Sulfasalazine attenuates ACL transection and medial menisectomy‐induced cartilage destruction by inhibition of cystine/glutamate antiporter

We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system ) expression. System uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system in OA is rarely addressed. Sulfasalazine (SSZ) is a system inhibitor; SSZ was applied intra‐articularly to study the function of system in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). Moerover, the system activator N‐acetylcysteine (NAC) was also applied to verify the role of system . The intra‐articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this effect was blocked by NAC. The results showed that inhibition of system function can attenuate ACLT + MMx‐induced cartilage destruction. In the present study, system inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT + MMx‐induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:650–657, 2016.     

Self‐triggered linear quadratic networked control

This paper deals with networked control systems design, under the constraint of limited bandwidth on the communication channel. A linear quadratic problem for a fixed sampling period is solved, and this result is used for the development of and performance indexes, yielding to the statement and solution of and optimal control problems. Finally, a self‐triggered controller is designed with a switched system approach in order to improve performance. Several examples are presented in order to illustrate the validity of the developed theory. Copyright © 2013 John Wiley & Sons, Ltd.     

In Vitro Evaluation of an Immediate Response Starling‐Like Controller for Dual Rotary Blood Pumps

Rotary ventricular assist devices (VADs) are used to provide mechanical circulatory support. However, their lack of preload sensitivity in constant speed control mode (CSC) may result in ventricular suction or venous congestion. This is particularly true of biventricular support, where the native flow‐balancing Starling response of both ventricles is diminished. It is possible to model the Starling response of the ventricles using cardiac output and venous return curves. With this model, we can create a Starling‐like physiological controller (SLC) for VADs which can automatically balance cardiac output in the presence of perturbations to the circulation. The comparison between CSC and SLC of dual HeartWare HVADs using a mock circulation loop to simulate biventricular heart failure has been reported. Four changes in cardiovascular state were simulated to test the controller, including a 700 reduction in circulating fluid volume, a total loss of left and right ventricular contractility, reduction in systemic vascular resistance ( ) from 1300 to 600 , and an elevation in pulmonary vascular resistance ( ) from 100 to 300 . SLC maintained the left and right ventricular volumes between 69–214 and 29–182 respectively, for all tests, preventing ventricular suction (ventricular volume = 0 ) and venous congestion (atrial pressures > 20 ). Cardiac output was maintained at sufficient levels by the SLC, with systemic and pulmonary flow rates maintained above 3.14 for all tests. With the CSC, left ventricular suction occurred during reductions in SVR, elevations in PVR, and reduction in circulating fluid simulations. These results demonstrate a need for a physiological control system and provide adequate in vitro validation of the immediate response of a SLC for biventricular support.     

Heritability of Thoracic Spine Curvature and Genetic Correlations With Other Spine Traits: The Framingham Study

Hyperkyphosis is a common spinal disorder in older adults, characterized by excessive forward curvature of the thoracic spine and adverse health outcomes. The etiology of hyperkyphosis has not been firmly established, but may be related to changes that occur with aging in the vertebrae, discs, joints, and muscles, which function as a unit to support the spine. Determining the contribution of genetics to thoracic spine curvature and the degree of genetic sharing among co‐occurring measures of spine health may provide insight into the etiology of hyperkyphosis. The purpose of our study was to estimate heritability of thoracic spine curvature using T₄–T₁₂ kyphosis (Cobb) angle and genetic correlations between thoracic spine curvature and vertebral fracture, intervertebral disc height narrowing, facet joint osteoarthritis (OA), lumbar spine volumetric bone mineral density (vBMD), and paraspinal muscle area and density, which were all assessed from computed tomography (CT) images. Participants included 2063 women and men in the second and third generation offspring of the original cohort of the Framingham Study. Heritability of kyphosis angle, adjusted for age, sex, and weight, was 54% (95% confidence interval [CI], 43% to 64%). We found moderate genetic correlations between kyphosis angle and paraspinal muscle area (_G, –0.46; 95% CI, –0.67 to –0.26), vertebral fracture (_G, 0.39; 95% CI, 0.18 to 0.61), vBMD (_G, –0.23; 95% CI, –0.41 to –0.04), and paraspinal muscle density (_G, –0.22; 95% CI, –0.48 to 0.03). Genetic correlations between kyphosis angle and disc height narrowing (_G, 0.17; 95% CI, –0.05 to 0.38) and facet joint OA (_G, 0.05; 95% CI, –0.15 to 0.24) were low. Thoracic spine curvature may be heritable and share genetic factors with other age‐related spine traits including trunk muscle size, vertebral fracture, and bone mineral density. © 2016 American Society for Bone and Mineral Research.     

A stochastic maximum principle for processes driven by G‐Brownian motion and applications to finance

On the basis of the theory of stochastic differential equations on a sublinear expectation space , we develop a stochastic maximum principle for a general stochastic optimal control problem, where the controlled state process is a stochastic differential equation driven by G‐Brownian motion. Furthermore, under some convexity assumptions, we obtain sufficient conditions for the optimality of the maximum in terms of the ‐function. Finally, applications of the stochastic maximum principle to the mean‐variance portfolio selection problem in the financial market with ambiguous volatility is discussed.     

New results on dynamic output feedback control for Markovian jump systems with time‐varying delay and defective mode information

This paper investigates the problem of delay‐dependent dynamic output feedback control for a class of discrete‐time Markovian jump linear systems (MJLSs). The systems under consideration are subject to time‐varying delay and defective mode information. The defective transition probabilities comprise of three types: exactly known, uncertain, and unknown. By employing a two‐term approximation for the time‐varying delay, the original MJLSs can be equivalently converted into a feedback interconnection form, which contains a forward subsystem with constant time‐delays and a feedback one with norm‐bounded uncertainties. Then, based on the scaled small‐gain theorem, the problem is therefore recast as an control problem in the face of uncertainties via an input–output framework. It is shown that the explicit expressions of the desired controller gains can be characterized in terms of strict linear matrix inequalities via some linearization techniques. Simulation studies are performed to illustrate the effectiveness and less conservatism of the proposed methods. Copyright © 2013 John Wiley & Sons, Ltd.     

New delay‐dependent exponential stability for neutral Markovian jump systems with mixed delays and nonlinear perturbations

This paper deals with the problem of delay‐dependent exponential stability for neutral Markovian jump systems with mixed delays and nonlinear perturbations. Based on Lyapunov stability theory and linear matrix inequality method, some new exponential stability criteria are presented. The difference between this paper and other existing results is that the lower bounds of the neutral delay, the upper bounds of the neutral delay and discrete delay are considered, which will obtain some less conservative stability analysis results. Numerical examples are given to show that the proposed criteria improve the existing results.     

Mixed and passive filtering for a class of singular systems with interval time‐varying delays

This paper deals with the problem of mixed and passive filtering for a class of singular systems with interval time‐varying delays. First, by combining the Wirtinger‐based integral inequality with the reciprocally convex inequality, sufficient delay‐range‐dependent conditions are obtained in terms of strict linear matrix inequalities to ensure that the considered singular system is admissible with a mixed and passivity performance level. Then, based on a matrix transformation technique and employing several free scalars, more flexible strict linear matrix inequality–based conditions are proposed to get the desired filter. Finally, 2 numerical examples are given to show less conservatism and the effectiveness of the results.     

H∞ filter design for linear time‐invariant systems with polytopic uncertainties in finite frequency domain

This paper deals with the problem of finite frequency full‐order filter design for discrete‐time and continuous‐time linear systems, with polytopic uncertainties. Based on the generalized Kalman–Yakubovich–Popov lemma and a parameter‐dependent Lyapunov function, a set of sufficient conditions are established in terms of matrix inequalities, ensuring that the filtering error system is stable and the attenuation level, from disturbance to the estimation error, is smaller than a given value over a prescribed finite frequency domain of the external disturbances. Then, in order to linearize and relax the obtained matrix inequalities, we introduce a large number of slack variables by applying Finsler's lemma twice, which provides extra degrees of freedom in optimizing the guaranteed performance. This leads to performance improvement and reduction of conservatism in the solution. It is shown later that the robust filter gains can be obtained by solving a set of linear matrix inequalities. Numerical examples are given to illustrate the effectiveness and the less conservatism of the proposed approach in comparison with the existing methods. Copyright © 2016 John Wiley & Sons, Ltd.     

High level of intracellular sperm oxidative stress negatively influences embryo pronuclear formation after intracytoplasmic sperm injection treatment

This study evaluates the relationship between sperm intracellular reactive oxygen species (ROS; H₂O₂, O₂), DNA fragmentation (DF), low mitochondria membrane potential (MMP) of sperm and normal pronuclear formation among intracytoplasmic sperm injection (ICSI) patients. Semen samples were obtained from 62 infertile male who were candidates for ICSI treatment. After sperm processing, metaphase II (MII) oocytes were injected, and the mean percentages of intracellular ROS, MMP and DF were evaluated using flow cytometry. The mean percentages of pronuclear formation and zygote score (Z) were also recorded, and Pearson, Spearman's rank correlation coefficient and Kruskal–Wallis tests were applied to analyse the data. The amounts of sperm intracellular H₂O₂ and ˙ had significant positive correlation with low MMP (P < 0.01). The intracellular ROS had a negative correlation with pronuclear formation (P < 0.05), and its effect was higher than 66.66%. In addition, the mean percentages of neither H₂O₂ nor ˙ affected the quality of pronuclear embryos (Z‐score). This study shows that although high levels of both sperm intracellular H₂O₂ and ˙ in ICSI patients have deleterious effect on sperm MMP, only H₂O₂ may interfere in pronuclear formation.     

Robust observer‐based control for uncertain discrete time‐delay systems with nonlinearities electric‐hydraulic system under Hölder condition

In this paper, the robustness and control problems of output dynamic observer‐based control for uncertain discrete time‐delay systems with nonlinearities under a class of Hölder condition are considered. The parameter uncertainties enter into all the system matrices, the time‐varying delay is unknown with given lower and upper bounds, and the nonlinearities are described by satisfying a class of α Hölder condition. The asymptotic stabilization for uncertain time‐delay nonlinear system will be guaranteed. Linear matrix inequality optimization approach is used to design the robust observer‐based output dynamic controls. The feedback control and observer gains are got from linear matrix inequality optimization feasible solution. Electric‐hydraulic system is described and used to illustrate the method.     

The association of peri‐operative scores,including frailty,with outcomes after unscheduled surgery

Postoperative hospital stay is longer for frail, older patients, who are more likely to experience prolonged postoperative morbidity and reduced long‐term survival. We recorded in‐hospital mortality, morbidity and length of stay for 164 patients aged at least 65 years after unscheduled surgery. We evaluated pre‐operative frailty with the 7‐point Clinical Frailty Scale: 81 patients were ‘not vulnerable’ (frailty score 1–3) and 83 were ‘vulnerable or frail’ (frailty score 4), with mean (SD) ages of 74.7 (7.5) years vs. 79.4 (8.3) years, respectively, p < 0.001. Within 30 postoperative days 8/164 (5%) patients died, all with frailty scores 4, p = 0.007. Postoperative morbidity was less frequent in patients categorised as ‘not vulnerable’ on four out of the six days it was measured (days 3, 5, 8, 14, 23, 28). Median (IQR [range]) postoperative stay was 9 (6–18 [2–221]) days for patients with frailty scores 1–3, and 22 (12–33 [2–270]) days for patients with score 4, p < 0.001. Four variables independently associated with hospital discharge, hazard ratio (95%CI): E‐POSSUM, 0.74 (0.60–0.92), p = 0.007; ASA 2, 0.35 (0.13–0.98), p = 0.046, ASA 3, 0.17 (0.06–0.47), p = 0.001 and ASA 4/5, 0.08 (0.02–0.28), p < 0.001; operative severity ‘major +’, 0.69 (0.41–1.08), p = 0.10 and the Surgical Outcome Risk Tool, 7.75 (0.81–74.40), p = 0.08.     

Symptoms of Posttraumatic Stress Rather Than Mild Traumatic Brain Injury Best Account for Altered Emotional Responses in Military Veterans

Emotional dysfunction is evident in posttraumatic stress disorder (PTSD), yet it is unclear what aspects of the disorder most directly relate to aberrant emotional responding. Also, the frequent co‐occurrence of blast‐related mild traumatic brain injuries (mTBIs) among recently deployed U.S. military personnel complicates efforts to understand the basis for emotional disruption. We studied a cross‐sectional sample (enriched for PTSD and mTBI) of 123 U.S. veterans of wars in Iraq and Afghanistan. We measured subjective affective evaluations and peripheral psychophysiological responses to images with pleasant, neutral, unpleasant, and combat‐related aversive content. When compared with other postdeployment participants, those who had combat‐related PTSD rated pleasant image content as less positive ( = .04) and less arousing ( = .06), and exhibited heightened physiological responsivity to combat image content ( = .07). Symptoms of PTSD were associated with elevated skin conductance responses (β = .28), reduced heart rate deceleration (β = .44 to .47), and increased corrugator facial muscle electromyography (β = .47). No effects for blast‐related mTBI were observed across any affective modulation measures. These findings point to a greater impact of PTSD symptomatology than blast‐related mTBI on emotional functioning and highlight the utility of dimensional assessments of psychopathology for understanding the effects of combat‐stress conditions on adjustment to civilian life.     

Effect of the age of broodstock males on sperm function during cold storage in the trout (Oncorhynchus mykiss)

The knowledge of sperm quality in the broodstock males of different ages is a prerequisite to identify the reproductive ability of cultivated fish for the hatchery management. Thus, in this work, we analysed sperm function of the semen stored of broodstock males of rainbow trout (Oncorhychus mykiss) in different reproductive ages (2, 3 and 4 years old). Sperm samples of each reproductive age were stored in Storfish^® during 10 days at 4°C, and then, motility, viability, mitochondrial function (MMP), superoxide anion () level and DNA fragmentation (DNA_frag) were assessed. The results demonstrated that sperm function parameters were affected significantly by the age of the males and the time of storage. Motility, viability and MMP significantly decreased, and DNA_frag and level increased with the age increment and the time of storage. In conclusion, sperm quality of 2 and 3 years old were superior to those of 4 years old, based on higher quality of various sperm functions such as motility, viability, MMP, DNA integrity and level during short‐term storage. This information must be considered for optimum utilization of broodstock males in aquaculture.     

Attention Bias Variability and Symptoms of Posttraumatic Stress Disorder

Cognitive theories implicate information‐processing biases in the etiology of anxiety disorders. Results of attention‐bias studies in posttraumatic stress disorder (PTSD) have been inconsistent, suggesting biases towards and away from threat. Within‐subject variability of attention biases in posttraumatic patients may be a useful marker for attentional control impairment and the development of posttrauma symptoms. This study reports 2 experiments investigating threat‐related attention biases, mood and anxiety symptoms, and attention‐bias variability following trauma. Experiment 1 included 3 groups in a cross‐sectional design: (a) PTSD, (b) trauma‐exposed without PTSD, and (c) healthy controls with no trauma or Axis I diagnoses. Greater attention‐bias variability was found in the PTSD group compared to the other 2 groups ; attention‐bias variability was significantly and positively correlated (r = .37) with PTSD symptoms. Experiment 2 evaluated combat‐exposed and nonexposed soldiers before and during deployment. Attention‐bias variability did not differentiate groups before deployment, but did differentiate groups during deployment ; increased variability was observed in groups with acute posttraumatic stress symptoms and acute depression symptoms only. Attention‐bias variability could be a useful marker for attentional impairment related to threat cues associated with mood and anxiety symptoms after trauma exposure.     

control of LPV systems with saturating actuators: Pólya approach

This paper addresses the design problem of , gain‐scheduling non‐linear state‐feedback controller for linear parameter varying (LPV) systems, subjected to actuator saturations and bounded energy disturbances, by using parameter‐dependent type Lyapunov functions. The paper provides a systematic procedure to generate a sequence of linear matrix inequality (LMI) type conditions of increasing precision for obtaining a suboptimal state‐feedback controller. The presented method utilizes the modified sector condition for formalization of actuator saturation and homogeneous polynomial parameter‐dependent representation of LPV systems. Both simulations and experimental studies on an inverted pendulum on a cart system illustrate the benefits of the approach. Copyright © 2011 John Wiley & Sons, Ltd.     

Robustness properties preservation in suboptimal T1DM H∞ control: ω‐SPR substitutions

Suboptimal controllers have been proposed to deal with robust glucose regulation problem at type 1 diabetic patients. The features of such controllers involve robust stability and robust performance. These suboptimal controllers are designed at a specific frequencies response, which corresponds to a diabetic type 1 under specific physiological conditions. An open problem stands for preservation of the robustness controller properties for a different frequencies interval beyond the used for designing. This problem is motivated by the possibility of finding distinct frequency response at T1DM patients around the world or under different physiological conditions. In this contribution, the SPR functions are exploited to analyze the robust stability and robust performance preservation. This analysis is done for each one transfer function in closed‐loop related to intake; our results are relevant because of the design range of the controllers can be extended which means that the controllers can be used on the patients with different physiological conditions.     

Bone Volume Fraction and Fabric Anisotropy Are Better Determinants of Trabecular Bone Stiffness Than Other Morphological Variables

As our population ages, more individuals suffer from osteoporosis. This disease leads to impaired trabecular architecture and increased fracture risk. It is essential to understand how morphological and mechanical properties of the cancellous bone are related. Morphology‐elasticity relationships based on bone volume fraction (BV/TV) and fabric anisotropy explain up to 98% of the variation in elastic properties. Yet, other morphological variables such as individual trabeculae segmentation (ITS) and trabecular bone score (TBS) could improve the stiffness predictions. A total of 743 micro–computed tomography (μCT) reconstructions of cubic trabecular bone samples extracted from femur, radius, vertebrae, and iliac crest were analyzed. Their morphology was assessed via 25 variables and their stiffness tensor () was computed from six independent load cases using micro finite element (μFE) analyses. Variance inflation factors were calculated to evaluate collinearity between morphological variables and decide upon their inclusion in morphology‐elasticity relationships. The statistically admissible morphological variables were included in a multiple linear regression model of the dependent variable . The contribution of each independent variable was evaluated (ANOVA). Our results show that BV/TV is the best determinant of (r²_adj = 0.889), especially in combination with fabric anisotropy (r²_adj = 0.968). Including the other independent predictors hardly affected the amount of variance explained by the model (r²_adj = 0.975). Across all anatomical sites, BV/TV explained 87% of the variance of the bone elastic properties. Fabric anisotropy further described 10% of the bone stiffness, but the improvement in variance explanation by adding other independent factors was marginal (<1%). These findings confirm that BV/TV and fabric anisotropy are the best determinants of trabecular bone stiffness and show, against common belief, that other morphological variables do not bring any further contribution. These overall conclusions remain to be confirmed for specific bone diseases and postelastic properties. © 2015 American Society for Bone and Mineral Research.     

Local low‐dose lovastatin delivery improves the bone‐healing defect caused by Nf1 loss of function in osteoblasts

Postfracture tibial nonunion (pseudoarthrosis) leads to lifelong disability in patients with neurofibromatosis type I (NF1), a disorder caused by mutations in the NF1 gene. To determine the contribution of NF1 in bone healing, we assessed bone healing in the Nf1 conditional mouse model lacking Nf1 specifically in osteoblasts. A closed distal tibia fracture protocol and a longitudinal study design were used. During the 21‐ to 28‐day postfracture period, callus volume, as expected, decreased in wild‐type but not in Nf1 mice, suggesting delayed healing. At these two time points, bone volume (BV/TV) and volumetric bone mineral density (vBMD) measured by 3D micro–computed tomography were decreased in Nf1 callus‐bridging cortices and trabecular compartments compared with wild‐type controls. Histomorphometric analyses revealed the presence of cartilaginous remnants, a high amount of osteoid, and increased osteoclast surfaces in Nf1 calluses 21 days after fracture, which was accompanied by increased expression of osteopontin, Rankl, and Tgfβ. Callus strength measured by three‐point bending 28 days after fracture was reduced in Nf1 versus wild‐type calluses. Importantly, from a clinical point of view, this defect of callus maturation and strength could be ameliorated by local delivery of low‐dose lovastatin microparticles, which successfully decreased osteoid volume and cartilaginous remnant number and increased callus BV/TV and strength in mutant mice. These results thus indicate that the dysfunctions caused by loss of Nf1 in osteoblasts impair callus maturation and weaken callus mechanical properties and suggest that local delivery of low‐dose lovastatin may improve bone healing in NF1 patients. © 2010 American Society for Bone and Mineral Research