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Recombinant allergens are currently the best option for serodiagnosis of human anisakiasis in terms of sensitivity and specificity. However, previous reports showed high rates of anisakiasis patients who were negative to Ani s 7 and especially to Ani s 1. Recently, Anisakis haemoglobin was described as a major allergen (Ani s 13). Although Ani s 13 belongs to a conserved protein family, it seems not to be a cross-reacting antigen because of the absence of IgE recognition against Ascaris haemoglobin in Anisakis patients. The aim of this study is to develop a more sensitive and specific diagnosis tool for Anisakis based on the recently discovered allergen Ani s 13. We obtained and purified recombinant Anisakis haemoglobin (rAni s 13) and the native form (nAni s 13). The recognition of both recombinant and native haemoglobins by anti-haemoglobin IgE from patients' sera was assessed by indirect ELISA and immunoblotting using 43 Anisakis sensitised patients and 44 non-Anisakis sensitised patients. Native Ani s 13 was also treated with periodate to study if oxidation of glycans destroys antibody binding. Furthermore, it was structurally characterised by negative staining electron microscopy and analytical ultracentrifugation. Recombinant Ani s 13 was only recognised by four patients with gastro-allergic anisakiasis (GAA) and immunoblotting analyses showed no bands. However, nAni s 13 was detected by 72.1% of Anisakis sensitised patients measured by indirect ELISA. Particularly, 18 (90%) out of 20 GAA patients were positive. Tetramers and octamers were the most abundant homomers of nAni s 13 but octamers had higher content of bound heme. None of the non-Anisakis sensitised patients were positive. Combined use of purified native form of Ani s 13 with current gold standards would improve the sensitivity and specificity for diagnosing anisakiasis., Instituto de Salud Carlos III, Universidad Complutense de Madrid, Depto. de Microbiología y Parasitología, Fac. de Farmacia, TRUE, pub

Sticholysins are pore-forming toxins produced by the sea anemone Stichodactyla helianthus. When they encounter a sphingomyelin-containing membrane, these proteins bind to it and oligomerize, a process that ends in pore formation. Mounting evidence indicates that StnII can favour the activity of StnI. Previous results have shown that these two isotoxins can oligomerize together. Furthermore, StnII appeared to potentiate the activity of StnI through the membrane-binding step of the process. Hence, isotoxin interaction should occur prior to membrane encounter. Here, we have used analytical ultracentrifugation to investigate the oligomerization of Stns in solution, both separately and together. Our results indicate that while StnI seems to be more prone to oligomerize in water solution than StnII, a small percentage of StnII in StnI–StnII mixtures promotes oligomerization., Para defenderse y atacar a sus presas, las anémonas marinas producen una serie de toxinas, entre las que se encuentran las actinoporinas (proteínas formadoras de poros). Es habitual que una anémona produzca varias isoformas de estas porinas, como es el caso de la anémona caribeña Stichodactyla helianthus, de la cual se han aislado hasta tres variantes, las conocidas como esticolisinas (Stn) I, II y III. Estas toxinas se unen a membranas en las que la esfingomielina, el lípido que reconocen específicamente, esté presente y disponible. Una vez unidas, es necesario que oligomericen para formar los poros que son, en definitiva, su forma activa final. En trabajos anteriores habíamos obtenido indicios que apuntaban a que tanto StnI como StnII eran capaces de formar oligómeros en ausencia de membranas. No solo eso, si no que StnII parecía capaz de favorecer la actividad de StnI si se las hacía actuar conjuntamente. Partiendo de la hipótesis de que estas dos ideas podían estar relacionadas, realizamos una serie de estudios de centrifugación analítica para evaluar cuantitativamente la oligomerización de StnI, StnII, y mezclas de StnI y StnII en diferentes proporciones. Los resultados obtenidos nos han permitido comprobar que StnI es más dada a formar homo-oligómeros que StnII. Además, revelan que pequeñas proporciones de StnII en una mezcla dominada por StnI resultan en una población de oligómeros mayor de lo que se anticiparía si StnI y StnII se asociaran independientemente. Un resultado que nos acerca a entender el mecanismo de acción de estas toxinas, y a vislumbrar la ventaja evolutiva que puede suponer a las anémonas la producción de varias isoformas de estas proteínas formadoras de poros., Ministerio de Ciencia e Innovación (MICINN), Universidad Complutense de Madrid/Banco de Santander, UnaEuropa, Juselius Foundation, CIB/CSIC, Internation Network of Computational and Structural Biology / Åbo Akademi, Sección Deptal. de Bioquímica y Biología Molecular (Biológicas), Fac. de Ciencias Biológicas, TRUE, pub

Chimeric antigen receptor-engineered (CAR)-T cell therapy remains limited by significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The optimal management of severe and/or refractory CRS/ICANS remains ill-defined. Anakinra has emerged as a promising agent based on preclinical data, but its safety and efficacy in CAR-T therapy recipients are unknown. The primary objective of this study was to evaluate the safety of anakinra to treat refractory CRS and ICANS after CAR-T therapy. The secondary objective was to evaluate the impact of key treatment-, patient-, and disease-related variables on the time to CRS/ICANS resolution and treatment-related mortality (TRM). We retrospectively analyzed the outcomes of 43 patients with B cell or plasma cell malignancies treated with anakinra for refractory CRS or ICANS at 9 institutions in the United States and Spain between 2019 and 2022. Cause-specific Cox regression was used to account for competing risks. Multivariable cause-specific Cox regression was used to estimate the effect of anakinra dose on outcomes while minimizing treatment allocation bias by including age, CAR-T product, prelymphodepletion (pre-LD) ferritin, and performance status. Indications for anakinra treatment were grade ≥2 ICANS with worsening or lack of symptom improvement despite treatment with high-dose corticosteroids (n = 40) and grade ≥2 CRS with worsening symptoms despite treatment with tocilizumab (n = 3). Anakinra treatment was feasible and safe; discontinuation of therapy because of anakinra-related side effects was reported in only 3 patients (7%). The overall response rate (ORR) to CAR-T therapy was 77%. The cumulative incidence of TRM in the whole cohort was 7% (95% confidence interval [CI], 2% to 17%) at 28 days and 23% (95% CI, 11% to 38%) at 60 days after CAR-T infusion. The cumulative incidence of TRM at day 28 after initiation of anakinra therapy was 0% in the high

[Background]: Chimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. We aimed to assess the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients with relapsed or refractory multiple myeloma., [Methods]: CARTBCMA-HCB-01 is a single-arm, multicentre study done in five academic centres in Spain. Eligible patients had relapsed or refractory multiple myeloma and were aged 18–75 years; with an Eastern Cooperative Oncology Group performance status of 0–2; two or more previous lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody; refractoriness to the last line of therapy; and measurable disease according to the International Myeloma Working Group criteria. Patients received an initial fractionated infusion of 3 × 106 CAR T cells per kg bodyweight in three aliquots (0·3, 0·9, and 1·8 × 106 CAR-positive cells per kg intravenously on days 0, 3, and 7) and a non-fractionated booster dose of up to 3 × 106 CAR T cells per kg bodyweight, at least 100 days after the first infusion. The primary endpoints were overall response rate 100 days after first infusion and the proportion of patients developing cytokine-release syndrome or neurotoxic events in the first 30 days after receiving treatment. Here, we present an interim analysis of the ongoing trial; enrolment has ended. This study is registered with ClinicalTrials.gov, NCT04309981, and EudraCT, 2019-001472-11., [Findings]: Between June 2, 2020, and Feb 24, 2021, 44 patients were assessed for eligibility, of whom 35 (80%) were enrolled. 30 (86%) of 35 patients received ARI0002h (median age 61 years [IQR 53–65], 12 [40%] were female, and 18 [60%] were male). At the planned interim analysis (cutoff date Oct 20, 2021), with a median follow-up of 12·1 months (IQR 9·1–13·5), overall response during the first 100 days from infusion was 100%, including 24 (80%) of 30 patients with a very good partial response or better (15 [50%] with complete response, nine [30%] with very good partial response, and six [20%] with partial response). Cytokine-release syndrome was observed in 24 (80%) of 30 patients (all grade 1–2). No cases of neurotoxic events were observed. Persistent grade 3–4 cytopenias were observed in 20 (67%) patients. Infections were reported in 20 (67%) patients. Three patients died: one because of progression, one because of a head injury, and one due to COVID-19., [Interpretation]: ARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach.

Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by the extracellular deposition of the transport protein transthyretin (TTR) as amyloid fibrils. Despite the progress achieved in recent years, understanding why different TTR residue substitutions lead to different clinical manifestations remains elusive. Here, we studied the molecular basis of disease-causing missense mutations affecting residues R34 and K35. R34G and K35T variants cause vitreous amyloidosis, whereas R34T and K35N mutations result in amyloid polyneuropathy and restrictive cardiomyopathy. All variants are more sensitive to pH-induced dissociation and amyloid formation than the wild-type (WT)-TTR counterpart, specifically in the variants deposited in the eyes amyloid formation occurs close to physiological pHs. Chemical denaturation experiments indicate that all the mutants are less stable than WT-TTR, with the vitreous amyloidosis variants, R34G and K35T, being highly destabilized. Sequence-induced stabilization of the dimer–dimer interface with T119M rendered tetramers containing R34G or K35T mutations resistant to pH-induced aggregation. Because R34 and K35 are among the residues more distant to the TTR interface, their impact in this region is therefore theorized to occur at long range. The crystal structures of double mutants, R34G/T119M and K35T/T119M, together with molecular dynamics simulations indicate that their strong destabilizing effect is initiated locally at the BC loop, increasing its flexibility in a mutation-dependent manner. Overall, the present findings help us to understand the sequence-dynamic-structural mechanistic details of TTR amyloid aggregation triggered by R34 and K35 variants and to link the degree of mutation-induced conformational flexibility to protein aggregation propensity.

The use of reduced-intensity conditioning (RIC) regimens has decreased the risk of nonrelapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). In contrast, disease relapse remains the most frequent cause of treatment failure and death. Owing to both their antimyeloma effect and immunomodulatory properties, novel drugs could improve outcomes after alloSCT. This phase II European Myeloma Network trial was designed to evaluate the combination of alloSCT with novel agents. The study was conducted to evaluate the toxicity and efficacy of RIC intensified with bortezomib (Bz) prior to alloSCT for high-risk (HR) multiple myeloma (MM) patients, as well as the efficacy of post-transplantation maintenance with Bz and lenalidomide (Len). Patients received RIC with Bz on days -9 and -2, fludarabine on days -6 to -4, and melphalan on day -3. Patients who were in complete response (CR) or near CR at day +100 post-transplantation received 6 cycles of Bz every 56 days, and the remaining received Bz, Len, and dexamethasone. Len maintenance was started on day +180 at a dose of 5 mg and continued until relapse or toxicity occurred. Of the 24 patients included, 21 were evaluable on day +100, including 12 in CR, 4 in very good partial response, 3 in partial response, and 2 with relapse or progression. The cumulative incidence (CuI) of relapse was 13.6% (95% confidence interval [CI], 3.2% to 31.3%) at 1 year and 28.5% (95% CI, 11.1% to 48.9%) at 2 years. The CuI of NRM was 21.1% (95% CI, 7.4% to 39.4%) at 2 years. With a median follow-up of 39 months (range, 1 to 67 months), the median event-free survival (EFS) was 29 months, and median overall survival (OS) was not reached. EFS and OS at 3 years were 42.5% (95% CI, 21.9% to 61.7%) and 74.01% (95% CI, 50.9% to 87.5%), respectively. The use of Bz within an RIC regimen allows for a high response rate after alloSCT. Maintenance with Bz and Len is feasible and provides remarkable results in terms of EFS and OS in HR MM pa

Release of aqueous contents from model lipid vesicles has been a standard procedure to evaluate pore formation efficiency by actinoporins, such as sticholysin II (StnII), for the last few decades. However, regardless of the probe of choice, the results reported that StnII action was never able to empty the vesicles completely. This was hard to explain if StnII pores were to be stable and always leaky for the probes used. To address this question, we have used a variety of probes, including rhodamine 6G or Tb3+, to test the permeability of StnII's pores. Our results indicate that calcein was in fact too large to fit through StnII's pores, and that the standard method in the field is actually reporting StnII-induced transient permeation of the membrane rather than the passage of solutes through the stable assembled pores. In order to evaluate the permeability of these structures, we used a dithionite-based assay, which showed that the final pores were in fact open. Thus, our results indicate that the stable actinoporins' pores are open in spite of plateaued classic release curves. Besides the proper pore, the first stages of pore formation would inflict serious damage to living cells as well., Universidad Complutense de Madrid (UCM)/Banco de Santander, ISB/ÅA Åbo Akademi University, Turku, Finland, Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, Magnus Ehrnrooth Foundation, Sección Deptal. de Bioquímica y Biología Molecular (Biológicas), Fac. de Ciencias Biológicas, TRUE, pub

The mode of interactions between palmitoyl lysophosphatidylcholine (palmitoyl lyso-PC) or other lysophospholipids (lyso-PLs) and palmitoyl ceramide (PCer) or other ceramide analogs in dioleoylphosphatidylcholine (DOPC) bilayers has been examined. PCer is known to segregate laterally into a ceramide-rich phase at concentrations that depend on the nature of the ceramides and the co-phospholipids. In DOPC bilayers, PCer forms a ceramide-rich phase at concentrations above 10 mol%. In the presence of 20 mol% palmitoyl lyso-PC in the DOPC bilayer, the lateral segregation of PCer was markedly facilitated (segregation at lower PCer concentrations). The thermostability of the PCer-rich phase in the presence of palmitoyl lyso-PC was also increased compared to that in the absence of palmitoyl lyso-PC. Other saturated lyso-PLs (e.g., palmitoyl lyso-phosphatidylethanolamine and lyso-sphingomyelin) also facilitated the lateral segregation of PCer in a similar manner as palmitoyl lyso-PC. When examined in the DOPC bilayer, it appeared that the association between palmitoyl lyso-PC and PCer was equimolar in nature. It is proposed that the interaction of PCer with lyso-PLs was driven by the need of ceramide to obtain a large-headgroup co-lipid, and saturated lyso-PLs were preferred co-lipids over DOPC because of the nature of their acyl chain. Structural analogs of PCer (1- or 3-deoxy-PCer) were also associated with palmitoyl lyso-PC, similarly to PCer, suggesting that the ceramide/lyso-PL interaction was not sensitive to structural alterations in the ceramide molecule. Binary complexes containing palmitoyl lyso-PC and ceramide were prepared, and these had a bilayer structure as ascertained by transmission electron microscopy. It is concluded that ceramides and lyso-PLs associated with each other both in binary bilayers and in ternary systems based on the DOPC bilayers. This association may have biological relevance under conditions in which both sphingomyelinases and phospholipase, Sigrid Juselius Foundation, Jane and Aatos Erkko Foundation, Magnus Ehrnrooth Foundation, Sección Deptal. de Bioquímica y Biología Molecular (Biológicas), Fac. de Ciencias Biológicas, TRUE, pub

[Resumen] La definición más actualizada de falla cardiaca avanzada incluye síntomas refractarios al tratamiento convencional, independiente de la fracción de eyección del ventrículo izquierdo, acompanados ˜ de elevación de péptidos natriuréticos. En esta nueva definición se destacan condiciones específicas como son la necesidad usual de diurético intravenoso, hospitalizaciones o consultas frecuentes por falla cardíaca, medicación inotrópica intermitente y arritmias malignas recurrentes. Esta condición está presente en aproximadamente 4 a 6% de los pacientes con falla cardiaca y se asocia a más síntomas, más comorbilidades y mayor mortalidad (hasta 75% a un ano). ˜ En este punto, las terapias convencionales han fallado o son refractarias y se requiere la toma de decisiones para instaurar tratamientos más avanzados (p. ej.: inotrópicos, asistencia ventricular, trasplante cardiaco, cuidado paliativo, entre otras). El tratamiento representa un reto para los sistemas de salud de Colombia por la necesidad de optimizar y racionalizar el uso de estos recursos; por esto se debe considerar que estos pacientes, en algún momento de su evolución, que sean remitidos para valoración en las Clínicas de Falla Cardíaca ya que estos servicios cuentan con personal altamente calificado y una estructura administrativa, logística y tecnológica que garantizan el acceso a un tratamiento integral y multidisciplinario con estándares de calidad internacionales que es lo que finalmente se requiere en estas condiciones. En el ‘‘Consenso colombiano de falla cardiaca avanzada’’ se presentan diferentes opciones de tratamiento a considerar y un modelo de atención integral que inicia desde el momento del diagnóstico hasta etapas refractarias y avanzadas., [Abstract] The most up-to-date definition of advanced heart failure includes symptoms refractory to conventional treatment (regardless of the left ventricular ejection fraction), accompanied by an elevation in natriuretic peptides. Specific conditions are highlighted in this new definition, such as the usual need of an intravenous diuretic, hospital admissions, or frequent consultations due to heart failure, intermittent inotropic medication, and recurrent malignant arrhythmias. This condition is present in approximately 4 to 6% of patients with heart failure and is associated with more symptoms, more comorbidities, and higher mortality (up to 75% at one year). On this point, the conventional treatments have failed, or are refractory, and decisions need to be taken to introduce more advanced treatments (for example: inotropic, ventricular assistance, palliative care, among others). The treatment represents a challenge for the Health Systems of Colombia due to the need to optimise and rationalise the use of these resources. For this reason, it must be considered that these patients, at any time during its course, may be sent for assessment in Heart Failure Clinics, as these services have highly qualified staff and an administrative, logistics, and technological structure that ensures access to an integral and multidisciplinary treatment with standards of international quality, which is what is finally required in these conditions. Different treatment options to consider are presented in the ‘‘Colombian consensus on advanced heart failure’’, as well as an integral care model that begins from the time of the diagnosis until the refractory and advanced stages.

Recombinant allergens are currently the best option for serodiagnosis of human anisakiasis in terms of sensitivity and specificity. However, previous reports showed high rates of anisakiasis patients who were negative to Ani s 7 and especially to Ani s 1. Recently, Anisakis haemoglobin was described as a major allergen (Ani s 13). Although Ani s 13 belongs to a conserved protein family, it seems not to be a cross reacting antigen because of the absence of IgE recognition against Ascaris haemoglobin in Anisakis patients. The aim of this study is to develop a more sensitive and specific diagnosis tool for Anisakis based on the recently discovered allergen Ani s 13. We obtained and purified recombinant Anisakis haemoglobin (rAni s 13) and the native form (nAni s 13). The recognition of both recombinant and native haemoglobins by anti-haemoglobin IgE from patients' sera was assessed by indirect ELISA and immunoblotting using 43 Anisakis sensitised patients and 44 non-Anisakis sensitised patients. Native Ani s 13 was also treated with periodate to study if oxidation of glycans destroys antibody binding. Furthermore, it was structurally characterised by negative staining electron microscopy and analytical ultracentrifugation. Recombinant Ani s 13 was only recognised by four patients with gastro-allergic anisakiasis (GAA) and immunoblotting analyses showed no bands. However, nAni s 13 was detected by 72.1% of Anisakis sensitised patients measured by indirect ELISA. Particularly, 18 (90%) out of 20 GAA patients were positive. Tetramers and octamers were the most abundant homomers of nAni s 13 but octamers had higher content of bound heme. None of the non-Anisakis sensitised patients were positive. Combined use of purified native form of Ani s 13 with current gold standards would improve the sensitivity and specificity for diagnosing anisakiasis.

The R2TP complex, comprising the Rvb1p-Rvb2p AAA-ATPases, Tah1p, and Pih1p in yeast, is a specialized Hsp90 co-chaperone required for the assembly and maturation of multi-subunit complexes. These include the small nucleolar ribonucleoproteins, RNA polymerase II, and complexes containing phosphatidylinositol-3-kinase-like kinases. The structure and stoichiometry of yeast R2TP and how it couples to Hsp90 are currently unknown. Here, we determine the 3D organization of yeast R2TP using sedimentation velocity analysis and cryo-electron microscopy. The 359-kDa complex comprises one Rvb1p/Rvb2p hetero-hexamer with domains II (DIIs) forming an open basket that accommodates a single copy of Tah1p-Pih1p. Tah1p-Pih1p binding to multiple DII domains regulates Rvb1p/Rvb2p ATPase activity. Using domain dissection and cross-linking mass spectrometry, we identified a unique region of Pih1p that is essential for interaction with Rvb1p/Rvb2p. These data provide a structural basis for understanding how R2TP couples an Hsp90 dimer to a diverse set of client proteins and complexes.

Sticholysin I and II (StnI and StnII) are pore-forming toxins that use sphingomyelin (SM) for membrane binding. We examined how hydrogen bonding among membrane SMs affected the StnI- and StnII-induced pore formation process, resulting in bilayer permeabilization. We compared toxin-induced permeabilization in bilayers containing either SM or dihydro-SM (lacking the trans 4 double bond of the long-chain base), since their hydrogen-bonding properties are known to differ greatly. We observed that whereas both StnI and StnII formed pores in unilamellar vesicles containing palmitoyl-SM or oleoyl-SM, the toxins failed to similarly form pores in vesicles prepared from dihydro-PSM or dihydro-OSM. In supported bilayers containing OSM, StnII bound efficiently, as determined by surface plasmon resonance. However, StnII binding to supported bilayers prepared from dihydro-OSM was very low under similar experimental conditions. The association of the positively charged StnII (at pH 7.0) with unilamellar vesicles prepared from OSM led to a concentration-dependent increase in vesicle charge, as determined from zeta-potential measurements. With dihydro-OSM vesicles, a similar response was not observed. Benzyl alcohol, which is a small hydrogen-bonding compound with affinity to lipid bilayer interfaces, strongly facilitated StnII-induced pore formation in dihydro-OSM bilayers, suggesting that hydrogen bonding in the interfacial region originally prevented StnII from membrane binding and pore formation. We conclude that interfacial hydrogen bonding was able to affect the membrane association of StnI- and StnII, and hence their pore forming capacity. Our results suggest that other types of protein interactions in bilayers may also be affected by hydrogen-bonding origination from SMs., Ministerio de Ciencia e Innovación (MICINN), Depto. de Bioquímica y Biología Molecular, Sección Deptal. de Bioquímica y Biología Molecular (Biológicas), Fac. de Ciencias Químicas, Fac. de Ciencias Biológicas, TRUE, pub

Aerial parts of Gonospermum fruticosum collected at several locations in the Canary Islands afforded, in addition to known compounds, four sesquiterpene alcohols related to costol and a sesquiterpene lactone, whose structures were established on the basis of their spectroscopic data and chemical transformations. Except for Gonospermum species collected on the island of Tenerife, those collected on the island of El Hierro and, in a previous study those from La Gomera, contain sesquiterpene lactones that can be used as chemotaxonomic markers confirming the inclusion of Gonospermum, Lugoa, and species of Tanacetum endemic to the Canary Islands in a genus that does not support the monophyly of Gonosperminae.

Antimicrobial peptides (AMPs) from amphibians and other eukaryotes recognize pathogenicity patterns mostly related to differences in membrane composition between the host and a variety of bacterial, fungal and protozoan pathogens. Compared to the other two groups, protozoa are fairly neglected targets in antimicrobial chemotherapy, despite their role as causative agents for scourges such as malaria, amoebiasis, Chagas' disease or leishmaniasis. Herein we review the scarce but growing body of knowledge addressing the use of amphibian AMPs on parasitic protozoa, the adaptations of the protozoan to AMP pressure and their impact on AMP efficacy and specificity, and the current and foreseeable strategies for developing AMPs into practical therapeutic alternatives against parasitic disease.

This paper presents a methodology for tuning PIDs considering the nominal performance and the robustness as control specifications. The synthesis procedure is similar to the Ziegler-Nichols method for PID controllers and can be easily used for industrial processes. As a workbench for testing the PID controller a mobile robot has been used. The path tracking problem of a mobile robot has been used as a workbench for testing the PID controller.

This paper presents a generic natural language interface that can be applied to the teleoperation of di!erent kinds of complex interactive systems. Through this interface the operators can ask for simple actions or more complex tasks to be executed by the system. Complex tasks will be decomposed into simpler actions generating a network of actions whose execution will result in the accomplishment of the required task. As a practical application, the system has been applied to the teleoperation of a real mobile robot, allowing the operator to move the robot in a partially structured environment through natural language sentences.

This paper describes the application of a natural language interface to the teleoperation of a mobile robot. Natural language communication with robots is a major goal, since it allows for non expert people to communicate with robots in his or her own language. This communication has to be flexible enough to allow the user to control the robot with a minimum knowledge about its details. In order to do this, the user must be able to perform simple operations as well as high level tasks which involve multiple elements of the system. For this ones, an adequate representation of the knowledge about the robot and its environment will allow the creation of a plan of simple actions whose execution will result in the accomplishment of the requested task

This paper presents a way of implementing a Model Based Predictive Controller (MBPC) for mobile robot path-tracking. The method uses a non-linear model of mobile robot dynamics and thus allows an accurate prediction of the future trajectories. Constraints on the maximum attainable angular velocity is also considered by the algorithm. A fuzzy approach is used to implement the MBPC. The fuzzy controller has been trained using a lookup-table scheme, where the database of fuzzy-rules has been obtained automatically from a set of input-output training patterns, computed with the predictive controller. Experimental results obtained when applying the fuzzy controller to a TRC labmate mobile platform are given in the paper.

This paper presents a way of implementing a Model Based Predictive Controller (MBPC) for mobile robot navigation when unexpected static obstacles are present in the robot environment. The method uses a non-linear model of mobile robot kinematics and thus allows an accurate prediction of the future trajectories. An ultrasonic ranging system has been used for obstacle detection. A Multilayer Perceptron is used to implement the MBPC, allowing real-time and also eliminating the need for data sensor high level processing. The perceptron has been trained to reproduce the MBPC behaviour in a supervised manner. Experimented results obtained when applying the neural network controller to a mobile robot are given in the paper.

This paper presents a local navigation method based on generalized predictive control. A modified cost function to avoid moving and static obstacles is presented. An Extended Kaiman Filter is proposed to predict the motions of the obstacles. A Neural Network implementation of this method is analysed. Simulation results are shown.

[ES] Objective To evaluate the effects of an intensive postoperative physiotherapy program focused on respiratory exercises in patients undergoing lobectomy by open thoracotomy. Design Quasi-experimental study. Setting Tertiary referral academic hospital. Participants 208 patients undergoing lobectomy by open thoracotomy. Interventions Control group patients (n = 102) received standard medical/nursing care, and experimental group patients (n = 106) added to the standard clinical pathway a daily physiotherapy program focused on respiratory exercises until discharge. Outcomes Analyzed outcomes were the frequency of postoperative pulmonary complications (PPCs) more amenable to physiotherapy (pneumonia, atelectasis and respiratory insufficiency) and length of hospital stay (LOS). Results Both groups were comparable regarding preoperative and surgical characteristics. Incidence of PPCs was 20.6% in control and 6.6% in experimental group (P = .003). Median (IQR) LOS in control group was 14 (7) days (Huber M estimator 14.21) and 12 (6) days (Huber M estimator 12.81) in experimental. Logistic regression model identified the evaluated physiotherapy program (P = .017; EXP [B] 95% CI 0.081-0.780) and % FEV1 (P = .042; EXP [B] 95% CI 0.941-0.999) as protective factors for the development of PPCs in patients undergoing lobectomy. Conclusions Implementing a postoperative intensive physiotherapy program focused on respiratory exercises reduces the risk of PPCs and resultant LOS on patients undergoing lobectomy.