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Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included. Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5–1 Gy on every other day up to a total dose of 3–6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course. With a median follow-up of 10.5 months (range 7.55–12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p

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.

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 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.

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.

Background Surgery remains to be the main therapeutic approach for retroperitoneal sarcomas (RPS) although evidence supports that complementary radiotherapy increases local-control and survival. We present a multidisciplinary management and experience of a tertiary cancer center in the treatment of RPS and analyze current evidence of radiotherapy efficacy. Patients and methods We retrospectively reviewed 19 patients with primary or relapsed RPS treated between November 2009 and October 2018. Multidisciplinary approach comprised complete resection in 15 patients (79%) achieving resection R0 in 11 patients (58%), R1 in 4 patients (21%) and R2 in 2 patients (10%). Seven patients (37%) underwent a preoperative radiation (PRORT), 10 patients (53%), post-operative radiation (PORT) and 2 patients (10%), received radiotherapy exclusively. Ten patients (53%) received adjuvant chemotherapy. Results With a median follow-up of 24 months (2–114 months), actuarial rates of loco-regional relapse free survival (LRFS) at 1, 2 and 3 years were 77%, 77% and 67%, respectively. Actuarial rates of distant-metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) at 1, 2 and 3 years were 100%, 100% and 80% for DMFS; 94%, 77% and 67% for DFS and 100%, 91% and 91% for OS, respectively. Only surgical margins (negative vs. positive) showed significance for 3y-LRFS: 100% vs. 34.3%, p = 0.018. Treatment tolerance was acceptable with no acute or late toxicity higher than grade 2. Conclusions Complementary radiotherapy appears to be useful and well tolerated for the multidisciplinary management of RPS. Presence of positive surgical margins seems to be the most relevant prognostic factor through the follow-up.

Conservative surgery in combination with local radiation therapy is considered a standard approach for soft tissue sarcomas (STS) leading to high local control rates and widely replacing the need for amputations. A close relationship exists between total radiation dose and local control probability. Combination of external beam radiotherapy and perioperative brachytherapy represents a moderate dose escalation that could contribute to improve local control. From May 2015 to October 2018, 23 patients with histologically proven STS of various locations were prospectively entered into a data registry of perioperative HDR brachytherapy (PoBT) combined with external beam radiotherapy (EBRT). Multidisciplinary treatment comprised wide surgical excision, PoBT (16.5 Gy delivered in 3 fractions of 5.5 Gy twice daily with a gap time of at least 6 h between fractions), and EBRT delivered either pre- or postoperatively (median dose 47 Gy, range 40–57.5 Gy) up to a total accumulated radiotherapy equivalent dose for tumor of 69.5 to 86.5 Gy (median, 76.1 Gy), representing a moderate total dose escalation over the 66 Gy traditionally used. With a median follow-up of 13.4 months (range, 1–35.4 months), 22 patients (96%) remain alive without evidence of local or distant recurrence, 1 patient (4%) is alive with local relapse, and no patient has died because of tumor progression. Treatment-related adverse effects were mild or moderate. No cases of grades 4–5 late toxicity have been observed during the follow-up period. HDR PoBT is safe, feasible, and well tolerated and allows for a moderate radiation dose escalation with acceptable rates of tumor control. Further follow-up is necessary to confirm impact on final outcomes.

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.

Background: Walking is a complex process that is highly automated and efficient. This knowledge is essential for the study of pathological gait. The amputation of lower limbs involves new biomechanical load and gait patterns, and injuries due to overload or disuse may occur. The objective of this study is to assess muscle activation as part of the gait in unilateral transtibial amputee patients with prosthesis, at different speeds and with different plantar supports. Method: Included in the sample were 25 people with amputation and 25 control participants. Muscle activation was evaluated in both groups by means of surface electromyography (EMG) under normal and altered conditions. Results: Control participants did not show statistically significant differences (p ˃ 0.05) between their muscle groups, irrespective of support and speed. However, people with amputation did show differences in muscle activity in the quadriceps, all of which occurred at the highest speeds, irrespective of support. In the analysis between groups, significant differences (p &lt, 0.05) were obtained between the leg of the amputee patient and the leg of the control participant, all of them in the quadriceps, and at speeds 3 and 4, regardless of the insole used. Conclusions: Participants with unilateral transtibial amputation carry out more quadriceps muscle activity during gait compared to the control group.

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.

State-of-the-art Optical Music Recognition (OMR) techniques follow an end-to-end or holistic approach, i.e., a sole stage for completely processing a single-staff section image and for retrieving the symbols that appear therein. Such recognition systems are characterized by not requiring an exact alignment between each staff and their corresponding labels, hence facilitating the creation and retrieval of labeled corpora. Most commonly, these approaches consider an agnostic music representation, which characterizes music symbols by their shape and height (vertical position in the staff). However, this double nature is ignored since, in the learning process, these two features are treated as a single symbol. This work aims to exploit this trademark that differentiates music notation from other similar domains, such as text, by introducing a novel end-to-end approach to solve the OMR task at a staff-line level. We consider two Convolutional Recurrent Neural Network (CRNN) schemes trained to simultaneously extract the shape and height information and to propose different policies for eventually merging them at the actual neural level. The results obtained for two corpora of monophonic early music manuscripts prove that our proposal significantly decreases the recognition error in figures ranging between 14.4% and 25.6% in the best-case scenarios when compared to the baseline considered. This research work was partially funded by the University of Alicante through project GRE19-04, by the “Programa I+D+i de la Generalitat Valenciana” through grant APOSTD/2020/256, and by the Spanish Ministerio de Universidades through grant FPU19/04957.

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.

Optical Music Recognition (OMR) is the research area that studies how to transcribe the content from music documents into a structured digital format. Within this field, techniques based on Deep Learning represent the current state of the art. Nevertheless, their use is constrained by the large amount of labeled data required, which constitutes a relevant issue when dealing with historical manuscripts. This drawback can be palliated by means of Data Augmentation (DA), which encompasses a series of strategies to increase data without the need of manual labeling new images. This work studies the applicability of specific DA techniques in the context of end-to-end staff-level OMR methods. More precisely, considering two corpora of historical music manuscripts, we applied different types of distortions to the music scores and assessed their contribution in an end-to-end system. Our results show that some transformations are much more appropriate than others, leading up to a \(34.5\%\) of relative improvement with respect to scenario without DA.

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

Multiple sclerosis (MS) is a neurodegenerative disease with a complex autoimmune component, and it has a high prevalence among middle-aged females. The manifestations of the disease range from episodic somatosensory dysfunction to progressive and permanent central nervous system (CNS) damage. Due to a high prevalence of psychiatric comorbidities and proven abnormalities in serotonin (5-HT) levels among MS patients, they are usually on drugs that modify the serotonergic system. Through a comprehensive literature review of studies published in the last 10 years related to 5-HT in MS and its therapeutic applications, we aimed to elucidate the mechanism behind the neurotransmitter (NT) levels' abnormalities. Most importantly, we endeavored to gather the most up-to-date information about the full therapeutic potential of agents acting on this system. We discovered that multiple processes cause low levels of 5-HT in MS patients. The varying levels of the availability of the 5-HT transporter (SERT) in the CNS decreasing overall tryptophan (TRP) levels, and diversion of the amino acid away from its synthetic pathway constitute some of those. Studies in animals have shown that 5-HT levels' elevations could cause immune-modulating effects and could probably slow down the disease progression rate. Human studies have shown a more diverse and complex response. Promising results have been obtained in the last 10 years regarding 5-HT's immune-modulatory role in MS patients and its therapeutic applications. Human studies with a larger population and feasible designs are still needed to fully ascertain the effects of serotonin on the immune system and disease progression in patients with MS.

Coronary artery disease (CAD) is a significant contributor to mortality in America. A common risk factor of CAD is hyperlipidemia. Treatment guidelines of hyperlipidemia are well established. Statins are the cornerstone of treating hyperlipidemia. New medications such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors) have also illustrated significant results in treating hyperlipidemia. While multiple studies exemplify the disparities in statin and PCSK9 inhibitors utilization to reduce CAD mortality and risk factors, there are no systematic reviews to validate these disparities. We conducted a search on PubMed, including Medline and PubMed Central, and Google Scholar. For this analysis, we selected articles published between 2000 and 2020 and those that fit the inclusion and exclusion criteria. Based on the type of study, we performed appropriate quality assessments and deleted studies with a score of less than seven or with a high risk of biases. The search strategy resulted in 322 studies. After inclusion and exclusion criteria were applied, we included 20 articles in the analysis of this review. This systematic review demonstrates that non-white races and women were less likely to receive the correct, clinically indicated, therapy for hyperlipidemia. A multi-faceted approach is required to solve this inequality in healthcare.

In the field of Automatic Music Transcription, note tracking systems constitute a key process in the overall success of the task as they compute the expected note-level abstraction out of a frame-based pitch activation representation. Despite its relevance, note tracking is most commonly performed using a set of hand-crafted rules adjusted in a manual fashion for the data at issue. In this regard, the present work introduces an approach based on machine learning, and more precisely supervised classification, that aims at automatically inferring such policies for the case of piano music. The idea is to segment each pitch band of a frame-based pitch activation into single instances which are subsequently classified as active or non-active note events. Results using a comprehensive set of supervised classification strategies on the MAPS piano data-set report its competitiveness against other commonly considered strategies for note tracking as well as an improvement of more than +10% in terms of F-measure when compared to the baseline considered for both frame-level and note-level evaluations. This research work is partially supported by Universidad de Alicante through the FPU program [UAFPU2014–5883] and the Spanish Ministerio de Economía y Competitividad through project TIMuL [No. TIN2013–48152–C2–1–R, supported by EU FEDER funds]. EB is supported by a UK RAEng Research Fellowship [grant number RF/128].

Imbalanced data is a typical problem in the supervised classification field, which occurs when the different classes are not equally represented. This fact typically results in the classifier biasing its performance towards the class representing the majority of the elements. Many methods have been proposed to alleviate this scenario, yet all of them assume that data is represented as feature vectors. In this paper we propose a strategy to balance a dataset whose samples are encoded as strings. Our approach is based on adapting the well-known Synthetic Minority Over-sampling Technique (SMOTE) algorithm to the string space. More precisely, data generation is achieved with an iterative approach to create artificial strings within the segment between two given samples of the training set. Results with several datasets and imbalance ratios show that the proposed strategy properly deals with the problem in all cases considered. This work was partially supported by the Spanish Ministerio de Economía y Competitividad through Project TIMuL (No. TIN2013- 48152-C2-1-R supported by EU FEDER funds), the Universidad de Alicante through the FPU program (UAFPU2014–5883) and grant GRE-16-04 .

Purpose/Objective(s) SBRT-SG 05 is a collaborative (SBRT-SG, GICOR and SEOR) prospective multicenter phase II trial testing SBRT and androgen deprivation therapy (ADT) in oligorecurrent prostate cancer patients. Materials/Methods Prostate cancer patients (hormone-sensitive or castration-resistant) in an oligorecurrent stage defined as less than 5 bone or lymph node metastases by Choline PET-CT or/and WB-DWI-MRI, after primary treatment, were assigned to receive ADT and SBRT (Vertebral metastases: 1 × 16-18Gy or 3 × 8-9Gy; lymph node metastases: 3 × 10-11 Gy or 6 × 7,5Gy; non-spinal bone metastases: 1 × 16Gy or 3 × 10Gy). Inclusion criteria included: more than 1 year from primary treatment to biochemical recurrence and PSA doubling time greater than 2 months. A minimum of 24 months of LhRh analogues from the time of the enrollment was required and concomitant treatment with chemotherapy, abiraterone or enzalutamide was not allowed. Oncologic outcomes defined by PCWG3 were evaluated separately for hormone-sensitive and castration-resistant patients, using Kaplan-Meier competing risks, and Cox regression. Toxicity was prospectively evaluated according to CTCAE.v4 criteria. Results From 07/2014 to 12/2019, 81 patients from 14 Spanish centers were recruited with a total of 117 oligometastases treated, 67 in lymph nodes, 43 in non-‐spinal bones and 7 in spinal bones. 14 patients were recruited in a castration-resistance status. Median follow-up was 41 months, (range 18 - 72 months). 13 hormone-sensitive (19,4%) and 8 castration-resistant (57,1%) oligorecurrent patients presented distant disease progression. Median distant progression-free survival (DPFS) was 54,2 months (IC95% = 48,2 – 60,3). 18 of the patients who progressed (85,7%) were treated with SBRT for the new lesions, 7 of them presented a subsequent distant progression (38,9%), with a median of second DPFS of 24,4 months (95% CI = 23,7 – 25,2). In the castration resistant subgroup, median DPFS was 33,5 months (range 14,8 – 52,1), 42,9% of them were free from distant disease progression at last follow-up, without the need to start second generation hormonal treatment. Tolerance and toxicity profiles were excellent, none of the patients developed toxicity ≥G3 or symptoms related to local progression of the disease. Conclusion Combination of SBRT and ADT is a safe treatment approach with favorable clinical outcomes for hormone-sensitive and castration-resistant prostate cancer patients. Validation studies are needed in castration-resistant patients. ClinicalTrials.gov Identifier: NCT02192788

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.

The involuntary force fluctuations associated with physiological (as distinct from pathological) tremor are an unavoidable component of human motor control. While the origins of physiological tremor are known to depend on muscle afferentation, it is possible that the mechanical properties of muscle-tendon systems also affect its generation, amplification and maintenance. In this paper, we investigated the dependence of physiological tremor on muscle length in healthy individuals. We measured physiological tremor during tonic, isometric plantarflexion torque at 30% of maximum at three ankle angles. The amplitude of physiological tremor increased as calf muscles shortened in contrast to the stretch reflex whose amplitude decreases as muscle shortens. We used a published closed-loop simulation model of afferented muscle to explore the mechanisms responsible for this behaviour. We demonstrate that changing muscle lengths does not suffice to explain our experimental findings. Rather, the model consistently required the modulation of γ-static fusimotor drive to produce increases in physiological tremor with muscle shortening—while successfully replicating the concomitant reduction in stretch reflex amplitude. This need to control γ-static fusimotor drive explicitly as a function of muscle length has important implications. First, it permits the amplitudes of physiological tremor and stretch reflex to be decoupled. Second, it postulates neuromechanical interactions that require length-dependent γ drive modulation to be independent from α drive to the parent muscle. Lastly, it suggests that physiological tremor can be used as a simple, non-invasive measure of the afferent mechanisms underlying healthy motor function, and their disruption in neurological conditions. This article is protected by copyright. All rights reserved

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.

Pattern Recognition tasks in the structural domain generally exhibit high accuracy results, but their time efficiency is quite low. Furthermore, this low performance is more pronounced when dealing with instance-based classifiers, since, for each query, the entire corpus must be evaluated to find the closest prototype. In this work we address this efficiency issue for the Nearest Neighbor classifier when data are encoded as two-dimensional code sequences, and more precisely strings and sequences of vectors. For this, a set of bounds is proposed in the distance metric that avoid the calculation of unnecessary distances. Results obtained prove the effectiveness of the proposal as it reduces the classification time in percentages between 80% and 90% for string representations and between 60% and 80% for data codified as sequences of vectors with respect to their corresponding non-optimized version of the classifier. This research work was partially funded by “Programa I+D+i de la Generalitat Valenciana, Spain” through grant APOSTD/2020/256 by the Spanish Ministerio de Economía, Industria y Competitividad through Project HISPAMUS (No. TIN2017-86576-R supported by EU FEDER funds).

Summary Objectives Show the results in pain and functionality, using low-dose radiotherapy in osteoarticular degenerative disorders (OADD). Review of the evidence. Material and methods Patients suffering from OADD with no response to other treatments, receive 6Gy in 6 fractions of 1 Gy, each other day, repeating the scheme if necessary. Evaluation of pain based on Visual Analogic Scale, analgesia intake and VonPannewitz score. Results Results observed in our series of patients treated with low doses of radiotherapy are similar to those previously published and reinforce the consideration of radiotherapy as an useful option for degenerative musculoskeletal disorders. Conclusion Low dose radiotherapy seems to be a good alternative for aged patients suffering from OADD.

Parkinson's disease (PD) is typically diagnosed and evaluated on the basis of overt motor dysfunction, however, subtle changes in the frequency spectrum of neural drive to muscles have been reported as well. During dynamic actions, coactive muscles of healthy adults often share a common source of 6-15 Hz (alpha-band) neural drive, creating synchronous alpha-band activity in their EMG signals. Individuals with PD commonly exhibit kinetic action tremor at similar frequencies, but the potential relationship between the intermuscular alpha-band neural drive seen in healthy adults and the action tremor associated with PD is not well-understood. A close relationship is most tenable during voluntary dynamic tasks where alpha-band neural drive is strongest in healthy adults, and where neural circuits affected by PD are most engaged. In this study, we characterized the frequency spectrum of EMG synchronization (intermuscular coherence) in 16 participants with PD and 15 age-matched controls during two dynamic motor tasks: (1) rotation of a dial between the thumb and index finger, and (2) dynamic scaling of isometric precision pinch force. These tasks produce different profiles of coherence between the first dorsal interosseous and abductor pollicis brevis muscles. We sought to determine if alpha-band intermuscular coherence would be amplified in participants with PD relative to controls, if such differences would be task-specific, and if they would correlate with symptom severity. We found that relative to controls, the PD group displayed amplified, but similarly task-dependent, coherence in the alpha-band. The magnitude of coherence during the rotation task correlated with overall symptom severity as per the UPDRS rating scale. Finally, we explored the potential for our coherence measures, with no additional information, to discriminate individuals with PD from controls. The area under the Receiver Operating Characteristic curve (AUC) indicated a clear separation between groups (AUC = 0.96), even though participants with PD were on their typical medication and displayed only mild-moderate symptoms. We conclude that a task-dependent, intermuscular neural drive within the alpha-band is amplified in PD. Its quantification via intermuscular coherence analysis may provide a useful tool for detecting the presence of PD, or assessing its progression.

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.

The motivation behind this research topic was to cut across conventional boundaries that separate movement neuroscience, biomechanics, and robotics. The aim was to underscore that brain and body collaborate to produce behavior in biological organisms. While this is a simple idea, compartmentalization in education and science has often artificially separated brain from body. We also bring forward research paradigms to investigate physical behavior at the interface between humans and interacting robots. Understanding human-robot physical interaction requires the understanding of the complex interplay between brain, body, and the external environment. This could be achieved by employing a neuro-mechanical approach to the study of human and robot movement.Within the context of a neuromechanical approach, we aimed to collate a research corpus that included work on experimental and neurophysiological analysis, computational modeling, and applications in rehabilitation and bio-inspired robotics. The 22 contributions to this research topic provide a wide range of perspectives and methodologies. The high-caliber contributions to this research topic also highlight the existence of a significant community of researchers interested in an interdisciplinary view toward the study of brain-body and human-robot interactions.

The nearest neighbor rule is one of the most considered algorithms for supervised learning because of its simplicity and fair performance in most cases. However, this technique has a number of disadvantages, being the low computational efficiency the most prominent one. This paper presents a strategy to overcome this obstacle in multi-class classification tasks. This strategy proposes the use of Prototype Reduction algorithms that are capable of generating a new training set from the original one to try to gather the same information with fewer samples. Over this reduced set, it is estimated which classes are the closest ones to the input sample. These classes are referred to as promising classes. Eventually, classification is performed using the original training set using the nearest neighbor rule but restricted to the promising classes. Our experiments with several datasets and significance tests show that a similar classification accuracy can be obtained compared to using the original training set, with a significantly higher efficiency. This work has been supported by the Vicerrectorado de Investigación, Desarrollo e Innovación de la Universidad de Alicante through the FPU programme (UAFPU2014–5883), the Spanish Ministerio de Educación, Cultura y Deporte through a FPU Fellowship (Ref. AP2012–0939) and the Spanish Ministerio de Economía y Competitividad through Project TIMuL (No. TIN2013-48152-C2-1-R, supported by UE FEDER funds).

Prototype selection is one of the most popular approaches for addressing the low efficiency issue typically found in the well-known k-Nearest Neighbour classification rule. These techniques select a representative subset from an original collection of prototypes with the premise of maintaining the same classification accuracy. Most recently, rank methods have been proposed as an alternative to develop new selection strategies. Following a certain heuristic, these methods sort the elements of the initial collection according to their relevance and then select the best possible subset by means of a parameter representing the amount of data to maintain. Due to the relative novelty of these methods, their performance and competitiveness against other strategies is still unclear. This work performs an exhaustive experimental study of such methods for prototype selection. A representative collection of both classic and sophisticated algorithms are compared to the aforementioned techniques in a number of datasets, including different levels of induced noise. Results report the remarkable competitiveness of these rank methods as well as their excellent trade-off between prototype reduction and achieved accuracy. This work has been supported by the Vicerrectorado de Investigación, Desarrollo e Innovación de la Universidad de Alicante through the FPU programme (UAFPU2014-5883), the Spanish Ministerio de Educación, Cultura y Deporte through a FPU Fellowship (Ref. AP2012-0939) and the Spanish Ministerio de Economía y Competitividad through Project TIMuL (No. TIN2013-48152-C2-1-R, supported by UE FEDER funds) and Consejería de Educación de la Comunidad Valenciana through project PROMETEO/2012/017.

We present the case of a patient with a glomus tumor that was atypical because of its large size and histologic characteristics. It was located in the dorsal-distal zone of the fifth ray of the left foot and was associated with a neuroma under the fifth metatarsal head. Although the pain (of a neurologic type) was attributed to the neuroma, the unknown nature and evolution of the dorsal lesion (glomus tumor) made surgical treatment necessary. Surgery, together with compensating treatment of the functional alterations of the patient's feet (pronation of the subastragalar joint, supination of the forefoot, and fifth metatarsal overload syndrome), resolved the case.

We explore the conceptual design and implementation of muscle redundancy and kinematic redundancy for anthropomorphic robots from three perspectives: (i) The control of tendon-driven systems, (ii) How the number of muscles define functional capabilities, and (iii) How too few synergies can be detrimental to functional versatility. Historically, roboticists prefer either rotational actuators located at each joint (i.e., rotational degree-of-freedom, DOF), or few linear actuators (i.e., two dedicated muscles per joint) for tendon-driven robots. In contrast, biological limbs have evolved to include too many muscles (Valero-Cuevas in Fundamentals of neuromechanics. Springer, Berlin (2015) [1]), which are thought to unnecessarily complicate their anatomy and control. The question, then, is why has evolution converged on these apparently under-determined (or redundant) solutions? If we really have extra muscles, then which muscle would you give up? By taking a formal mathematical approach to the control of tendons—which is the actual problem that confronts the nervous system—we have proposed a resolution to this apparent paradox by proposing that vertebrates may have, in fact, barely enough muscles to meet the numerous physical constraints for ecological functions (as opposed to simple laboratory tasks) (Valero-Cuevas in Fundamentals of neuromechanics. Springer, Berlin (2015) [1]; Loeb in Overcomplete musculature or underspecified tasks? Mot Control 4(1):81–83 (2000) [2]). This approach can be called Feasibility Theory, which describes how the anatomy of the system, and the constraints defining the task define the set of feasible actions the system can produce. The role of the (neural or engineered) controller is then, to find ways to use the mechanical capabilities of the combined controller-plant system to the fullest (Valero-Cuevas in Fundamentals of neuromechanics. Springer, Berlin (2015) [1]. Similarly, the effective mechanical design of a robotic limb, at a minimum, requires controllability (i.e., enough control degrees of freedom, or muscles) to produce arbitrary forces and movements (i.e., changes of state; Ogata in Modern control engineering. Prentice hall, India (2002) [3]). Force and movement capabilities have distinct governing equations and are, in fact, in competition with one another (e.g., a see-saw demonstrates, as per the Law of Conservation of Energy, how producing higher forces is associated with lower velocities and vice versa). Therefore, we explored the potential evolutionary pressures that may have shaped vertebrate limbs by evaluating how the number of muscles affects the competing demands to produce endpoint forces and velocities. A related concept that cuts across biological and robotic systems is the idea that the kinematics and kinetics of a wide variety of actions exhibit a low-dimensional structure that can be approximated with a few principal components (sometimes called descriptive synergies; Brock and Valero-Cuevas in Transferring synergies from neuroscience to robotics comment on hand synergies: integration of robotics and neuroscience for understanding the control of biological and artificial hands by M. Santello et al. Phys Life Rev 17:27 (2016) [4]; Rieffel et al. in Automated discovery and optimization of large irregular tensegrity structures. Comput Struct 87(5):368–379 (2009) [5]). This has been taken to mean that a few degrees of freedom suffice to produce versatile behavior in the real world. However, the fine behavioral details that distinguish different actions are, by definition, not captured by the commonalities among them. Thus, versatility in the real world likely depends on recognizing and executing fine distinctions among actions; which implies that more degrees of freedom of control are critical for true functional versatility. These three independent arguments support the perspective that creating anthropomorphic systems requires apparently redundant structures, because only then can they truly execute a wide variety of real-world tasks. In addition, we also present an open-access MATLAB toolbox that allows users from different backgrounds to explore these concepts in detail. We believe this new perspective will improve the conceptualization, understanding, and design of anthropomorphic systems.

We present Feasibility Theory, a conceptual and computational framework to unify today's theories of neuromuscular control. We begin by describing how the musculoskeletal anatomy of the limb, the need to control individual tendons, and the physics of a motor task uniquely specify the family of all valid muscle activations that accomplish it (its ‘feasible activation space'). For our example of producing static force with a finger driven by seven muscles, computational geometry characterizes—in a complete way—the structure of feasible activation spaces as 3-dimensional polytopes embedded in 7-D. The feasible activation space for a given task is the landscape where all neuromuscular learning, control, and performance must occur. This approach unifies current theories of neuromuscular control because the structure of feasible activation spaces can be separately approximated as either low-dimensional basis functions (synergies), high-dimensional joint probability distributions (Bayesian priors), or fitness landscapes (to optimize cost functions)., Frontiers in Computational Neuroscience, 12, ISSN:1662-5188