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This paper considers the issue of linear-quadratic regulator (LQR) design for nonlinear systems with the use of smooth state and input transformations. The proposed design methodology is considered in the stabilisation task of the Pendubot, which is based on the concept of feedback equivalent control systems. It turns out that it is possible to find a controller that ensures comparable dynamics of the closed-loop system in the vicinity of the set point regardless of the state-space representation adopted. In addition, the synthesis of suboptimal controllers according to the LQR strategy ensuring equal dynamics at the equilibrium point is presented. The properties of the studied controllers were investigated in a simulation environment and using experimental tests. The detailed forms of transformations and linear approximations given can be regarded as ready-made procedures that can be applied to stabilise similar mechanical systems in robotics.

The aim of this paper is to test the usefulness of a new approach based on partial feedback linearization to control the Pendubot. The control problem stated in the article is to stabilize the Pendubot in the upright position. In particular, properties of the closed-loop system and the zero dynamics are investigated and illustrated by results of simulations. Next, the performance of a hybrid-like controller in the case of input saturation is evaluated by conduction extensive simulation trails. The experimental results suggest that the considered control methodology can be successfully applied for a real system.

TTN gene truncating variants are common in dilated cardiomyopathy (DCM), although data on their clinical significance is still limited. We sought to examine the frequency of truncating variants in TTN in patients with DCM, including familial DCM (FDCM), and to look for genotype-phenotype correlations. Clinical cardiovascular data, family histories and blood samples were collected from 72 DCM probands, mean age of 34 years, 45.8% FDCM. DNA samples were examined by next generation sequencing (NGS) with a focus on the TTN gene. Truncating mutations were followed up by segregation study among family members. We identified 16 TTN truncating variants (TTN trunc) in 17 probands (23.6% of all cases, 30.3% of FDCM, 17.9% of sporadic DCM). During mean 63 months from diagnosis, there was no difference in adverse cardiac events between probands with and without TTN truncating mutations. Among relatives 29 mutation carriers were identified, nine were definitely affected (31%), eight probably affected (27.6%) one possibly affected (3.4%) and eleven were not affected (37.9%). When relatives with all affected statuses were combined, disease penetrance was still incomplete (62.1%) even after exclusion of unaffected relatives under 40 (82%) and was higher in males versus females. In all mutation carriers, during follow-up, 17.4% had major adverse cardiac events, and prognosis was significantly worse in men than in women. In conclusion, TTN truncating variants were observed in nearly one fourth of young DCM patient population, in vast majority without conduction system disease. Incomplete penetrance suggests possible influence of other genetic and/or environmental factors on the course of cardiotitinopathy. Counseling should take into account sex and incomplete penetrance.

This paper considers the issue of linear-quadratic regulator (LQR) design for nonlinear systems with the use of smooth state and input transformations. The proposed design methodology is considered in the stabilisation task of the Pendubot, which is based on the concept of feedback equivalent control systems. It turns out that it is possible to find a controller that ensures comparable dynamics of the closed-loop system in the vicinity of the set point regardless of the state-space representation adopted. In addition, the synthesis of suboptimal controllers according to the LQR strategy ensuring equal dynamics at the equilibrium point is presented. The properties of the studied controllers were investigated in a simulation environment and using experimental tests. The detailed forms of transformations and linear approximations given can be regarded as ready-made procedures that can be applied to stabilise similar mechanical systems in robotics. [ABSTRACT FROM AUTHOR]

The aim of this paper is to test the usefulness of a new approach based on partial feedback linearization to control the Pendubot. The control problem stated in the article is to stabilize the Pendubot in the upright position. In particular, properties of the closed-loop system and the zero dynamics are investigated and illustrated by results of simulations. Next, the performance of a hybrid-like controller in the case of input saturation is evaluated by conduction extensive simulation trails. The experimental results suggest that the considered control methodology can be successfully applied for a real system. [ABSTRACT FROM AUTHOR]

Infections caused by tick-borne pathogens such as Bartonella spp., Borrelia burgdorferi s.l., Coxiella burnetii and Rickettsia spp. are capable of causing serious lesions of the mitral and aortic valves, leading to a need for valve replacement. Objectives. The aim of the study was to determine whether such cases are sporadic or frequent. An additional goal was to establish effective diagnostic methods to detect these infections. Material and methods. The study involved 148 patients undergoing valve replacement. Blood samples were drawn for serological testing. Samples of the removed mitral and aortic valves were tested with PCR and immunohistochemical staining. Results. Specific antibodies to Bartonella spp. were detected in 47 patients (31.7%) and in 1 of the healthy controls (1%) (p < 0.05). Antibodies to B. burgdorferi spirochetes were found in 18 of the patients (12.2%) and in 6 blood donors from the control group (5.8%) (p < 0.1). Antibodies to Rickettsia spp. were detected in 12 (8.1%) and to C. burnetii phase I and II antigens in the serum of 1 patient. All the participants in the control group were seronegative to C. burnetii and Rickettsia spp. antigens. PCR tests for detection of Bartonella spp., B. burgdorferi s.l., C. burnetii and Rickettsia spp. DNA in the valve samples were all negative. Inflammation foci with mononuclear lymphoid cells in the aortic and mitral valves were seen in sections stained with hematoxiline and eozine. In sections dyed using the indirect immunofluorescence method with hyperimmune sera, Bartonella spp. and Rickettsia spp. were found. Conclusions. The results obtained indicate that laboratory diagnostics for patients with heart disorders should be expanded to include tests detecting tick-borne zoonoses such as bartonelloses, Lyme borreliosis, rickettsioses and Q fever. [ABSTRACT FROM AUTHOR]

[Display omitted] Hydrocortisone is mainly used in the substitution treatment of adrenal insufficiency which results in a dysregulation of cortisol. Compounding of hydrocortisone capsules remains the only low-dose oral treatment suitable for the pediatric population. However, capsules often show non-compliance in mass and content uniformity. Three-dimensional printing offers the prospect of practising personalized medicine for vulnerable patients like children. The goal of this work is to develop low-dose solid oral forms containing hydrocortisone by hot-melt extrusion coupled with fused deposition modeling for the pediatric population. Formulation, design and processes temperatures were optimized to produce printed forms with the desired characteristics. Red mini-waffle shapes containing drug loads of 2, 5 and 8 mg were successfully printed. This new 3D design allow to release more than 80 % of the drug in 45 min indicating a conventional release like the one obtained with capsules. Mass and content uniformity, hardness and friability tests complied with European Pharmacopeia specifications, despite the considerable challenge of the small dimensions of the forms. This study demonstrates that FDM can be used to produce innovative pediatric-friendly printed shapes of an advanced pharmaceutical quality to practice personalize medicine. [ABSTRACT FROM AUTHOR]

TTN gene truncating variants are common in dilated cardiomyopathy (DCM), although data on their clinical significance is still limited. We sought to examine the frequency of truncating variants in TTN in patients with DCM, including familial DCM (FDCM), and to look for genotype-phenotype correlations. Clinical cardiovascular data, family histories and blood samples were collected from 72 DCM probands, mean age of 34 years, 45.8% FDCM. DNA samples were examined by next generation sequencing (NGS) with a focus on the TTN gene. Truncating mutations were followed up by segregation study among family members. We identified 16 TTN truncating variants (TTN trunc) in 17 probands (23.6% of all cases, 30.3% of FDCM, 17.9% of sporadic DCM). During mean 63 months from diagnosis, there was no difference in adverse cardiac events between probands with and without TTN truncating mutations. Among relatives 29 mutation carriers were identified, nine were definitely affected (31%), eight probably affected (27.6%) one possibly affected (3.4%) and eleven were not affected (37.9%). When relatives with all affected statuses were combined, disease penetrance was still incomplete (62.1%) even after exclusion of unaffected relatives under 40 (82%) and was higher in males versus females. In all mutation carriers, during follow-up, 17.4% had major adverse cardiac events, and prognosis was significantly worse in men than in women. In conclusion, TTN truncating variants were observed in nearly one fourth of young DCM patient population, in vast majority without conduction system disease. Incomplete penetrance suggests possible influence of other genetic and/or environmental factors on the course of cardiotitinopathy. Counseling should take into account sex and incomplete penetrance. [ABSTRACT FROM AUTHOR]

[Display omitted] Many active principles belong to the second class of the Biopharmaceutics Classification System due to their low aqueous solubility. Elaboration of new solid oral forms by hot-melt extrusion and fused deposition modeling appears as a promising tool to increase the dissolution rate of these drugs. Indeed, hot-melt extrusion allows the amorphisation of drugs and forms with complex geometries are built by 3D printing. Therefore, the goal of this work is to enhance the dissolution rate of poorly soluble drugs using hot-melt extrusion coupled with fused deposition modeling. Four formulations containing Affinisol® 15LV, Kollidon® VA64 and a challenging amount of itraconazole (25 % (wt.)) were successfully printed into forms of 20, 50 and 80 % infill densities. Differential scanning calorimetry analysis has shown that itraconazole remained amorphous during 52 weeks. The drug release rate was highly improved compared to itraconazole in a crystalline form. The dissolution rate was influenced by the infill density and the polymer composition of printed forms which could modify respectively the surface to volume ratio and the distribution of the components in the printed forms. One formulation printed with 20 % infill density even had a solubility profile similar to that of Sporanox®, the commercialized drug product in Belgium. [ABSTRACT FROM AUTHOR]

This paper presents a solution for universal multidrive control system, which can be used as a base for the rapid prototyping of various kinematic structures, particularly in robotics, for multiple-axis synchronization tasks, or as a test bed for verification of modern control algorithms for electric drives. The example of the practical application of the proposed system was also given: It was used during prototyping process of a quadruped walking robot, powered by multiple electric motors. The abilities and performance of the system were verified with the attempt to realize the dynamic gait of the robot. [ABSTRACT FROM PUBLISHER]

[Display omitted] The standard of care for patients with Adrenal Insufficiency (AI) is suboptimal. Administration of hydrocortisone three times a day produces plasma cortisol fluctuations associated with negative health outcomes. Furthermore, there is a high inter-individual variability in cortisol need, necessitating a personalized approach. It is hypothesized that a personalized, sustained release formulation would enhance the pharmacotherapy by mimicking the physiological cortisol plasma concentration at a higher level. Therefore, a novel 24 h sustained release 3D printed (3DP) hydrocortisone formulation has been developed (M3DICORT) by coupling hot-melt extrusion with fused deposition modeling. A uniform drug distribution in the 3DP tablets is demonstrated by a content of 101.66 ± 1.60 % with an acceptance value of 4.01. Furthermore, tablets had a stable 24 h dissolution profile where the intra-batch standard deviation was ± 2.8 % and the inter-batch standard deviation was ± 6.8 %. Tablet height and hydrocortisone content were correlated (R2 = 0.996), providing a tool for easy dose personalization. Tablets maintained critical quality attributes, such as dissolution profile (f2 > 60) and content uniformity after process transfer from a single-screw extruder to a twin-screw extruder. Impurities were observed in the final product which should be mitigated before clinical assessment. To our knowledge, M3DICORT is the first 3DP hydrocortisone formulation specifically developed for AI. [ABSTRACT FROM AUTHOR]