Total metabolic tumor volume on 18F-FDG PET/CT is a game-changer for patients with metastatic lung cancer treated with immunotherapy.

PURPOSE: Because of atypical response imaging patterns in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs), new biomarkers are needed for a better monitoring of treatment efficacy. The aim of this prospective study was to evaluate the prognostic value of volume-derived positron-emission tomography (PET) parameters on baseline and follow-up 18F-fluoro-deoxy-glucose PET (18F-FDG-PET) scans and compare it with the conventional PET Response Criteria in Solid Tumors (PERCIST). METHODS: Patients with metastatic NSCLC were included in two different single-center prospective trials. 18F-FDG-PET studies were performed before the start of immunotherapy (PETbaseline), after 6-8 weeks (PETinterim1) and after 12-16 weeks (PETinterim2) of treatment, using PERCIST criteria for tumor response assessment. Different metabolic parameters were evaluated: absolute values of maximum standardized uptake value (SUVmax) of the most intense lesion, total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), but also their percentage changes between PET studies (ΔSUVmax, ΔTMTV and ΔTLG). The median follow-up of patients was 31 (7.3-31.8) months. Prognostic values and optimal thresholds of PET parameters were estimated by ROC (Receiver Operating Characteristic) curve analysis of 12-month overall survival (12M-OS) and 6-month progression-free survival (6M-PFS). Tumor progression needed to be confirmed by a multidisciplinary tumor board, considering atypical response patterns on imaging. RESULTS: 110 patients were prospectively included. On PETbaseline, TMTV was predictive of 12M-OS [AUC (Area Under Curve) =0.64; 95% CI: 0.61 to 0.66] whereas SUVmax and TLG were not. On PETinterim1 and PETinterim2, all metabolic parameters were predictive for 12M-OS and 6M-PFS, the residual TMTV on PETinterim1 (TMTV1) being the strongest prognostic biomarker (AUC=0.83 and 0.82; 95% CI: 0.74 to 0.91, for 12M-OS and 6M-PFS, respectively). Using the optimal threshold by ROC curve to classify patients into three TMTV1 subgroups (0 cm3; 0-57 cm3; >57 cm3), TMTV1 prognostic stratification was independent of PERCIST criteria on both PFS and OS, and significantly outperformed them. Subgroup analysis demonstrated that TMTV1 remained a strong prognostic biomarker of 12M-OS for non-responding patients (p=0.0003) according to PERCIST criteria. In the specific group of patients with PERCIST progression on PETinterim1, low residual tumor volume (<57 cm3) was still associated with a very favorable patients' outcome (6M-PFS=73%; 24M-OS=55%). CONCLUSION: The absolute value of residual metabolic tumor volume, assessed 6-8 weeks after the start of ICPI, is an optimal and independent prognostic measure, exceeding and complementing conventional PERCIST criteria. Oncologists should consider it in patients with first tumor progression according to PERCIST criteria, as it helps identify patients who benefit from continued treatment. TRIAL REGISTRATION NUMBER: 2018-A02116-49; NCT03584334.

Validation of RUBY for Breast Cancer Knowledge Extraction From a Large French Electronic Medical Record System.

PURPOSE: RUBY is a tool for extracting clinical data on breast cancer from French medical records on the basis of named entity recognition models combined with keyword extraction and postprocessing rules. Although initial results showed a high precision of the system in extracting clinical information from surgery, pathology, and biopsy reports (≥92.7%) and good precision in extracting data from consultation reports (81.8%), its validation is needed before its use in routine practice. METHODS: In this work, we analyzed RUBY's performance compared with the manual entry and we evaluated the generalizability of the approach on different sets of reports collected on a span of 40 years. RESULTS: RUBY performed similarly or better than the manual entry for 15 of 27 variables. It showed similar performances when structuring newer reports but failed to extract entities for which changes in terminology appeared. Finally, our tool could automatically structure 15,990 reports in 77 minutes. CONCLUSION: RUBY can automate the data entry process of a set of variables and reduce its burden, but a continuous evaluation of the format and structure of the reports and a subsequent update of the system is necessary to ensure its robustness.

Land use and soil characteristics affect soil organisms differently from above-ground assemblages.

BACKGROUND: Land-use is a major driver of changes in biodiversity worldwide, but studies have overwhelmingly focused on above-ground taxa: the effects on soil biodiversity are less well known, despite the importance of soil organisms in ecosystem functioning. We modelled data from a global biodiversity database to compare how the abundance of soil-dwelling and above-ground organisms responded to land use and soil properties. RESULTS: We found that land use affects overall abundance differently in soil and above-ground assemblages. The abundance of soil organisms was markedly lower in cropland and plantation habitats than in primary vegetation and pasture. Soil properties influenced the abundance of soil biota in ways that differed among land uses, suggesting they shape both abundance and its response to land use. CONCLUSIONS: Our results caution against assuming models or indicators derived from above-ground data can apply to soil assemblages and highlight the potential value of incorporating soil properties into biodiversity models.

Validation and Improvement of a Convolutional Neural Network to Predict the Involved Pathology in a Head and Neck Surgery Cohort.

The selection of patients for the constitution of a cohort is a major issue for clinical research (prospective studies and retrospective studies in real life). Our objective was to validate in real life conditions the use of a Deep Learning process based on a neural network, for the classification of patients according to the pathology involved in a head and neck surgery department. 24,434 Electronic Health Records (EHR) from the first visit between 2000 and 2020 were extracted. More than 6000 EHR were manually classified in ten groups of interest according to the reason for consultation with a clinical relevance. A convolutional neural network (TensorFlow, previously reported by Hsu et al.) was then used to predict the group of patients based on their pathology, using two levels of classification based on clinically relevant criteria. On the first and second level of classification, macro-average performances were: 0.95, 0.83, 0.85, 0.97, 0.84 and 0.93, 0.76, 0.83, 0.96, 0.79 for accuracy, recall, precision, specificity and F1-score versus accuracy, recall and precision of 0.580, 580 and 0.582 for Hsu et al., respectively. We validated this model to predict the pathology involved and to constitute clinically relevant cohorts in a tertiary hospital. This model did not require a preprocessing stage, was used in French and showed equivalent or better performances than other already published techniques.

RUBY: Natural Language Processing of French Electronic Medical Records for Breast Cancer Research.

PURPOSE: Electronic medical records are a valuable source of information about patients' clinical status but are often free-text documents that require laborious manual review to be exploited. Techniques from computer science have been investigated, but the literature has marginally focused on non-English language texts. We developed RUBY, a tool designed in collaboration with IBM-France to automatically structure clinical information from French medical records of patients with breast cancer. MATERIALS AND METHODS: RUBY, which exploits state-of-the-art Named Entity Recognition models combined with keyword extraction and postprocessing rules, was applied on clinical texts. We investigated the precision of RUBY in extracting the target information. RESULTS: RUBY has an average precision of 92.8% for the Surgery report, 92.7% for the Pathology report, 98.1% for the Biopsy report, and 81.8% for the Consultation report. CONCLUSION: These results show that the automatic approach has the potential to effectively extract clinical knowledge from an extensive set of electronic medical records, reducing the manual effort required and saving a significant amount of time. A deeper semantic analysis and further understanding of the context in the text, as well as training on a larger and more recent set of reports, including those containing highly variable entities and the use of ontologies, could further improve the results.

Robotic Assisted Upper Limb Training Post Stroke: A Randomized Control Trial Using Combinatory Approach Toward Reducing Workforce Demands.

Post stroke upper limb rehabilitation is a challenging problem with poor outcomes as 40% of survivors have functionally useless upper limbs. Robot-aided therapy (RAT) is a potential method to alleviate the effort of intensive, task-specific, repetitive upper limb exercises for both patients and therapists. The present study aims to investigate how a time matched combinatory training scheme that incorporates conventional and RAT, using H-Man, compares with conventional training toward reducing workforce demands. In a randomized control trial (NCT02188628, www.clinicaltrials.gov), 44 subacute to chronic stroke survivors with first-ever clinical stroke and predominant arm motor function deficits were recruited and randomized into two groups of 22 subjects: Robotic Therapy (RT) and Conventional Therapy (CT). Both groups received 18 sessions of 90 min; three sessions per week over 6 weeks. In each session, participants of the CT group received 90 min of 1:1 therapist-supervised conventional therapy while participants of the RT group underwent combinatory training which consisted of 60 min of minimally-supervised H-Man therapy followed by 30 min of conventional therapy. The clinical outcomes [Fugl-Meyer (FMA), Action Research Arm Test and, Grip Strength] and the quantitative measures (smoothness, time efficiency, and task error, derived from two robotic assessment tasks) were independently evaluated prior to therapy intervention (week 0), at mid-training (week 3), at the end of training (week 6), and post therapy (week 12 and 24). Significant differences within group were observed at the end of training for all clinical scales compared with baseline [mean and standard deviation of FMA score changes between baseline and week 6; RT: Δ4.41 (3.46) and CT: Δ3.0 (4.0); p < 0.01]. FMA gains were retained 18 weeks post-training [week 24; RT: Δ5.38 (4.67) and week 24 CT: Δ4.50 (5.35); p < 0.01]. The RT group clinical scores improved similarly when compared to CT group with no significant inter-group at all time points although the conventional therapy time was reduced to one third in RT group. There were no training-related adverse side effects. In conclusion, time matched combinatory training incorporating H-Man RAT produced similar outcomes compared to conventional therapy alone. Hence, this study supports a combinatory approach to improve motor function in post-stroke arm paresis. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02188628.

A preliminary study on the relationship between proprioceptive deficits and motor functions in chronic stroke patients.

Although motor and sensory impairments of the upper limb after stroke have been widely studied, the relationship between sensory deficits and motor functions has been less thoroughly explored. In this ongoing study, we investigated the relationship between proprioceptive impairments and motor functions with 20 chronic stroke survivors. Their proprioceptive abilities were assessed with a passive joint position matching test using H-Man and their motor functions were assessed with ARAT (Action Research Arm Test) and FMA (Fugl Meyer Upper Extremity Assessment) clinical scores. The assessments were conducted before, during and after the therapy. Results indicated a significant difference between the proprioceptive outcomes of healthy and stroke participants (at baseline) in both matching accuracy (absolute error, p=0.02) and precision (variability of the signed error, p=0.03). Significant correlations were found between the proprioceptive assessment outcomes (assessed before the beginning of the motor rehabilitation) of stroke participants with impaired proprioception and their ARAT clinical scores assessed at the first follow-up (week 12) (rho =- 0.74 and p=0.047 for the absolute error; rho =-0.78 and p= 0.03 for the variability of the signed error). The results from this preliminary study indicated a significant relationship between proprioceptive impairments and motor function performances in proprioceptively impaired chronic stroke participants.

Widespread winners and narrow-ranged losers: Land use homogenizes biodiversity in local assemblages worldwide.

Human use of the land (for agriculture and settlements) has a substantial negative effect on biodiversity globally. However, not all species are adversely affected by land use, and indeed, some benefit from the creation of novel habitat. Geographically rare species may be more negatively affected by land use than widespread species, but data limitations have so far prevented global multi-clade assessments of land-use effects on narrow-ranged and widespread species. We analyse a large, global database to show consistent differences in assemblage composition. Compared with natural habitat, assemblages in disturbed habitats have more widespread species on average, especially in urban areas and the tropics. All else being equal, this result means that human land use is homogenizing assemblage composition across space. Disturbed habitats show both reduced abundances of narrow-ranged species and increased abundances of widespread species. Our results are very important for biodiversity conservation because narrow-ranged species are typically at higher risk of extinction than widespread species. Furthermore, the shift to more widespread species may also affect ecosystem functioning by reducing both the contribution of rare species and the diversity of species' responses to environmental changes among local assemblages.

Proprioceptive assessment in clinical settings: Evaluation of joint position sense in upper limb post-stroke using a robotic manipulator.

Proprioception is a critical component for motor functions and directly affects motor learning after neurological injuries. Conventional methods for its assessment are generally ordinal in nature and hence lack sensitivity. Robotic devices designed to promote sensorimotor learning can potentially provide quantitative precise, accurate, and reliable assessments of sensory impairments. In this paper, we investigate the clinical applicability and validity of using a planar 2 degrees of freedom robot to quantitatively assess proprioceptive deficits in post-stroke participants. Nine stroke survivors and nine healthy subjects participated in the study. Participants' hand was passively moved to the target position guided by the H-Man robot (Criterion movement) and were asked to indicate during a second passive movement towards the same target (Matching movement) when they felt that they matched the target position. The assessment was carried out on a planar surface for movements in the forward and oblique directions in the contralateral and ipsilateral sides of the tested arm. The matching performance was evaluated in terms of error magnitude (absolute and signed) and its variability. Stroke patients showed higher variability in the estimation of the target position compared to the healthy participants. Further, an effect of target was found, with lower absolute errors in the contralateral side. Pairwise comparison between individual stroke participant and control participants showed significant proprioceptive deficits in two patients. The proposed assessment of passive joint position sense was inherently simple and all participants, regardless of motor impairment level, could complete it in less than 10 minutes. Therefore, the method can potentially be carried out to detect changes in proprioceptive deficits in clinical settings.

The Influence of External Forces on Wrist Proprioception.

Proprioception combines information from cutaneous, joint, tendon, and muscle receptors for maintaining a reliable internal body image. However, it is still a matter of debate, in both neurophysiology and psychology, to what extent such body image is modified or distorted by a changing haptic environment. In particular, what is worth investigating is the contribution of external forces on our perception of body and joint configuration. The proprioceptive acuity of fifteen young participants was tested with a Joint Position Matching (JPM) task, performed with the dominant wrist under five different external forces, in order to understand to what extent they affect proprioceptive acuity. Results show that accuracy and precision in target matching do not change in a significant manner as a function of the loading condition, suggesting that the multi-sensory integration process is indeed capable of discriminating different sub-modalities of proprioception, namely the joint position sense and the sense of force. Furthermore, results indicate a preference for target undershooting when movements are performed in a viscous or high resistive force field, rather than passive or null fields in which subjects did not show any predominance for under/over estimation of their position.

Codification mechanisms of wrist position sense.

Proprioceptive signals from cutaneous, joint, tendon and muscle receptors create the basis for bodily perception and are known to be essential for motor control. However, which are the mechanisms underlying the proprioceptive signals and which are the variables that affect them is still a matter of debate. In particular, what is worth to investigate is, namely, the codification of proprioceptive information related to pointing movements of the wrist towards kinesthetic targets. In this work we asked 10 healthy adults to perform with their wrist a robot-aided proprioceptive matching task, in which the starting position of the matching movements was shifted forward or backward, in order to ascertain to which extent such shifts cause target over/under estimation and how important is movement's length on task performance. Results indicate that accuracy and precision of performance are highly correlated with the starting position and targets tended to be undershot when the active matching movements were longer. Moreover, further analysis revealed a consistent decrement of movement speed for shorter movements and conversely, faster displacement in case of backward of starting position.

Robotic assessment of the contribution of motor commands to wrist position sense.

Assessing joint position sense for rehabilitation after neurological injury provides a prognostic factor in recovery and long-term functional outcomes. A common method for testing joint position sense involves the active replication of a joint configuration presented via a passive movement. However, recent evidence showed how this sense is mediated by the centrally generated signals of motor command, such that movements produced volitionally may be coded differently from passive movements and accuracy may be different when matching targets presented actively. To verify this hypothesis we asked ten participants to actively replicate a target wrist angle with the help of a visual feedback in two conditions, which differed in the mode of target presentation: active (aaJPM) or passive (paJPM). The accuracy of target matching, directional bias and variability were analyzed, as well as speed and smoothness of the matching movement and criterion movement in the aaJPM. Overall results indicate higher accuracy and lower variability in the paJPM, while directional bias showed the tendency to overshoot the target regardless of condition. The speed did not differ in the two conditions and movements were smoother in the aaJPM, suggesting a higher confidence by participants in their matching ability. In conclusion, this study suggests that motor commands negatively affect the accuracy of joint position sense when matching involves the integration of visual and proprioceptive information.

Quantitative assessment of motor functions post-stroke: Responsiveness of upper-extremity robotic measures and its task dependence.

Technology aided measures offer a sensitive, accurate and time-efflcient approach for the assessment of sensorimotor function after neurological impairment compared to standard clinical assessments. This preliminary study investigated the relationship between task definition and its effect on robotic measures using a planar, two degree of freedom, robotic-manipulator (H-Man). Four chronic stroke participants (49.5±11.95 years, 2 Female, FMA: 37.5±13.96) and eight healthy control participants (26.25± 4.70 years, 2 Female) participated in the study. Motor functions were evaluated using line tracing and circle tracing tasks with dominant and nondominant hand of healthy and affected vs. non affected hand of stroke participants. The results show significant dependence of quantitative measures on investigated tasks.

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project.

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.

The Role of Visual and Haptic Feedback During Dynamically Coupled Bimanual Manipulation.

The mechanisms that underlie the control of bimanual actions in which the two hands act separately to manipulate different objects (uncoupled independent control) has been well studied. In contrast, much less is known about how the central nervous system controls bimanual actions that require the two hands act cooperatively to manipulate a single object (dynamically coupled control). Furthermore, there is scant research into the manual lateralization and role assignment in the processing of visual and haptic feedback during dynamically coupled bimanual tasks. In this experiment, we examined the role of the dominant and non-dominant hands during a dynamically coupled bimanual task in which visual and haptic feedback regarding object penetration were manipulated. Twelve subjects performed a bimanual grasp and reach task towards different target locations in the workspace by using two identical wrist robotic devices. Results showed haptic feedback is necessary for task completion, and that hand specialization plays a fundamental role in spatial and temporal coordination between the two limbs.

Has land use pushed terrestrial biodiversity beyond the planetary boundary? A global assessment.

Land use and related pressures have reduced local terrestrial biodiversity, but it is unclear how the magnitude of change relates to the recently proposed planetary boundary ("safe limit"). We estimate that land use and related pressures have already reduced local biodiversity intactness--the average proportion of natural biodiversity remaining in local ecosystems--beyond its recently proposed planetary boundary across 58.1% of the world's land surface, where 71.4% of the human population live. Biodiversity intactness within most biomes (especially grassland biomes), most biodiversity hotspots, and even some wilderness areas is inferred to be beyond the boundary. Such widespread transgression of safe limits suggests that biodiversity loss, if unchecked, will undermine efforts toward long-term sustainable development.

Local biodiversity is higher inside than outside terrestrial protected areas worldwide.

Protected areas are widely considered essential for biodiversity conservation. However, few global studies have demonstrated that protection benefits a broad range of species. Here, using a new global biodiversity database with unprecedented geographic and taxonomic coverage, we compare four biodiversity measures at sites sampled in multiple land uses inside and outside protected areas. Globally, species richness is 10.6% higher and abundance 14.5% higher in samples taken inside protected areas compared with samples taken outside, but neither rarefaction-based richness nor endemicity differ significantly. Importantly, we show that the positive effects of protection are mostly attributable to differences in land use between protected and unprotected sites. Nonetheless, even within some human-dominated land uses, species richness and abundance are higher in protected sites. Our results reinforce the global importance of protected areas but suggest that protection does not consistently benefit species with small ranges or increase the variety of ecological niches.

Robot-assisted assessment of wrist proprioception: does wrist proprioceptive acuity follow Weber's law?

Proprioception is essential for planning and controlling limb posture and movement. In our recent work, we introduced a standardized robot-aided method for measuring proprioceptive discrimination thresholds at the wrist to obtain reliable and accurate measures of proprioceptive acuity. Weber's law defines discrimination thresholds as a constant ratio between the just noticeable difference and the reference or standard stimulus. Reporting Weber's fractions thus provides the possibility of comparing results with the reports of others collected worldwide. This work aims to determine that Weber's Law holds for proprioceptive discrimination thresholds and to provide Weber's fraction for wrist joint proprioception. To this end, eight healthy subjects experienced two passive wrist movements of different amplitude and verbally indicated which was larger. An adaptive psychophysical procedure established the amplitude of the largest stimulus according to participants' responses. This comparison stimulus was then compared to a standard stimulus amplitude of 10°, 20°, 30° or 40°. The discrimination thresholds for each standard stimulus were established at the 75% correct response level. The obtained thresholds followed Weber's Law indicating that larger amplitudes were associated with higher discrimination thresholds. Based on a linear regression function the overall Weber's fraction, defined as the slope of the line, was computed to be 0.09. This result expands the present limited knowledge on wrist proprioception showing that its proprioceptive acuity follows Weber's law.

A preliminary study for quantitative assessment of upper limb proprioception.

Proprioception, or sense of position and movement of the body, strongly correlates with motor recovery of the hemiplegic arm. The evaluation of the awareness of the location of joints in space involves measuring the accuracy of joint-angle replication. Robotic devices allow an accurate manipulation of joint movements necessary to assess proprioceptive status. This study evaluated the proprioceptive performance of healthy subjects by mean of the H-Man, a planar robot designed for upper-limb rehabilitation to gather preliminary normative data for neurorehabilitation applications. Twelve participants were equally divided into Aged and Young groups and were asked to indicate when their dominant hand position matched a predefined target in the contralateral, sagittal and ipsilateral direction. Results indicated a better performance for movements towards the contralateral target in terms of both absolute and signed error while there was not a significant effect of age group. Error variability was not affected by the target location and participants' age. The present study established preliminary proprioceptive metrics that could assist in providing information about the normal range of proprioceptive acuity of healthy subjects of different age.

Green Plants in the Red: A Baseline Global Assessment for the IUCN Sampled Red List Index for Plants.

Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question 'How threatened are plants?' is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world's plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed.