Integrating immune checkpoint blockade with anti-neo/mutated antigens reactivity to increase the clinical outcome of immunotherapy

Antibodies to immune checkpoints have entered the clinical arena and have been shown to provide a clinical benefit for metastatic melanoma and, possibly, for other tumors as well. In this review paper we summarize this therapeutic activity and underline the functional mechanisms that may be involved. Among them, we discuss the so far neglected role of tumor-associated antigens (TAAs) deriving from tumor somatic mutations and summarize the results of recent trials showing the immunogenic strength of such TAAs which can be specifically targeted by T cells activated by immune checkpoint antibodies. Finally we discuss new immunotherapy approaches that involve the combination of self/shared- or neo-TAAs-based vaccines and immune checkpoint blockade antibodies, to increase the clinical response of metastatic melanoma patients

The future of the aeronautics: 360º reskilling and upskilling approach

The solution to challenges in aeronautics involves shifting traditional learning and development into reskilling and upskilling. However, some see it as a responsibility of industries, others as a responsibility of educational institutes, and some others as a responsibility of workers themselves. We review each stakeholder’s role, importance, and actions to take, applied to the aeronautics sector. The pathway to overcome the skills challenge is through an interconnected action, where all stakeholders work in synergy, and consider other pressing challenges, such as age/gender inclusion, with benefits for both single business growth and for prosperity of Aeronautics in post-covid times.info:eu-repo/semantics/publishedVersio

Fall risk assessment in elderly with and without history of falls: kinematic gait analysis: a comparative study

Objectives: The objective of this research was to verify if there was a variation in the MFC (Minimum Foot Clearance) value among elderly with and without history of falls and, if there were any, verify which joint of the lower limb was responsible for that variation. It was also a main objective to verify if there was a correlation between the risk of falling, achieved through the Timed Up and Go Test (TUG), and the MFC variation. Material and Methods: The sample consisted of a total of 30 elderly who met the inclusion and exclusion criteria. These were divided into the group without history of falls (n=15) and into the group with history of falls (n=15). The MFC and the joint movement amplitudes of the hip, knee and ankle, of the dominant lower limb, were assessed using the Kinovea programme and for the risk of fall assessment it was used the TUG. Results: There were no statistically significant differences in the MFC and TUG values between the groups with and without history of falls. However, there is a decrease of the MFC value for the group with history of falls, being the ankle the joint that most contributed to the MFC variation in the group without history of falls, and the knee in the group with history of falls. About the relation between MFC and TUG, it was obtained a negative correlation (r=-0,269) but it was not significant (p=0,150). Conclusion: In our sample no significant differences in the MFC value were obtained between the group with history of falls and the group without history of falls. Besides the lack of significant differences in the MFC value it was determined the articulation of the lower limb responsible for its variation, and it has been found, although with a p>0,05, that for the group with no history of falls it was the ankle that more contributed to this variation and the knee to the group with history of falls. Concerning to the TUG and MFC value correlation it wasn’t significant. Thus, it was concluded that the TUG use is more effective and sensitive in predicting the risk of falling when compared with the kinematic analysis to obtain the MFC value and the joints amplitude

Fall risk assessment in elderly with and without history of falls: strength analysis of lower limb: a comparative study

Objectives: The objective of this research was to analyse muscle performance criteria of the knee joints and ankle flexor and extensor muscles among elderly with and without history of falls. Material and methods: The sample was non-probabilistic, of convenience, comprising a total of 30 elderly (15 with history of falls and 15 without history of falls) who met the inclusion and exclusion criteria. Data were collected through a characterization questionnaire and through the Biodex System Isokinetic Dynamometer. The isokinetic assessment consisted in collecting the Peak Torque per unit of mass (N.m/BW) and ratio FlexorsCon/ExtensorsCon (%) of the knee joints and ankle flexor and extensor muscles, with 5 repetitions and the 60º/s angular speed. This collection has been made in both lower limbs. Results: The sample consisted of 30 individuals, 15 from the group without history of falls and 15 from the group with history of falls with average age of (69,17±4,77) years old. The muscle performance parameters were not significantly different between the groups (p>0,05). Conclusion: The group of elderly with history of falls showed lower Peak Torque numbers per unit of mass (N.m/BW) for the knee and ankle joint comparing with the group without history of falls. In present research also the values of the ratio flexorsCon/ExtensorsCon was analyzed weren't differences found in the knee and ankle joint. Although there are no statistically significant differences between results obtained, approach we believe it will be beneficial to include strengthening exercises for the flexors and extensors muscles of these joints, thereby contributing to the prevention of falls

Fall risk assessment in elderly with and without history of falls: relationship between disorders of balance, fear of falling and gait changes: a comparative study

Objectives: The aim of this study was to assess the changes that occur in the balance, fear of falling and kinematic parameters such as stride length, velocity and time support in elderly with and without a history of falling. Main objective was also to verify whether a relationship exists between changes in gait parameters evaluated, balance and fear of falling. Methods: The sample comprised 30 patients (15 with history of falls and 15 without a history of falls), which met the criteria for inclusion and exclusion. The kinematic evaluation was performed in the dominant leg, which was right in this sample. The stride length, speed and duration of support were assessed using the program Kinovea and for assessment of balance and fear of falling were assessed using the Berg Balance Scale and the Falls Efficacy Scale. Statistical analysis was performed with SPSS version 20. Results: There were no significant differences in the parameters analyzed, except for scores on the Berg Balance Scale (p=0.000) between groups with and without history of falls. However, there is a decrease in the length of the stride and duration of left leg support and the increased length of right leg support, the speed and the fear of falling. The relationship between the parameters obtained, there is only statistically significant result between speed and stride length (r=0.507, p=0.004) and between the score of the Berg Balance Scale and the stride length (r=0.393, p=0,032). Conclusion: Although not having obtained statistically significant results we can conclude that in elderly with a history of falls have changes in speed and stride length that can be related to balance disorders and the aging process itself. However, it is concluded that the use of the Berg Balance Scale is more responsive and effective in the detection of changes occurring in the individual after a fall, and subsequent evaluation of the risk of falling that performing a kinematic analysis

Fall risk assessment in elderly with and without history of falls: gait electromyographic analysis: a comparative study

Objectives: To determinate if there were differences in electromyography parameters of rectus anterior, biceps femoris, gluteus medius, soleus, gastrocnemius medialis and tibialis anterior muscles between group with and without history of falls during. Was analized the relationship between the levels of muscle activation and score in POMA (Performance-Oriented Mobility Assessment). Materials and Methods: This is a transversal, not experimental and comparative study. The sample was composed by 30 older adults, 15 with and 15 without history of falls. To collect the data of electromyography was used BIOPAC systems and followed the SENIAM guidelines. For the collection of kinematic data was used Kinovea program and for assess the risk of falling was applied POMA. Results: Individuals with history of falls present levels of muscle activity relatively to maximum voluntary contraction (MVC) higher in the dominant lower limb (right) compared to subjects without a history of falls, however these differences aren´t statistically significant (p>0,05). There is enormous variation between the sample in relation to phases of gait in which the muscles are more actives. The group with history of falls shows values lower than group without history of falls in POMA score, the difference is significant (p=0.001). The relationship between percentage of muscle activation and the values obtained in POMA not proved statistically significant (p>0,05). Conclusion: Although results obtained weren´t statistically significants, we can conclude that individuals with falls have higher levels of muscle activation relative to MVC that individuals without history of falls, it is believed that the changes are related to the development of strategies for increased stability during gait. There is considerable variability in phases in which the subjects engaged higher levels of muscle activation, which might occur due to task compensatory strategies or by the task have been made at speed of comfort for the individual. It follows that POMA is an instrument more sensitive and effective to identify the risk of falling in these individuals that the electromyographic analysis

Green Composites Based on Hedysarum coronarium with Outstanding FDM Printability and Mechanical Performance

The addition of natural scraps to biodegradable polymers has gained particular interest in recent years, allowing reducing environmental pollution related to traditional plastic. In this work, new composites were fabricated by adding 10% or 20% of Hedysarum coronarium (HC) flour to Poly (lactic acid) (PLA). The two formulations were first produced by twin screw extrusion and the obtained filaments were then employed for the fabrication of composites, either for compression molding (CM) or by fused deposition modeling (FDM), and characterized from a morphological and mechanical point of view. Through FDM it was possible to achieve dense structures with good wettability of the filler that, on the contrary, cannot be obtained by CM. The results indicate that the filler effectively acts as reinforcement, especially for FDM composites. The most remarkable enhancement was found in the flexural properties (+100% of modulus and ultimate strength), followed by tensile resistance and stiffness (+60%) and impact strength (+50%), whereas a moderate loss in tensile deformability was observed, especially at the highest loading. By adding HC to the polymeric matrix, it was possible to obtain a green, high-performance, and cost-effective composite, which could find applications for the fabrication of panels for furniture or the automotive industry

Knowledge Rich Natural Language Queries over Structured Biological Databases

Increasingly, keyword, natural language and NoSQL queries are being used for information retrieval from traditional as well as non-traditional databases such as web, document, image, GIS, legal, and health databases. While their popularity are undeniable for obvious reasons, their engineering is far from simple. In most part, semantics and intent preserving mapping of a well understood natural language query expressed over a structured database schema to a structured query language is still a difficult task, and research to tame the complexity is intense. In this paper, we propose a multi-level knowledge-based middleware to facilitate such mappings that separate the conceptual level from the physical level. We augment these multi-level abstractions with a concept reasoner and a query strategy engine to dynamically link arbitrary natural language querying to well defined structured queries. We demonstrate the feasibility of our approach by presenting a Datalog based prototype system, called BioSmart, that can compute responses to arbitrary natural language queries over arbitrary databases once a syntactic classification of the natural language query is made

Conceptual design of the enhanced coolant purification systems for the European HCLL and HCPB test blanket modules

The Coolant Purification Systems (CPSs) is one of the most relevant ancillary systems of European Helium Cooled Lead Lithium (HCLL) and Helium Cooled Pebble Bed (HCPB) Test Blanket Modules (TBMs) which are currently in the preliminary design phase in view of their installation and operation in ITER. The CPS implements mainly two functions: the extraction and concentration of the tritium permeated from the TBM modules into the primary cooling circuit and the chemistry control of helium primary coolant. During the HCLL and HCPB-TBSs (Test Blanket Systems) Conceptual Design Review (CDR) in 2015 it was recognized the need of reducing the tritium permeation into the Port Cell #16 of ITER. To achieve this and, then, to lower the tritium partial pressure in the Helium Cooling Systems in normal operation, the helium flow-rate treated by each CPS has been increased of almost one order of magnitude. In 2017, to satisfy the CDR outcomes and the new design requirements requested by Fusion for Energy (F4E, the European Domestic Agency for ITER), ENEA performed a preliminary design of the “enhanced” CPSs. This paper presents the current design of the “enhanced” CPSs, focusing on design requirements, assumptions, selection of technologies and preliminary components sizing