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.     

Percutaneous obliteration of the cystic duct with a holmium:yttrium-aluminum-garnet laser: results of in vitro and animal experiments.

OBJECTIVE. The purpose of this study was to investigate the feasibility of using a holmium:yttrium-aluminum-garnet laser to permanently occlude the cystic duct in order to isolate the gallbladder from the biliary-enteric circulation and prevent gallstone formation. MATERIALS AND METHODS. To determine the optimal laser parameters (power and pulsing rate) for cystic duct thermocoagulation, 20 freshly excised porcine gallbladders with intact cystic ducts underwent low-energy (0.075-0.085 J/pulse) or high-energy (0.20-0.25 J/pulse) thermocoagulation. Histopathologic examination was done to determine the extent of cystic duct injury. After in vitro experiments, percutaneous transcholecystic laser thermocoagulation of the cystic duct was performed on 23 anesthetized domestic pigs (four controls). Cholangiograms immediately after laser thermocoagulation were obtained to assess cystic duct occlusion. Animals were sacrificed for histopathologic correlation immediately after laser thermocoagulation (n = 4), 72 hr later (n = 4), and 6 weeks later (n = 15). RESULTS. In the in vitro studies, all 10 cystic ducts in the high-energy group were occluded, while only four in the low-energy group were occluded. At histology, all cases in both groups showed circumferential injury to the cystic duct wall without injury to the cystic artery or vein. In the in vitro experiments, the cystic duct was successfully cannulated in 21 (91%) of 23 animals. Cholangiography after thermocoagulation showed occlusion of the cystic duct in 16 (84%) of 19 cases. Immediately after laser thermocoagulation, the cystic duct mucosa was circumferentially destroyed, whereas after 72 hr necrosis of the cystic duct wall and periductal tissues had occurred. By 6 weeks, all pigs had complete cystic duct fibrosis without injury to the common bile duct. CONCLUSION. Holmium:yttrium-aluminum-garnet laser thermocoagulation of the cystic duct can be performed easily, results in immediate cystic duct occlusion, and leads to permanent fibrous ductal obliteration by 6 weeks.     

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.     

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...     

Effect of Rivastigmine on Mobility of Patients with Higher-Level Gait Disorder: A Pilot Exploratory Study

Background

Higher-level gait disorder (HLGD) in older adults is characterized by postural instability, stepping dysrhythmicity, recurrent falls and progressive immobility. Cognitive impairments are frequently associated with HLGD.

Objectives

The aim of this study was to compare gait and cognitive performance before and after the use of rivastigmine in patients with HLGD, free from cognitive impairment or Parkinsonism.

Methods

Fifteen non-demented patients with HLGD (age 79.2 ± 5.9 years; 11 women; Mini-Mental State Examination [MMSE] 28.3 ± 1.4) received escalating doses of rivastigmine for 12 weeks in an open-label, pilot study. They were assessed before and after treatment (week 0 and week 12), and after a 4-week washout period (week 16). Assessments included the Mindstreams computerized neuropsychological battery, Activities-specific Balance Confidence Scale, State-Trait Anxiety Inventory, Geriatric Depression Scale, Timed Up and Go (TUG) test, gait speed and stride time variability. One-way multiple analysis of variance tests for repeated measures were used, and Pillai’s trace test was considered as robust to investigate significant differences.

Results

The mean dose of rivastigmine during the 8–12 week period was 5.1 ± 2.3 mg/day. A positive effect was observed on the Mindstreams memory subscale and anxiety scores [Pillai’s trace: F(6,724) = 0.508, p = 0.010; and F(7,792) = 0.545, p = 0.006, respectively, over the course of the study] as well as on mobility (TUG test) [Pillai’s trace: F(4,863) = 0.448; p = 0.028], whereas gait speed and stride time variability did not change.

Conclusions

The use of relatively low-dose rivastigmine did not affect gait speed and stride time variability; however, the general mobility and anxiety were improved. These preliminary results warrant a larger, randomized, placebo-controlled study.