Effects of metronome walking on long-term attractor divergence and correlation structure of gait: a validation study in older people.

This study investigates the effects of metronome walking on gait dynamics in older adults, focusing on long-range correlation structures and long-range attractor divergence (assessed by maximum Lyapunov exponents). Sixty older adults participated in indoor walking tests with and without metronome cues. Gait parameters were recorded using two triaxial accelerometers attached to the lumbar region and to the foot. We analyzed logarithmic divergence of lumbar acceleration using Rosenstein's algorithm and scaling exponents for stride intervals from foot accelerometers using detrended fluctuation analysis (DFA). Results indicated a concomitant reduction in long-term divergence exponents and scaling exponents during metronome walking, while short-term divergence remained largely unchanged. Furthermore, long-term divergence exponents and scaling exponents were significantly correlated. Reliability analysis revealed moderate intrasession consistency for long-term divergence exponents, but poor reliability for scaling exponents. Our results suggest that long-term divergence exponents could effectively replace scaling exponents for unsupervised gait quality assessment in older adults. This approach may improve the assessment of attentional involvement in gait control and enhance fall risk assessment.

Head-mounted eye tracker videos and raw data collected during breathing recognition attempts in simulated cardiac arrest.

This paper presents data collected by Pedrotti et al. (2022, 2024) [1,2], which includes videos captured using a Dikablis head-mounted eye tracker (Ergoneers GmbH, Germany), along with the corresponding raw data. The data collection aimed to assess participants' ability to recognize breathing in a simulated cardiac arrest scenario. Equipped with the eye tracker, participants entered a room where a manikin was positioned on the floor. Their task was to determine if the manikin was breathing and respond accordingly, such as initiating cardiopulmonary resuscitation if the victim was not breathing. Our analysis focused on examining looking time on the manikin's thorax by inspecting the videos. Potential applications of the dataset [3] include identifying fixation and saccades using custom algorithms, analyzing pupil diameter data, and conducting secondary analyses involving participant characteristics like age and gender as independent variables.

Restoring walking ability in older adults with arm-in-arm gait training: study protocol for the AAGaTT randomized controlled trial.

CONTEXT: Falls are a significant problem among older adults. While balance and functional exercises have been shown to be effective, it remains unclear whether regular walking has specific effects on reducing the risk of falls. RATIONALE: Older people who fall frequently have impaired gait patterns. Recent studies have suggested using interpersonal synchronization: while walking arm-in-arm, an older person synchronizes steps with a younger person to reinstate a better gait pattern. This method of gait training may reduce the risk of falls. OBJECTIVE: The aim is to assess the efficacy of an arm-in-arm gait-training program in older people. DESIGN: The arm-in-arm gait training trial (AAGaTT) is a single-site, open label, two-arm, randomized controlled trial. PARTICIPANTS: We will enroll 66 dyads of older people and their younger "gait instructors". The older participants must be > 70 years old with adequate walking ability. They must have experienced a fall in the year prior to study entry. INTERVENTION: Dyads will walk an indoor course for 30 min either side-by-side without contact (control group) or arm-in-arm while synchronizing their gait (intervention group). The gait training will be repeated three times a week for four weeks. OUTCOMES: The main outcome will be the walking speed measured in five-minute walking trials performed at baseline and at the end of each intervention week (week 1 - week 4), and at week 7. Gait quality will be assessed using accelerometers. We will also assess perceived physical activity and health using questionnaires. Finally, we will monitor fall incidence over 18 months. We will evaluate whether outcomes are more improved in the intervention group compared to the control group. In addition, interviews will be conducted to assess the perception of the gait training. EXPECTED RESULTS: Recent advances in the neurophysiology of motor control have shown that synchronizing gait to external cues or to a human partner can increase the efficiency of gait training. The expected benefits of arm-in-arm gait training are: reduced risk of falls, safe treatment with no adverse effects, and high adherence. This gait training program could be a low-cost intervention with positive effects on the health and well-being of seniors. TRIAL REGISTRATION: ClinicalTrials.gov NCT05627453. Date of registration: 11.25.2022.

Raw eye tracking data of healthy adults reading aloud words, pseudowords and numerals.

This paper describes data from de Chambrier et al. (2023). The dataset [2] contains raw eye tracking data of 36 healthy adults, collected using an EyeLink 1000 (SR Research Ltd., ON, Canada) during an on-screen reading task. Participants read 96 items including words, pseudowords and numerals. Each item was presented at the center of the screen until the participant produced an oral response and pressed the keyboard's space bar. Part of the data were analyzed to extract key metrics such as fixation number, fixation duration, saccade number, and saccade amplitude identified by the EyeLink 1000 [1]. Reuse potential includes (but is not limited to) pupil diameter data analysis, identification of fixations and saccades using custom algorithms, and secondary analyses using participant demographics (age, gender) as independent variables.

Reading numbers is harder than reading words: An eye-tracking study.

We recorded the eye movements of adults reading aloud short (four digit) and long (eight to 11 digit) Arabic numerals compared to matched-in-length words and pseudowords. We presented each item in isolation, at the center of the screen. Participants read each item aloud at their pace, and then pressed the spacebar to display the next item. Reading accuracy was 99 %. Results showed that adults make 2.5 times more fixations when reading short numerals compared to short words, and up to 7 times more fixations when reading long numerals with respect to long words. Similarly, adults make 3 times more saccades when reading short numerals compared to short words, and up to 9 times more saccades when reading long numerals with respect to long words. Fixation duration and saccade amplitude stay almost the same when reading short numerals with respect to short words. However, fixation duration increases by ∼50 ms when reading long numerals (∼300 ms) with respect to long words (∼250 ms), and saccade amplitude decreases up to 0.83 characters when reading long numerals with respect to long words. The pattern of findings for long numerals-more and shorter saccades as well as more and longer fixations-shows the extent to which reading long Arabic numerals is a cognitively costly task. Within the phonographic writing system, this pattern of eye movements stands for the use of the sublexical print-to-sound correspondence rules. The data highlight that reading large numerals is an unautomatized activity and that Arabic numerals must be converted into their oral form by a step-by-step process even by expert readers.

Distinct Cellular Origins and Differentiation Process Account for Distinct Oncogenic and Clinical Behaviors of Leiomyosarcomas.

In leiomyosarcoma (LMS), a very aggressive disease, a relatively transcriptionally uniform subgroup of well-differentiated tumors has been described and is associated with poor survival. The question raised how differentiation and tumor progression, two apparently antagonist processes, coexist and allow tumor malignancy. We first identified the most transcriptionally homogeneous LMS subgroup in three independent cohorts, which we named 'hLMS'. The integration of multi-omics data and functional analysis suggests that hLMS originate from vascular smooth muscle cells and show that hLMS transcriptional program reflects both modulations of smooth muscle contraction activity controlled by MYOCD/SRF regulatory network and activation of the cell cycle activity controlled by E2F/RB1 pathway. We propose that the phenotypic plasticity of vascular smooth muscle cells coupled with MYOCD/SRF pathway amplification, essential for hLMS survival, concomitant with PTEN absence and RB1 alteration, could explain how hLMS balance this uncommon interplay between differentiation and aggressiveness.

Effectiveness of rib fixation compared to pain medication alone on pain control in patients with uncomplicated rib fractures: study protocol of a pragmatic multicenter randomized controlled trial-the PAROS study (Pain After Rib OSteosynthesis).

BACKGROUND: Persistent pain and disability following rib fractures result in a large psycho-socio-economic impact for health-care system. Benefits of rib osteosynthesis are well documented in patients with flail chest that necessitates invasive ventilation. In patients with uncomplicated and simple rib fractures, indication for rib osteosynthesis is not clear. The aim of this trial is to compare pain at 2 months after rib osteosynthesis versus medical therapy. METHODS: This trial is a pragmatic multicenter, randomized, superiority, controlled, two-arm, not-blinded, trial that compares pain evolution between rib fixation and standard pain medication versus standard pain medication alone in patients with uncomplicated rib fractures. The study takes place in three hospitals of Thoracic Surgery of Western Switzerland. Primary outcome is pain measured by the brief pain inventory (BPI) questionnaire at 2 months post-surgery. The study includes follow-up assessments at 1, 2, 3, 6, and 12 months after discharge. To be able to detect at least 2 point-difference on the BPI between both groups (standard deviation 2) with 90% power and two-sided 5% type I error, 46 patients per group are required. Adjusting for 10% drop-outs leads to 51 patients per group. DISCUSSION: Uncomplicated rib fractures have a significant medico-economic impact. Surgical treatment with rib fixation could result in better clinical recovery of patients with uncomplicated rib fractures. These improved outcomes could include less acute and chronic pain, improved pulmonary function and quality of life, and shorter return to work. Finally, surgical treatment could then result in less financial costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04745520 . Registered on 8 February 2021.

Visual Fixation on the Thorax Predicts Bystander Breathing Detection in Simulated Out-of-Hospital Cardiac Arrest, but Video Debriefing With Eye Tracking Gaze Overlay Does Not Enhance Postallocation Success Rate: A Randomized Controlled Trial.

INTRODUCTION: Bystander cardiopulmonary resuscitation in out-of-hospital cardiac arrest is associated with higher survival rates. Even trained health care staff cannot assess breathing well enough to detect cardiac arrest. Recognition of cardiac arrest by lay rescuers might be overlooked in adult basic life support resuscitation guidelines, which explain what to do, but not how to do it. The 2015 Adult Advanced Life Support Resuscitation Guidelines recommend to "look for chest movement." We hypothesize (1) that instructing lay rescuers to look for chest movement allows detecting breathing (or lack thereof); (2) that showing a person their own recorded gaze overlay during a video debriefing intervention enhances breathing detection at postallocation; and (3) that the more time spent looking at a cardiac arrest victim's chest, the greater the probability of detecting breathing (or lack thereof). METHODS: Monocentric, blinded, prospective, 2-arm parallel randomized controlled trial with balanced randomization (1:1). The design entailed a preallocation simulation, an intervention (video debriefing with or without gaze overlay), and a postallocation simulation. A follow-up simulation took place after 6 months. The main outcome measured was success in detecting breathing. Participants were all prospective students of a bachelor's degree program in nursing. RESULTS: All participants performed better at postallocation (success rate at preallocation = 59%, postallocation = 79%, χ 2 = 7.22, P < 0.01) regardless of viewing their own gaze overlay during video debriefing. We failed to obtain a sufficient number of participants for the follow-up simulation. Instructing lay rescuers to look for chest movement allows them to detect breathing (or lack thereof). Each second spent looking at the thorax increased the odds of successfully detecting breathing by 38%. Mean thorax gaze duration significantly increased by 5.95 seconds (95% confidence interval = 4.71-7.31) from preallocation (3.46 seconds, SD = 4.16) to postallocation (9.41 seconds, SD = 5.98). Laypersons' median diagnosis time was 15.5 seconds (range = 2-63 seconds), similar to another study (13 seconds, range = 5-40 seconds). CONCLUSIONS: This is the second study in which the median time to decision exceeded the maximum 10 seconds recommended. International guidelines should consider increasing the time allowed for the "check breathing" step of bystander cardiopulmonary resuscitation procedures.

Starting Imatinib at 400 mg Daily in Patients with Gastrointestinal Stromal Tumors Harboring KIT Exon 9 Mutations: A Retrospective, Multicenter Study.

BACKGROUND: Retrospective analyses suggest that patients with advanced KIT exon 9-mutated gastrointestinal stromal tumors (GISTs) receiving imatinib 800 mg (rather than 400 mg) daily have better outcomes. In the adjuvant setting, the question of the optimal dose of imatinib remains unsettled. OBJECTIVE: We aimed to retrospectively assess the activity of imatinib 400 mg in both the adjuvant and the advanced settings. PATIENTS AND METHODS: We performed a multicenter study of patients with KIT exon 9-mutated GIST starting imatinib at 400 mg daily. We examined the relapse-free survival (RFS) among high-risk patients either receiving or not receiving adjuvant imatinib. In patients with advanced disease, progression-free survival (PFS, progression under imatinib 400 mg), time to imatinib failure (TIF, progression under imatinib 400, then 800 mg upon first progression), and overall survival (OS) were analyzed. RESULTS: In the post-operative setting (n = 37), 20 patients received adjuvant imatinib. Median RFS in high-risk patients receiving adjuvant imatinib (n = 14) was not reached (95% CI 17.5-46.6) versus 13.6 months (95% CI 4.7-13.6) for those who did not (p = 0.37), after a median follow-up of 58 months. RFS at 36 months was 63% (30.3-96.6) versus 40% (95% CI 0-82.9), p = 0.2. In advanced disease (n = 28), median PFS, TIF and OS were 12.7 months (95% CI 6.1-18.2), 21.0 months (95% CI 17.4-28.1) and 47.0 months (95% CI 33.5-69.2), respectively. CONCLUSIONS: Despite the limitations of a retrospective analysis and the small number of patients, the benefit of adjuvant imatinib 400 mg daily in high-risk patients appeared relevant. Patients with advanced disease receiving imatinib 400 mg with subsequent dose escalation had a TIF similar to that observed with an initial dose of 800 mg. Intra-patient dose escalation in this setting might be an option.

Predictive Factors of Recovery after an Acute Lateral Ankle Sprain: A Longitudinal Study.

A prominent feature of ankle sprains is their variable clinical course. The difficulty of providing a reliable early prognosis may be responsible for the substantial rate of poor outcomes after an ankle sprain. The aim of the present study was to evaluate the prognostic value of objective clinical measures, pain, and functional scores for ankle sprain recovery. Fifty-two participants suffering from lateral ankle sprain were included. Sprain status was assessed four weeks following injury and included evaluations of ankle range of motion, strength, function, and pain. Seven months following injury, a second assessment classified the patients into recovered and non-recovered groups using ankle ability measures. Following a predictor pre-selection procedure, logistic regressions evaluated the association between the four-week predictors and the seven-month recovery status. Twenty-seven participants (52%) fully recovered and 25 did not (48%). The results of the logistic regressions showed that walking pain was negatively associated with the probability of recovering at seven months (odds ratio: 0.71, 95% CI: 0.53-0.95). Pain four weeks after ankle sprain had relevant predictive value for long-term recovery. Special attention should be paid to patients reporting persistent pain while walking four weeks following sprain to reduce the risk of chronicity.

Nationwide incidence of sarcomas and connective tissue tumors of intermediate malignancy over four years using an expert pathology review network.

BACKGROUND: Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France. METHODS: The nationwide incidence of sarcoma or TIM (2013-2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed. RESULTS: Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1-0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p<10-6) are significantly higher with sarcomas subtypes with an incidence above 1/106 per. CONCLUSIONS: This nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (1<106/year) are less likely to be included in clinical trials.

Postoperative Outcome of Surgery with Pancreatic Resection for Retroperitoneal Soft Tissue Sarcoma: Results of a Retrospective Bicentric Analysis on 50 Consecutive Patients.

BACKGROUNDS: Multivisceral resection is the standard treatment for retroperitoneal sarcoma (RPS) during which pancreas resection may be necessary. METHODS: All consecutive patients operated for RPS with pancreatectomy in 2 expert centers between 1993 and 2018 were retrospectively analyzed. RESULTS: Fifty patients (median age: 57 years, IQR: [46-65]) with a primary (n = 33) or recurrent (n = 17) RPS underwent surgery requiring pancreas resection (distal pancreatectomy (DP) (n = 43), pancreaticoduodenectomy (PD) (n = 5), central pancreatectomy (n = 1), and atypical resection (n = 1)). Severe postoperative morbidity (Clavien-Dindo III-IV) was observed in 14 patients (28%), and 7 of them (14%) required reoperation for anastomotic bowel leakage (n = 5), gastric volvulus (n = 1), or hemorrhage (n = 1). Pancreas-related complications occurred in 25 patients (50%): 10 postoperative pancreatic fistulas (POPF) (grade A (n = 12), grade B (n = 6), grade C (n = 1)), 13 delayed gastric emptying (grade A (n = 8), grade B (n = 4), grade C (n = 1)), 1 hemorrhage (grade C). Postoperative mortality was 4% (n = 2), all following PD, caused by a massive intraoperative air embolism and by a multiple organ failure after anastomotic leakage. Pathological analysis confirmed pancreatic involvement in 17 (34%) specimens. Microscopically complete resection (R0) was achieved in 22 (44%) patients. After a follow-up of 60 months, 36 patients (75%) were still alive, among whom 27 without recurrence (56%). CONCLUSION: Pancreatic resection during RPS surgery is associated with significant postoperative morbidity and mortality. PD should be avoided whenever possible while other procedures seemed achievable without excessive morbidity and with long-term survival.

Extraskeletal Myxoid Chondrosarcoma: Clinical and Molecular Characteristics and Outcomes of Patients Treated at Two Institutions.

Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics. Methods: This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database. Results: 59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival. Conclusion: In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.

Lower Rate of CTNNB1 Mutations and Higher Rate of APC Mutations in Desmoid Fibromatosis of the Breast: A Series of 134 Tumors.

Desmoid fibromatosis (DF) is a rare, locally aggressive, nonmetastasizing fibroblastic/myofibroblastic tumor with a tendency to recur and an unpredictable clinical course. A "wait-and-see" policy is the new standard of care. DF are characterized by activating alterations of the wnt/ß-catenin pathway: CTNNB1 or adenomatous polyposis coli gene (APC) mutations (these mutations being mutually exclusive). Desmoid-type fibromatosis of the breast (DFB) is rare with an incidence of 0.2% of breast tumors. The diagnosis of DFB is difficult, as it must be distinguished from metaplastic carcinoma and other spindle cell lesions. Sequencing of 128 DFB identified a lower rate of CTNNB1 mutations using Sanger (65.6%) or Sanger+next-generation sequencing (77.7%) and a higher rate of APC mutations (11.8%) than in all-site DF. By excluding patients with familial adenomatous polyposis (n=2), the rate of APC mutations in DFB was high (10.7%). The distribution of CTNNB1 mutations in DFB was different from all-site DF, with a higher rate of T41A (68.9%), a lower rate of S45F (5.7%), and a similar rate of S45T (12.6%). By combining the 2 molecular techniques in a 2-step manner (Sanger, then next-generation sequencing), we increased the detection rate of CTNNB1 mutations and lowered the rate of wild-type tumors from 34.4% to 9.8%, therefore improving the diagnosis of DFB. The identification of the exon 3 CTNNB1 mutation in breast spindle cell lesions is a highly specific tool for the diagnosis of DFB, in addition to extensive immunohistochemical analysis. Our study also underlines the importance of APC in DFB tumorigenesis. These findings have significant implications for patient care and management.

The Role of Hip Abductor Strength in Identifying Older Persons at Risk of Falls: A Diagnostic Accuracy Study.

BACKGROUND/OBJECTIVES: Early detection of fall risk in persons older than 65 is of clinical relevance, but the diagnostic accuracy of currently used functional tests (eg short physical performance battery [SPPB] and timed up and go test [TUG]) to assess older persons' fall risks remains moderate. Recent literature highlights the importance of strong hip abductors to prevent falls. We thus aimed to assess the diagnostic accuracy of hip abductor strength measures to assess older persons' fall risks. METHODS: Hip abductor maximum voluntary isometric strength (ABD MVIS), rate of force generation (ABD RFG), and the SPPB and TUG functional fall risk assessments were assessed in 60 persons aged over 65 years (82.0 ± 6.1 years). The diagnostic accuracy (area under the curve [AUC], sensitivity [sens], specificity [spec], positive predictive value [PPV], negative predictive value [NPV], and positive and negative likelihood ratios [LR+, LR-]) was evaluated at a clinically important 90% sensitivity level. Cut-off values for clinical use were calculated. RESULTS: In our population, hip ABD MVIS (AUC 0.8, sens 90.6%, spec 57.1%, PPV 70.7%, NPV 84.2%, LR+ 2.1, LR- 0.2, and cut-off value ≤ 1.1 N/kg) and hip ABD RFG (AUC 0.8, sens 90.6%, spec 46.4%, PPV 65.9%, NPV 81.3%, LR+ 1.7, LR- 0.2, and cut-off ≤ 8.47 N/kg/s) show diagnostic accuracy comparable to other fall risk assessments (SPPB and TUG) and a high net sensitivity when used in a test battery. CONCLUSION: Hip ABD MVIS or RFG shows good diagnostic accuracy to differentiate between older fallers and nonfallers compared to the chosen external criterion history of falls. The high net sensitivity when hip ABD MVIS or RFG is combined with currently used fall risk assessments shows promise in contributing value to a test battery and should be investigated further in longitudinal studies.

A comprehensive review on the diagnosis and management of intimal sarcoma of the pulmonary artery.

Only a few hundred cases of intimal sarcomas of pulmonary artery (ISPA) were reported on the literature. Diagnosis of this rare entity is a challenging dilemma with the need for a high expertise in the radiological and pathological identification of ISPA. Treatment strategies rely initially on an early aggressive surgery aiming for complete surgical resection with clear margins while no clear recommendations guiding the choice for additional drug therapy or radiotherapy exist. In this article, we perform an extensive review of the literature on ISPA with details on the clinical presentation, diagnosis and management strategies. An additional goal of this paper is to make practicing oncologists aware of this rare entity with clear idea on the initial management.

Complexity of human walking: the attractor complexity index is sensitive to gait synchronization with visual and auditory cues.

BACKGROUND: During steady walking, gait parameters fluctuate from one stride to another with complex fractal patterns and long-range statistical persistence. When a metronome is used to pace the gait (sensorimotor synchronization), long-range persistence is replaced by stochastic oscillations (anti-persistence). Fractal patterns present in gait fluctuations are most often analyzed using detrended fluctuation analysis (DFA). This method requires the use of a discrete times series, such as intervals between consecutive heel strikes, as an input. Recently, a new nonlinear method, the attractor complexity index (ACI), has been shown to respond to complexity changes like DFA, while being computed from continuous signals without preliminary discretization. Its use would facilitate complexity analysis from a larger variety of gait measures, such as body accelerations. The aim of this study was to further compare DFA and ACI in a treadmill experiment that induced complexity changes through sensorimotor synchronization. METHODS: Thirty-six healthy adults walked 30 min on an instrumented treadmill under three conditions: no cueing, auditory cueing (metronome walking), and visual cueing (stepping stones). The center-of-pressure trajectory was discretized into time series of gait parameters, after which a complexity index (scaling exponent alpha) was computed via DFA. Continuous pressure position signals were used to compute the ACI. Correlations between ACI and DFA were then analyzed. The predictive ability of DFA and ACI to differentiate between cueing and no-cueing conditions was assessed using regularized logistic regressions and areas under the receiver operating characteristic curves (AUC). RESULTS: DFA and ACI were both significantly different among the cueing conditions. DFA and ACI were correlated (Pearson's r = 0.86). Logistic regressions showed that DFA and ACI could differentiate between cueing/no cueing conditions with a high degree of confidence (AUC = 1.00 and 0.97, respectively). CONCLUSION: Both DFA and ACI responded similarly to changes in cueing conditions and had comparable predictive power. This support the assumption that ACI could be used instead of DFA to assess the long-range complexity of continuous gait signals. However, future studies are needed to investigate the theoretical relationship between DFA and ACI.

Differences in the miRNA signatures of chronic musculoskeletal pain patients from neuropathic or nociceptive origins.

BACKGROUND: The quality of life for millions of people worldwide is affected by chronic pain. In addition to the effect of chronic pain on well-being, chronic pain has also been associated with poor health conditions and increased mortality. Due to its multifactorial origin, the classification of pain types remains challenging. MicroRNAs (miRNA) are small molecules that regulate gene expression. They are released into the bloodstream in a stable manner under normal and pathological conditions and have been described as potential biomarkers. In the present study, we aimed to investigate whether pain may induce an aberrant, specific dysregulation of miRNA expression, depending on the origin of the pain. METHODS AND FINDINGS: To do so, we measured the expression changes of 184 circulating miRNAs (c-miRNAs) in the plasma samples of patients with different origins of chronic musculoskeletal pain. After statistical analyses, we identified seven c-miRNA candidates that were differentially expressed depending on the nociceptive or neuropathic origin of the pain. We then developed a two c-miRNA signature (hsa-miR-320a and hsa-miR-98-5p) that was able to correctly classify the pain type of 70% of the patients from the validation set. CONCLUSIONS: In conclusion, circulating miRNAs are promising biomarkers to identify and characterize the chronic pain type and to further improve its clinical management.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

BACKGROUND: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS: Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING: Nanobiotix SA.

BiomiMETRIC Assistance Tool: A Quantitative Performance Tool for Biomimetic Design.

This article presents BiomiMETRIC, a quantitative performance tool for biomimetic design. This tool is developed as a complement to the standard ISO 18458 Biomimetics-terminology, concepts, and methodology to quantitatively evaluate the biomimetics performance of a design, a project, or a product. BiomiMETRIC is aimed to assist designers, architects, and engineers to facilitate the use of the biomimetic approach beyond the existing frameworks, and to provide an answer to the following question: How can a quantitative evaluation of biomimetic performance be carried out? The biomimetic quantitative performance tool provides a method of quantitative analysis by combining the biomimetic approach with the impact assessment methods used in life-cycle analysis. Biomimetic design is divided into eight steps. The seventh step deals with performance assessment, verifying that the concept developed is consistent with the 10 sustainable ecosystem principles proposed by the Biomimicry Institute. In the application of the biomimetic quantitative performance tool, stone wool and cork are compared as insulation materials used in biomimetic architecture projects to illustrate the relevance and added value of the tool. Although it is bio-based, cork has a lower biomimetic performance according to the indicators used by the biomimetic quantitative performance tool presented in this article.