a single outcome measure to quantify the naturally multidimensional mechanisms for everyday functions such as balance. This multidimensional approach to, and interpretation of, multiple contributors to balance may lead to more effective, specialized training and rehabilitation regimens.

Electrocardiogram (ECoG) recordings are very attractive for Brain Machine Interface (BMI) applications due to their balance between good signal to noise ratio and minimal invasiveness. The design of ECoG signal decoders is an open research area to date which requires a better understanding of the nature of these signals and how information is encoded in them. In this study, a linear and a non-linear method, Linear Regression Model (LRM) and Artificial Neural Network (ANN) respectively, were used to decode finger movements from energy in band-specific ECoG signals. It is shown that the ANN only slightly outperformed the LRM, which suggests that finger movements are mainly represented by a linear transformation of energy in band-specific ECoG signals. In addition, comparing our results to similar Electroencephalogram (EEG) studies illustrated that the spatio-temporal summation of multiple neural signals is itself linearly correlated with movement, and is not an artifact introduced by the scalp or cranium. Furthermore, a new algorithm was employed to reduce the number of spectral features of the input signals required for either of the decoding methods.

Biological and robotic grasp and manipulation are undeniably similar at the level of mechanical task performance. However, their underlying fundamental biological vs. engineering mechanisms are, by definition, dramatically different and can even be antithetical. Even our approach to each is diametrically opposite: inductive science for the study of biological systems vs. engineering synthesis for the design and construction of robotic systems. The past 20 years have seen several conceptual advances in both fields and the quest to unify them. Chief among them is the reluctant recognition that their underlying fundamental mechanisms may actually share limited common ground, while exhibiting many fundamental differences. This recognition is particularly liberating because it allows us to resolve and move beyond multiple paradoxes and contradictions that arose from the initial reasonable assumption of a large common ground. Here, we begin by introducing the perspective of neuromechanics, which emphasizes that real-world behavior emerges from the intimate interactions among the physical structure of the system, the mechanical requirements of a task, the feasible neural control actions to produce it, and the ability of the neuromuscular system to adapt through interactions with the environment. This allows us to articulate a succinct overview of a few salient conceptual paradoxes and contradictions regarding under-determined vs. over-determined mechanics, under- vs. over-actuated control, prescribed vs. emergent function, learning vs. implementation vs. adaptation, prescriptive vs. descriptive synergies, and optimal vs. habitual performance. We conclude by presenting open questions and suggesting directions for future research. We hope this frank and open-minded assessment of the state-of-the-art will encourage and guide these communities to continue to interact and make progress in these important areas at the interface of neuromechanics, neuroscience, rehabilitation and robotics.

The purpose of this study was to evaluate the effectiveness of the new Double-V osteotomy of the first metatarsophalangeal joint (1stMPJ) in patients with hallux limitus (HL). A study of 66 patients was performed, 33 patients were treated Cheilectomy and 33 were treated Double-V. All patients underwent an assessment of the passive mobility of the 1stMPJ before the procedure, reevaluated 12 months later evaluating dorsiflexion, plantarflexion, and patients status using both the American Orthopaedic Foot and Ankle Society (AOFAS) for Hallux Metatarsophalangeal–Interphalangeal Scale. In comparing the improvement achieved regarding the increase of mobility obtained with surgical treatment, the feet operated with procedure Double-V gained significant degrees of movement increased in all analyzed parameters (P

We studied whether the time-varying forces that control unstable foot-ground interactions provide insight into the neural control of dynamic leg function. Twenty elite (10F, 26.4±3.5yrs) and 20 recreational (10F, 24.8±2.4yrs) athletes used an isolated leg to maximally compress a slender spring designed to buckle at low forces while seated. The foot forces during the compression at the edge of instability quantify the maximal sensorimotor ability to control dynamic foot-ground interactions. Using the nonlinear analysis technique of attractor reconstruction, we characterized the spatial (interquartile range IQR) and geometric (trajectory length TL, volume V, and sum of edge lengths SE) features of the dynamical behavior of those force time series. ANOVA confirmed the already published effect of sex, and a new effect of athletic ability, respectively, in TL (p=0.014 and p

Working memory is a crucial ability we use in daily life. However, the cellular mechanisms supporting working memory still remain largely unclear. A key component of working memory is persistent neural firing which is believed to serve short-term (hundreds of milliseconds up to tens of seconds) maintenance of necessary information. In this review, we will focus on the role of transient receptor potential canonical (TRPC) channels as a mechanism underlying persistent firing. Many years of in vitro work have been suggesting a crucial role of TRPC channels in working memory and temporal association tasks. If TRPC channels are indeed a central mechanism for working memory, manipulations which impair or facilitate working memory should have a similar effect on TRPC channel modulation. However, modulations of working memory and TRPC channels were never systematically compared, and it remains unanswered whether TRPC channels indeed contribute to working memory in vivo or not. In this article, we review the effects of G-protein coupled receptors (GPCR) and neuromodulators, including acetylcholine, noradrenalin, serotonin and dopamine, on working memory and TRPC channels. Based on comparisons, we argue that GPCR and downstream signaling pathways that activate TRPC, generally support working memory, while those that suppress TRPC channels impair it. However, depending on the channel types, areas, and systems tested, this is not the case in all studies. Further work to clarify involvement of specific TRPC channels in working memory tasks and how they are affected by neuromodulators is still necessary in the future.

To analyze the efficacy and safety of a new preoperative intensity-modulated radiotherapy (IMRT) and integrated-boost chemoradiation scheme. In all, 74 patients were treated with IMRT and concurrent standard dose capecitabine. The dose of the planning target volume (PTV) encompassing the tumor, mesorectum, and pelvic lymph nodes was 46 Gy in 23 fractions; the boost PTV, at a dose of 57.5 Gy in 23 fractions, included the macroscopic primary tumor and pathological lymph nodes. The patients underwent surgery 6–8 weeks after chemoradiation. The complete treatment data of 72 patients were analyzed. Tumor downstaging was achieved in 55 patients (76.38 %) and node downstaging in 34 (47.2 %). In 22 patients (30.6 %), there was complete pathological response (ypCR). The circumferential resection margin was free of tumor in 70 patients (97.2 %). The 3-year estimated overall survival and disease-free survival rates were 95.4 and 85.9 % respectively, and no local relapse was found; however, ten patients (13.8 %) developed distant metastases. High pathologic tumor (pT) downstaging was shown as a favorable prognostic factor for disease-free survival. No grade 4 acute radiotherapy-related toxicity was found. The IMRT and integrated-boost chemoradiation scheme offered higher rates of ypCR and pT downstaging, without a significant increase in toxicity. The circumferential margins were free of tumors in the majority of patients. Primary tumor regression was associated with better disease-free survival.

The worsening of fine motor skills for manipulation, whereas not a health risk in the elderly people like loss of strength (1) and risk of falls (2), is nevertheless a critical and little understood contributor to the decline of quality of life, social participation, and work capabilities (3). Pick-and-place standardized tests of dexterity (4–6) reveal behavioral impairments in upper extremity and hand function after the age of 65 (7) and have been of some clinical utility. These methods, however, lack the specificity and resolution to quantify in detail the dynamic control of fingertip force vectors that is so critical to dexterous manipulation. Given this unmet need, we developed the strength–dexterity (SD) test to measure dynamic dexterous manipulation, which we define as the dynamic regulation of fingertip force vector magnitude and direction. It is based on the mechanical perspective of evaluating the dynamical ability of the fingertips to stabilize unstable objects (8–14). This simple test consists of measuring a person’s ability to compress slender springs with the fingertips. The physical characteristics of each spring define how stiff, compliant, stable, and prone to buckling it is. As such, the SD test has been shown to assess the interactions among sensory, motor, and neural processing capabilities in the behavioral context of dexterous manipulation (9,11,12,14). The SD test differs from available tests of static forces and pick-and-place tasks in important ways (see Discussion section). For example, the Nine Hole Peg test (4) measures the time it takes to pick up, insert into holes, and remove nine pegs. Given that it studies the use of the whole upper extremity to grasp and orient rigid objects, an individual can apply excessive forces or adapt their kinematic trajectories to achieve the same score, and the directional control of the fingertips forces is not measured in detail. Using the SD test to quantify dynamic dexterous manipulation is also relevant to fine manipulation in activities of daily living. The dynamic control of fingertip force vector magnitude and direction is important functionally for manipulating fragile, deformable, or small objects in daily life. Basic research studies have shown that when older people are asked to produce static fingertip forces against a rigid surface, they tend to misdirect (15) the force vector and fail to precisely regulate its magnitude (16,17), especially at low magnitudes (17). This has been attributed to differential weakening of hand musculature or changes in the neural coupling among muscles (18). Such deficits in the control of static fingertip force vectors could compromise force and moment balance of the object being manipulated (19). However, these directional deficits are not observed or implicated consistently (20,21)—and even if present, it is unclear whether and how they would affect dynamic manipulation of hand-held objects. Here we extend those studies of static force regulation and pick-and-place tasks by quantifying the dynamical control of fingertip force vector magnitude and direction in middle-aged and older adults.

Background Squamous cell carcinoma (SCC) in the ungual apparatus is a rare neoplasia. Although it is the most prevalent malignant tumour in this region, its diagnosis is often delayed because it is likened to benign or infectious processes. Objectives Present a case of SCC with subungual location in a toe, and carry out a review of the literature in relation to the most important aspects of subungual SCC in toes. Methods We describe the case of a white woman aged 72, with SCC located in the pulp and in the distal area of the nail bed of the third toe, associated with subungual exostosis. The literature on SCC in the subungual area of toes, in all its forms under clinical or histopathological presentation, is reviewed by means of a search involving Medline, PubMed, and Google Academic, from January 1994 to December 2011. Results Only 36 cases of subungual SCC in toes were reported in the 18 years that were reviewed. The average age of cases reviewed was 58.92, and the male-to-female ratio was 2 : 1. The most affected toe is the hallux, in 69.4% of cases. In 50% of cases, aetiology is unknown or indeterminate; in 22.3% of cases, aetiology is metastatic; and in 19.5% of cases, it is associated with human papillomavirus (HPV). In 58.2% of cases, partial or total resection of the distal phalanx was carried out, of the entire toe, or of the osseous ray of the foot. Conclusions Chronic tissue irritation caused by microtrauma associated with subungual exostosis is the most probable aetiology of the case presented.

While it is clear that the development of dexterous manipulation in children exhibits dramatic improvements over an extended period, it is difficult to separate musculoskeletal from neural contributors to these important functional gains. This is in part due to the inability of current methods to disambiguate improvements in hand strength from gains in finger dexterity (i.e., the dynamic control of fingertip force vectors at low magnitudes). We adapted our novel instrumentation to evaluate finger dexterity in 130 typically developing children between the ages of 4 and 16 yr. We find that finger dexterity continues to develop well into late adolescence and musculoskeletal growth and strength are poorly correlated with the improvements in dexterity. Importantly, because these behavioral results seem to mirror the known timelines of neuroanatomical development up to adolescence, we speculate that they reflect the functional benefits of such continual neural maturation. This novel perspective now enables the systematic study of the functional roles of specific neuroanatomical structures and their connectivity, maturity, and plasticity. Moreover, the temporal dynamics of the fingertip force vectors shows improvements in stability that provide a novel way to look at the maturation of finger control. From a clinical perspective, our results provide a practical means to chart functional development of dexterous manipulation in typically developing children and could be adapted for clinical use and for use in children with developmental disorders.

Developmental improvements in dynamic manipulation abilities are typically attributed to neural maturation, such as myelination of corticospinal pathways, neuronal pruning, and synaptogenesis. However the contributions from changes in the peripheral motor system are less well understood. Here we investigated whether there are developmental changes in muscle activation-contraction dynamics and whether these changes contribute to improvements in dynamic manipulation in humans. We compared pinch strength, dynamic manipulation ability, and contraction time of the first dorsal interosseous muscle in typically developing preadolescent, adolescent, and young adults. Both strength and dynamic manipulation ability increased with age (p< 0.0001 andp< 0.00001, respectively). Surprisingly, adults had a 33% lower muscle contraction time compared with preadolescents (p< 0.01), and contraction time showed a significant (p< 0.005) association with dynamic manipulation abilities. Whereas decreases in muscle contraction time during development have been reported in the animal literature, our finding, to our knowledge, is the first report of this phenomenon in humans and the first finding of its association with manipulation. Consequently, the changes in the muscle contractile properties could be an important complement to neural maturation in the development of dynamic manipulation. These findings have important implications for understanding central and peripheral contributors to deficits in manipulation in atypical development, such as in children with cerebral palsy.

We investigated how kinematic redundancy interacts with the neurophysiological control mechanisms required for smooth and accurate, rapid limb movements. Biomechanically speaking, tendon excursions are over-determined because the rotation of few joints determines the lengths and velocities of many muscles. But how different are the muscle velocity profiles induced by various, equally valid hand trajectories? We used an 18-muscle sagittal-plane arm model to calculate 100,000 feasible shoulder, elbow, and wrist joint rotations that produced valid basketball free throws with different hand trajectories, but identical initial and final hand positions and velocities. We found large differences in the eccentric and concentric muscle velocity profiles across many trajectories; even among similar trajectories. These differences have important consequences to their neural control because each trajectory will require unique, time-sensitive reflex modulation strategies. As Sherrington mentioned a century ago, failure to appropriately silence the stretch reflex of any one eccentrically contracting muscle will disrupt movement. Thus, trajectories that produce faster or more variable eccentric contractions will require more precise timing of reflex modulation across motoneuron pools; resulting in higher sensitivity to time delays, muscle mechanics, excitation/contraction dynamics, noise, errors and perturbations. By combining fundamental concepts of biomechanics and neuroscience, we propose that kinematic and muscle redundancy are, in fact, severely limited by the need to regulate reflex mechanisms in a task-specific and time-critical way. This in turn has important consequences to the learning and execution of accurate, smooth and repeatable movements-and to the rehabilitation of everyday limb movements in developmental and neurological conditions, and stroke.

Objective We studied the fundamentals of muscle afferentation by building a Neuro-mechano-morphic system actuating a cadaveric finger. This system is a faithful implementation of the stretch reflex circuitry. It allowed the systematic exploration of the effects of different fusimotor drives to the muscle spindle on the closed-loop stretch reflex response. Approach As in Part I of this work, sensory neurons conveyed proprioceptive information from muscle spindles (with static and dynamic fusimotor drive) to populations of α-motor neurons (with recruitment and rate coding properties). The motor commands were transformed into tendon forces by a Hill-type muscle model (with activation-contraction dynamics) via brushless DC motors. Two independent afferented muscles emulated the forces of flexor digitorum profundus and the extensor indicis proprius muscles, forming an antagonist pair at the metacarpophalangeal joint of a cadaveric index finger. We measured the physical response to repetitions of bi-directional ramp-and-hold rotational perturbations for 81 combinations of static and dynamic fusimotor drives, across four ramp velocities, and three levels of constant cortical drive to the α-motor neuron pool. Main results We found that this system produced responses compatible with the physiological literature. Fusimotor and cortical drives had nonlinear effects on the reflex forces. In particular, only cortical drive affected the sensitivity of reflex forces to static fusimotor drive. In contrast, both static fusimotor and cortical drives reduced the sensitivity to dynamic fusimotor drive. Interestingly, realistic signal-dependent motor noise emerged naturally in our system without having been explicitly modeled. Significance We demonstrate that these fundamental features of spinal afferentation sufficed to produce muscle function. As such, our Neuro-mechano-morphic system is a viable platform to study the spinal mechanisms for healthy muscle function-and its pathologies such as dystonia and spasticity. In addition, it is a working prototype of a robust biomorphic controller for compliant robotic limbs and exoskeletons.

[Background]: Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution. [Objectives]: We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours. [Methods]: Seventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC. [Results]: miR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. [Conclusions]: miR-205 and miR-203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR-205 and miR-203 as prognostic markers in CSCC., J.P.-L. was partially supported by FEDER and MICINN (PLE2009-119, SAF2014-56989-R), Instituto de Salud Carlos III (PI07/0057, PI10/00328, PIE14/00066), Junta de Castilla y Leon (SA078A09, CSI034U13, CSI001U16), the ‘Eugenio Rodriguez Pascual’, the ‘Fundacion Inbiomed’ (Instituto Oncologico Obra Social de la Caja Guipozcoa-San Sebastian, Kutxa), IBSAL (IBY15/00003) and the ‘Fundacion Sandra Ibarra de Solidaridad frente al Cancer’. C.R.-C. is funded by Q3718001E (2009–2010) y GRS 612/A/11 (2011–2012) and the ‘Fundacion Eugenio Rodriguez Pascual’. A.C.-M. was supported by FIS (PI07/0057) and MICINN (PLE2009-119). J.H.M. was supported by the National Institutes of Health, a National Cancer Institute grant (R01 CA116481) and the Low-Dose Scientific Focus Area, Office of Biological & Environmental Research, U.S. Department of Energy (DE-AC02-05CH11231). J.C. was partially supported by Gerencia Regional de Salud (Junta de Castilla y Leon), GRS 1342 / A / 16.

Comparing the efficacy of alternative therapeutic strategies for the rehabilitation of motor function in chronically impaired individuals is often inconclusive. For example, a recent randomized clinical trial (RCT) compared robot-assisted vs. conventional therapy in 77 patients who had had chronic motor impairment after a cerebrovascular accident. While patients assigned to robotic therapy had greater improvements in the primary outcome measure (change in score on the upper extremity section of the Fugl-Meyer assessment), the absolute difference between therapies was small, which left the clinical relevance in question. Here we revisit that study to test whether the multidimensional rehabilitative response of these patients can better distinguish between treatment outcomes. We used principal components analysis to find the correlation of changes across seven outcome measures between the start and end of 8 weeks of therapy. Permutation tests verified the robustness of the principal components found. Each therapy in fact produces different rehabilitative trends of recovery across the clinical, functional, and quality of life domains. A rehabilitative trend is a principal component that quantifies the correlations among changes in outcomes with each therapy. These findings challenge the traditional emphasis of RCTs on using a single primary outcome measure to compare rehabilitative responses that are naturally multidimensional. This alternative approach to, and interpretation of, the results of RCTs may will lead to more effective therapies targeted for the multidimensional mechanisms of recovery. ClinicalTrials.gov number NCT00719433 . Registered July 17, 2008.

To analyse the predictive utility of penile colour Doppler ultrasonography after the injection of vasoactive agents for recovering erectile function after radical prostatectomy.A retrospective study was conducted on patients with erectile dysfunction after radical prostatectomy who were treated with intracavernous injections of prostaglandins E1 between January 1, 2006 and December 31, 2012. The study included patients with no history of erectile dysfunction prior to the surgery and who did not respond to medical treatment. Colour Doppler was performed on all patients after the intracavernous injection. A peak systolic velocity ≥30cm/sec and an end diastolic velocity ≤5cm/sec were considered normal haemodynamic values. We assessed the result of the treatment during the follow-up using the International Index of Erectile Function-5.We included 197 patients. The mean age was 60.8 (±6.3). The pathological diagnosis for all patients was adenocarcinoma, 74.1% of which were confined to the organ (T1-T2/Nx-N0). Treatment with injections after the surgery was started after a mean duration of 6.8 months (+3.5). The Doppler ultrasonography results were normal for 53 patients (26.9%). During the follow-up, 113 patients (57.4%) maintained functional erections; 55 of these patients (28%) did not require injections. Normal Doppler ultrasonography results were associated with a favourable response to treatment (p.01).The prostaglandin E1 test will help provide a diagnosis in erectile dysfunction for patients who have undergone prostatectomies. The test helps provide information on the vascular condition of the penis and useful prognostic information for the follow-up of these patients.

Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies—correlated muscle activations—to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption—when available—can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms of learning, plasticity, versatility and pathology in neuromuscular systems., Author Summary The manner in which the nervous system coordinates the multiple muscles in the body is complex. It has been studied for decades, but a more full understanding is needed to enable the development of effective evaluation and treatment methods in disorders that cause neuromuscular disability such as cerebral palsy and stroke. In addition, the computational control of robots has and will continue to improve as the brain’s methods of muscular control are progressively reverse-engineered. Here, we study the capacity of arm muscles to regulate the stiffness of the hand for tasks such as using tools, stabilizing hand-held objects, and using doors. Using a simplified but generalizable model, we show that there will be necessary trade-offs in the functional capabilities of the limb if the nervous system chooses to control muscles in functional groups. This adds to our understanding of the consequences of different strategies to control muscles for real-world tasks with multiple and often competing demands. It enables future research and clinical experiments on the learning and execution of the multiple tasks of varying difficulty encountered in real life. It also sheds light on the design of control strategies for robots to operate in human and unstructured environments.

We used a novel apparatus with three hinged finger pads to characterize collaborative multifinger interactions during dynamic manipulation requiring individuated control of fingertip motions and forces. Subjects placed the thumb, index, and middle fingertips on each hinged finger pad and held it—unsupported—with constant total grasp force while voluntarily oscillating the thumb's pad. This task combines the need to 1) hold the object against gravity while 2) dynamically reconfiguring the grasp. Fingertip force variability in this combined motion and force task exhibited strong synchrony among normal (i.e., grasp) forces. Mechanical analysis and simulation show that such synchronous variability is unnecessary and cannot be explained solely by signal-dependent noise. Surprisingly, such variability also pervaded control tasks requiring different individuated fingertip motions and forces, but not tasks without finger individuation such as static grasp. These results critically extend notions of finger force variability by exposing and quantifying a pervasive challenge to dynamic multifinger manipulation: the need for the neural controller to carefully and continuously overlay individuated finger actions over mechanically unnecessary synchronous interactions. This is compatible with—and may explain—the phenomenology of strong coupling of hand muscles when this delicate balance is not yet developed, as in early childhood, or when disrupted, as in brain injury. We conclude that the control of healthy multifinger dynamic manipulation has barely enough neuromechanical degrees of freedom to meet the multiple demands of ecological tasks and critically depends on the continuous inhibition of synchronous grasp tendencies, which we speculate may be of vestigial evolutionary origin.

Computationally efficient modeling of complex neuromuscular systems for dynamics and control simulations often requires accurate analytical expressions for moment arms over the entire range of motion. Conventionally, polynomial expressions are regressed from experimental data. But these polynomial regressions can fail to extrapolate, may require large datasets to train, are not robust to noise, and often have numerous free parameters. We present a novel method that simultaneously estimates both the form and parameter values of arbitrary analytical expressions for tendon excursions and moment arms over the entire range of motion from sparse datasets. This symbolic regression method based on genetic programming has been shown to find the appropriate form of mathematical expressions that capture the physics of mechanical systems. We demonstrate this method by applying it to (i) experimental data from a physical tendon-driven robotic system with arbitrarily routed multiarticular tendons and (ii) synthetic data from musculoskeletal models. We show it outperforms polynomial regressions in the amount of training data, ability to extrapolate, robustness to noise, and representation containing fewer parameters – all critical to realistic and efficient computational modeling of complex musculoskeletal systems.

In the present paper, we review what is currently known about the effects of deafness on the developing human auditory system and ask: Without use, does the immature auditory system lose the ability to normally function and mature? Any change to the structure or function of the auditory pathways resulting from a lack of activity will have important implications for future use through an auditory prosthesis such as a cochlear implant. Data to date show that deafness in children arrests and disrupts normal auditory development. Multiple changes to the auditory pathways occur during the period of deafness with the extent and type of change being dependent upon the age and stage of auditory development at onset of deafness, the cause or type of deafness, and the length of time the immature auditory pathways are left without significant input. Structural changes to the auditory nerve, brainstem, and cortex have been described in animal models of deafness as well in humans who are deaf. Functional changes in deaf auditory pathways have been evaluated by using a cochlear implant to stimulate the auditory nerve with electrical pulses. Studies of electrically evoked activity in the immature deaf auditory system have demonstrated that auditory brainstem development is arrested and that thalamo-cortical areas are vulnerable to being taken over by other competitive inputs (cross-modal plasticity). Indeed, enhanced peripheral sight and detection of visual movement in congenitally deaf cats and adults have been linked to activity in specific areas of what would normally be auditory cortex. Cochlear implants can stimulate developmental plasticity in the auditory brainstem even after many years of deafness in childhood but changes in the auditory cortex are limited, at least in part, by the degree of reorganization which occurred during the period of deafness. Consequently, we must identify hearing loss rapidly (i.e., at birth for congenital deficits) and provide cochlear implants to appropriate candidates as soon as possible. Doing so has facilitated auditory development in the thalamo-cortex and allowed children who are deaf to perceive and use spoken language.

It is well-known that muscle redundancy grants the CNS numerous options to perform a task. Does muscle redundancy, however, allow sufficient robustness to compensate for loss or dysfunction of even a single muscle? Are all muscles equally redundant? We combined experimental and computational approaches to establish the limits of motor robustness for static force production. In computer- controlled cadaveric index fingers, we find that only a small subset (

Using the advances in computing power, software and hardware technologies, virtual reality (VR), and gaming applications have the potential to address clinical challenges for a range of disabilities. VR-based games can potentially provide the ability to assess and augment cognitive and motor rehabilitation under a range of stimulus conditions that are not easily controllable and quantifiable in the real world. This article discusses an approach for maximizing function and participation for those aging with and into a disability by combining task-specific training with advances in VR and gaming technologies to enable positive behavioral modifications for independence in the home and community. There is potential for the use of VR and game applications for rehabilitating, maintaining, and enhancing those processes that are affected by aging with and into disability, particularly the need to attain a balance in the interplay between sensorimotor function and cognitive demands and to reap the benefits of task-specific training and regular physical activity and exercise.

Moving our fingertips toward objects to produce well-directed forces immediately upon contact is fundamental to dexterous manipulation. This apparently simple motion-to-force transition in fact involves a time-critical, predictive switch in control strategy. Given that dexterous manipulation must accommodate multiple mechanical conditions, we investigated whether and how this transition adapts to task difficulty. Eight adults (19–39 yr) produced ramps of isometric vertical fingertip force against a rigid surface immediately following a tapping motion. By changing target surface friction and size, we defined an easier (sandpaper, 11 mm diam) versus a more difficult (polished steel, 5 mm diam) task. As in prior work, we assembled fine-wire electromyograms from all seven muscles of the index finger into a seven-dimensional vector defining the full muscle coordination pattern—and quantified its temporal evolution as its alignment with a reference coordination pattern vector for steady-state force production. As predicted by numerical optimizations to neuromuscular delays, our empirical and sigmoidal nonlinear regression analyses show that the coordination pattern transitions begin sooner for the more difficult tasks than for the easier tasks (∼120 ms, P < 0.02, and ∼115 ms, P < 0.015, respectively) and that the coordination pattern transition in alignment is well represented by a sigmoidal trend ( R^2 > 0.7 in most cases). Importantly, the force vector following contact had smaller directional error ( P < 0.02) for the more difficult task even though the transition in coordination pattern was less stereotypical and uniform than for the easier task. These adaptations of transition strategy to task difficulty are compatible with an optimization to counteract neuromuscular delays and noise to enable this fundamental element of dexterous manipulation.

We present a numerical exploration of contact transitions with the fingertip. When picking up objects our fingertips must make contact at specific locations, and—upon contact—maintain posture while producing well-directed force vectors. However, the joint torques for moving the fingertip towards a surface ( τ m ) are different from those for producing static force vectors ( τ f ). We previously described the neural control of such abrupt transitions in humans, and found that unavoidable errors arise because sensorimotor time delays and lags prevent an instantaneous switch between different torques. Here, we use numerical optimization on a finger model to reveal physical bounds for controlling such rapid contact transitions. Resembling human data, it is necessary to anticipatorily switch joint torques to τ f at about 30 ms before contact to minimize the initial misdirection of the fingertip force vector. This anticipatory strategy arises in our deterministic model from neuromuscular lags, and not from optimizing for robustness to noise/uncertainties. Importantly, the optimal solution also leads to a trade-off between the speed of force magnitude increase versus the accuracy of initial force direction. This is an alternative to prevailing theories that propose multiplicative noise in muscles as the driver of speed–accuracy trade-offs. We instead find that the speed–accuracy trade-off arises solely from neuromuscular lags. Finally, because our model intentionally uses idealized assumptions, its agreement with human data suggests that the biological system is controlled in a way that approaches the physical boundaries of performance.

Studies of the degrees of freedom and "synergies" in musculoskeletal systems rely critically on algorithms to estimate the "dimension" of kinematic or neural data. Linear algorithms such as principal component analysis (PCA) are the most popular. However, many biological data (or realistic experimental data) may be better represented by nonlinear sets than linear subspaces. We evaluate the performance of PCA and compare it to two nonlinear algorithms [Isomap and our novel pointwise dimension estimation (PD-E)] using synthetic and motion capture data from a robotic arm with known kinematic dimensions, as well as motion capture data from human hands. We find that PCA can lead to more accurate dimension estimates when considering additional properties of the PCA residuals, instead of the dominant method of using a threshold of variance captured. In contrast to the single integer dimension estimates of PCA and Isomap, PD-E provides a distribution and range of estimates of fractal dimension that identify the heterogeneous geometric structure in the experimental data. A strength of the PD-E method is that it associates a distribution of dimensions to the data. Since there is no a priori reason to assume that the sets of interest have a single dimension, these distributions incorporate more information than a single summary statistic. Our preliminary findings suggest that fewer than ten DOFs are involved in some hand motion tasks. Contrary to common opinion regarding fractal dimension methods, PD-E yielded reasonable results with reasonable amounts of data. Given the complex nature of experimental and biological data, we conclude that it is necessary and feasible to complement PCA with methods that take into consideration the nonlinear properties of biological systems for a more robust estimation of their DOFs.