Towards standard specifications for back-support exoskeletons

Back-support exoskeletons have shown the potential to improve workplace ergonomics by reducing the risk of low-back injury. To support the rapidly expanding landscape and to correspondingly promote correct adoption, standard specifications for back-support exoskeletons are desirable. We propose a list of properties and discuss their relevance to industrial applications

Analysis of human MDM4 variants in papillary thyroid carcinomas reveals new potential markers of cancer properties

A wild-type (wt) p53 gene characterizes thyroid tumors, except for the rare anaplastic histotype. Because p53 inactivation is a prerequisite for tumor development, alterations of p53 regulators represent an alternative way to impair p53 function. Indeed, murine double minute 2 (MDM2), the main p53 negative regulator, is overexpressed in many tumor histotypes including those of the thyroid. A new p53 regulator, MDM4 (a.k.a. MDMX or HDMX) an analog of MDM2, represents a new oncogene although its impact on tumor properties remains largely unexplored. We estimated levels of MDM2, MDM4, and its variants, MDM4-S (originally HDMX-S) and MDM4-211 (originally HDMX211), in a group of 57 papillary thyroid carcinomas (PTC), characterized by wt tumor protein 53, in comparison to matched contra-lateral lobe normal tissue. Further, we evaluated the association between expression levels of these genes and the histopathological features of tumors. Quantitative real-time polymerase chain reaction revealed a highly significant downregulation of MDM4 mRNA in tumor tissue compared to control tissue (P < 0.0001), a finding confirmed by western blot on a subset of 20 tissue pairs. Moreover, the tumor-to-normal ratio of MDM4 levels for each individual was significantly lower in late tumor stages, suggesting a specific downregulation of MDM4 expression with tumor progression. In comparison, MDM2 messenger RNA (mRNA) and protein levels were frequently upregulated with no correlation with MDM4 levels. Lastly, we frequently detected overexpression of MDM4-S mRNA and presence of the aberrant form, MDM4-211 in this tumor group. These findings indicate that MDM4 alterations are a frequent event in PTC. It is worthy to note that the significant downregulation of full-length MDM4 in PTC reveals a novel status of this factor in human cancer that counsels careful evaluation of its role in human tumorigenesis and of its potential as therapeutic target

Interdependence in Action: People with Visual Impairments and their Guides Co-constituting Common Spaces

Prior work on AI-enabled assistive technology (AT) for people with visual impairments (VI) has treated navigation largely as an independent activity. Consequently, much effort has focused on providing individual users with wayfinding details about the environment, including information on distances, proximity, obstacles, and landmarks. However, independence is also achieved by people with VI through interacting with others, such as in collaboration with sighted guides. Drawing on the concept of interdependence, this research presents a systematic analysis of sighted guiding partnerships. Using interaction analysis as our primary mode of data analysis, we conducted an empirical, qualitative study with 4 couples, each made up of person with a vision impairment and their sighted guide. Our results show how pairs used interactional resources such as turn-taking and body movements to both co-constitute a common space for navigation, and repair moments of rupture to this space. This work is used to present an exemplary case of interdependence and draws out implications for designing AI-enabled AT that shifts the emphasis away from independent navigation, and towards the carefully coordinated actions between people navigating togethe

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990–2015)

Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990–2001 to 81.9% in 2009–2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70–79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003–2015 versus 1990–2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level

Driver Stress State Evaluation by Means of Thermal Imaging: A Supervised Machine Learning Approach Based on ECG Signal

Traffic accidents determine a large number of injuries, sometimes fatal, every year. Among other factors affecting a driver&rsquo;s performance, an important role is played by stress which can decrease decision-making capabilities and situational awareness. In this perspective, it would be beneficial to develop a non-invasive driver stress monitoring system able to recognize the driver&rsquo;s altered state. In this study, a contactless procedure for drivers&rsquo; stress state assessment by means of thermal infrared imaging was investigated. Thermal imaging was acquired during an experiment on a driving simulator, and thermal features of stress were investigated with comparison to a gold-standard metric (i.e., the stress index, SI) extracted from contact electrocardiography (ECG). A data-driven multivariate machine learning approach based on a non-linear support vector regression (SVR) was employed to estimate the SI through thermal features extracted from facial regions of interest (i.e., nose tip, nostrils, glabella). The predicted SI showed a good correlation with the real SI (r = 0.61, p = ~0). A two-level classification of the stress state (STRESS, SI &ge; 150, versus NO STRESS, SI &lt; 150) was then performed based on the predicted SI. The ROC analysis showed a good classification performance with an AUC of 0.80, a sensitivity of 77%, and a specificity of 78%

Classification of Drivers&rsquo; Mental Workload Levels: Comparison of Machine Learning Methods Based on ECG and Infrared Thermal Signals

Mental workload (MW) represents the amount of brain resources required to perform concurrent tasks. The evaluation of MW is of paramount importance for Advanced Driver-Assistance Systems, given its correlation with traffic accidents risk. In the present research, two cognitive tests (Digit Span Test&mdash;DST and Ray Auditory Verbal Learning Test&mdash;RAVLT) were administered to participants while driving in a simulated environment. The tests were chosen to investigate the drivers&rsquo; response to predefined levels of cognitive load to categorize the classes of MW. Infrared (IR) thermal imaging concurrently with heart rate variability (HRV) were used to obtain features related to the psychophysiology of the subjects, in order to feed machine learning (ML) classifiers. Six categories of models have been compared basing on unimodal IR/unimodal HRV/multimodal IR + HRV features. The best classifier performances were reached by the multimodal IR + HRV features-based classifiers (DST: accuracy = 73.1%, sensitivity = 0.71, specificity = 0.69; RAVLT: accuracy = 75.0%, average sensitivity = 0.75, average specificity = 0.87). The unimodal IR features based classifiers revealed high performances as well (DST: accuracy = 73.1%, sensitivity = 0.73, specificity = 0.73; RAVLT: accuracy = 71.1%, average sensitivity = 0.71, average specificity = 0.85). These results demonstrated the possibility to assess drivers&rsquo; MW levels with high accuracy, also using a completely non-contact and non-invasive technique alone, representing a key advancement with respect to the state of the art in traffic accident prevention

Endothelial Dysfunction in COVID-19: A Unifying Mechanism and a Potential Therapeutic Target

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated a worldwide emergency, until the declaration of the pandemic in March 2020. SARS-CoV-2 could be responsible for coronavirus disease 2019 (COVID-19), which goes from a flu-like illness to a potentially fatal condition that needs intensive care. Furthermore, the persistence of functional disability and long-term cardiovascular sequelae in COVID-19 survivors suggests that convalescent patients may suffer from post-acute COVID-19 syndrome, requiring long-term care and personalized rehabilitation. However, the pathophysiology of acute and post-acute manifestations of COVID-19 is still under study, as a better comprehension of these mechanisms would ensure more effective personalized therapies. To date, mounting evidence suggests a crucial endothelial contribution to the clinical manifestations of COVID-19, as endothelial cells appear to be a direct or indirect preferential target of the virus. Thus, the dysregulation of many of the homeostatic pathways of the endothelium has emerged as a hallmark of severity in COVID-19. The aim of this review is to summarize the pathophysiology of endothelial dysfunction in COVID-19, with a focus on personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction as an attractive therapeutic option in this clinical setting

Phase i pharmacokinetic and pharmacodynamic study of lapatinib in combination with sorafenib in patients with advanced refractory solid tumors

Background. The epidermal growth factor receptor (EGFR) and ERBB2 (HER2) pathways and vascular endothelial growth factor (VEGF)-dependent angiogenesis have a pivotal role in cancer pathogenesis and progression. Robust experimental evidence has shown that these pathways are functionally linked and implicated in acquired resistance to targeted therapies making them attractive candidates for joined targeting. We undertook this phase I trial to assess the safety, the recommended dose for phase II trials (RPTD), pharmacokinetics (PK), pharmacodynamics (PD), and the preliminary antitumour activity of the combination of lapatinib and sorafenib in patients with advanced refractory solid tumours. Methods. Four cohorts of at least three patients each received lapatinib once daily and sorafenib twice daily together on a continuous schedule. Doses of lapatinib and sorafenib were escalated based on dose-limiting toxicities (DLTs) in the first treatment cycle following a traditional 3+3 design until the RPTD was reached. Additional patients were treated at the RPTD to characterise PK profiles of this combination and to investigate the potential interaction between lapatinib and sorafenib. Serum samples were collected at baseline and then prospectively every two cycles to assess changes in PD parameters. This trial is registered with ClinicalTrials.gov, number NCT00984425. Findings. Thirty patients with advanced refractory solid tumours were enroled. DLTs were grade three fatigue and grade 3 atypical skin rash observed at dose levels 3 and 4, respectively. The higher dose level explored (lapatinib 1250mg/day and sorafenib 400mg twice daily) represented the RPTD of the combination. The most common drug-related adverse events were fatigue (68%), hypocalcemia (61%), diarrhoea (57%), lymphopaenia (54%), anorexia (50%), rash (50%), and hypophosphatemia (46%). PK analysis revealed no significant effect of sorafenib on the PK profile of lapatinib. Of the 27 assessable patients for clinical activity, one achieved a confirmed complete response, four (15%) had a partial response, and 12 (44%) achieved disease stabilisation. The disease control rate overall was 63%. Interpretation. Combination treatment with lapatinib and sorafenib was feasible with promising clinical activity and without significant PK interactions. Long term tolerability seems to be challenging