State and output feedback design for robust tracking of linear systems with rate limited actuators

A design technique (Control of Uncertain Systems with Bounded Inputs, Tarbouriech S, Garcia G, (Eds), Lecture Notes in Control and Information Sciences, vol. 227 , Springer: Berlin, 1997; 173–186) recently proposed for stabilization of a linear system with rate‐limited actuators is utilized to design feedback laws that cause the system output to track a desired command signal. This design technique combines two design techniques recently developed for linear systems with position limited actuators, piecewise‐linear LQ control (Automatica, 1994; 30 : 403–416) and low‐and‐high gain feedback (IEEE Trans. Automat. Control, 1996; 41 : 368–378), and hence takes advantage of both design techniques, while avoiding their disadvantages. In the case that only the output is available for feedback, the performance of the state feedback law is preserved by the use of a fast observer. An open‐loop exponentially unstable fighter aircraft is used to demonstrate the effectiveness of the proposed control design method. Copyright © 2002 John Wiley & Sons, Ltd.     

In vivo 23Na NMR studies of myotonic dystrophy

Myotonic dystrophy is an inherited multi-system disease. Its pathophysiology leading to muscle malfunction and damage is not well understood. ²³Na NMR spectroscopy was applied here for an in vivo comparative study of the calf muscles of 7 myotonic dystrophy patients at various stages of the disease and 11 healthy volunteers. Both the total sodium content, expressed as the ratio of the ²³Na and ¹H water signals, and the fast transverse relaxation time, T₂₁, determined from the triple quantum-filtered spectra, increased in correlation with the severity of the disease. The results demonstrate that ²³Na NMR enables the quantitation of myotonic dystrophy progression.     

Childhood Malignant Thymoma: Clinical, Therapeutic, and Immunohistochemical Considerations

Malignant thymomas are among the least common mediastinal tumors in the pediatric age group. Thymomas are considered malignant on the basis of macroscopic and microscopic invasiveness. As only 20 well-documented cases involving children have been reported in the literature, the pattern of responsiveness to therapy and the value of prognostic signs is obscure. Two cases of malignant pediatric thymomas are reported with pathognomonic histoimmunological features of aggressive thymoma. One was cured, with a follow-up of 70 months, and one died while on therapy. Analysis of the histological features and the immunoperoxidase staining displays the complexity of pediatric thymomas and the inability to prognosticate the outcome, respectively.     

Purification and characterization of placental heparanase and its expression by cultured cytotrophoblasts

The role of different extracellular matrix (ECM)-degrading enzymesin the normal functioning of the placenta is well documented.Heparan sulphate proteoglycan (HSPG) is an integral constituentof the placental and decidual ECM. Because this proteoglycanspecifically interacts with various macromolecules in the ECM,its degradation may disassemble the matrix. Hence, in the caseof the placenta, this may facilitate normal placentation andtrophoblast invasion. Crude placental specimens were collectedfrom first and third trimester placentas. Heparanase (endo-P-glucuronidase)was isolated and purified by ammonium sulphate precipitationfollowed by sequential chromatographies on carboxymethyl-, heparin-and ConA-Sepharose columns. The placental enzyme was furthercharacterized for its molecular weight and specific inhibitionby heparin, and was shown to resemble heparanase expressed byhighly metastatic tumour cells and activated cells of the immunesystem. In order to locate the source of heparanase activityin the placenta, primary cytotrophoblast cultures were established.Intact cells, as well as conditioned medium and cell lysates,were analysed for heparanase activity using metabolically sulphate-labelledECM as a natural substrate. Heparanase was highly active inlysates of cytotrophoblasts. This activity was also expressedby intact cytotrophoblasts seeded on ECM, but no activity couldbe detected in the culture medium. Incubation of the cytotrophoblastsin contact with ECM resulted in release of ECM-bound basic fibroblastgrowth factor (bFGF). We propose that the cytotrophoblasticheparanase facilitates placentation, through cytotrophoblastextravasation and localized neovascularization. cytotrophoblast/extracellular matrix/heparanase/heparan sulphate proteoglycan/placenta     

Antinuclear and related autoantibodies in sera of healthy subjects with IgA deficiency

The sera of 49 healthy IgA-deficient (SIgAD) subjects were evaluated for the presence of autoantibodies directed against 10 different nuclear and cytoskeletal antigens, as well as for the presence of the common lupus anti-DNA idiotype (16/6 Id). Twenty-nine sera were from IgG subclass-deficient subjects (4 = IgG2, 25 = IgG3), and 25 from normal healthy subjects, used as controls. The incidence of antinuclear but not anti-cytoskeletal antibodies were found to be significantly greater in the SIgAD group, as compared to the IgG-deficient subjects and the normal controls. Overall, 39% of SIgAD sera demonstrated polyreactivity, namely reactivity against more than one nuclear antigen. The incidence of specific antibody detection ranged from 37% against cardiolipin to 12% against RNP in the IgA-deficient group, albeit not with statistical significance in all cases when compared to the control group. Isotype evaluation of the antinuclear and related antibodies in the SIgAD group showed a greater tendency towards IgG. This increased incidence of autoantibody production in SIgAD may preceed the development of an overt autoimmune disease in the future.     

Treatment with lecinoxoids attenuates focal and segmental glomerulosclerosis development in nephrectomized rats

Focal segmental glomerulosclerosis (FSGS) is a scarring process associated with chronic low‐grade inflammation ascribed to toll‐like receptor (TLR) activation and monocyte migration. We developed synthetic, small‐molecule lecinoxoids, VB‐201 and VB‐703, that differentially inhibit TLR‐2‐ and TLR‐4‐mediated activation and monocyte migration. The efficacy of anti‐inflammatory lecinoxoid treatment on FSGS development was explored using a 5/6 nephrectomy rat model. Five‐sixths of nephrectomized rats were treated with lecinoxoids VB‐201, VB‐703 or PBS, for 7 weeks. Upon sacrifice, albumin/creatinine ratio, glomerulosclerosis, fibrosis‐related gene expression and the number of glomerular and interstitial monocyte were evaluated. Treatment of nephrectomized rats with lecinoxoids ameliorated glomerulosclerosis. The percentage of damaged glomeruli, glomerular sclerosis and glomeruli fibrotic score was significantly reduced following VB‐201 and VB‐703 treatment. VB‐703 attenuated the expression of fibrosis hallmark genes collagen, fibronectin (FN) and transforming growth factor β (TGF‐β) in kidneys and improved albumin/creatinine ratio with higher efficacy than did VB‐201, but only VB‐201 significantly reduced the number of glomerular and interstitial monocytes. These results indicate that treatment with TLR‐2, and more prominently, TLR‐4 antagonizing lecinoxioids, is sufficient to significantly inhibit FSGS. Moreover, inhibiting monocyte migration can also contribute to treatment of FSGS. Our data demonstrate that targeting TLR‐2‐TLR‐4 and/or monocyte migration directly affects the priming phase of fibrosis and may consequently perturb disease parthogenesis.     

Cardiovascular impact of testosterone therapy for hypogonadism

Introduction: Since 2010 some evidence supporting the possible increased cardiovascular (CV) risk related to testosterone treatment (TTh) has created much debate in the scientific community. Based on these results, the US Food and Drug Administration agency has questioned TTh for aging men recognizing its value only for classical hypogonadism due to genetic or organic causes. To better clarify this topic, we scrutinized and summarized, also by using meta-analytic methods, the data generated during the last 7 years, as derived from the analysis of randomized controlled trials (RCTs) on TTh and CV risk.

Areas covered: Analysis included 31 RCTs published between 2010 and 2018. Retrieved trials included 2675 and 2308 patients in TTh and placebo groups, respectively. The analysis documented that TTh was not associated with an increased CV mortality or morbidity either when overall or major adverse CV events were considered.

Expert commentary: Despite present evidence it is important to recognize that the duration of the available trials is short (lower that 3 years) limiting final conclusions on this topic. In particular, the available information on possible long-term effects of TTh on CV risk is limited. Long-term safety studies are advisable to better clarify these points.     

Frequency of hand movements as a possible diagnostic tool for parkinsonian bradykinesia. Proposal of a simple bedside test

Neurological Sciences - Bradykinesia, dysrhythmia, and decrement in hand movements (HM) are core symptoms of Parkinson’s disease (PD). The maximal rate of repetitive rhythm-preserving HM can...