State-restricted adaptive control of a multilevel rotating electromagnetic mechanical flexible device using electromagnetic actuators.

This work presents the development of a multilevel electromagnetic actuation system that controls the shape of a flexible rotatory robotic structure. An array of electromagnets is used as the set of actuators that regulate the position of permanent magnets within the flexible device. The primary outcome of this study is the design and experimental validation of the multilevel rotating device. In addition, the theoretical description of the system motion under electromagnetic actuation is formulated using Euler-Lagrange and electromagnetic theories. Given the developed model, a theoretical study leads to designing an adaptive control that considers motion restrictions in the flexible device. The controller aims to modify the current applied to the electromagnets, which changes the interaction forces between the electromagnet and the permanent magnets in the robotic flexible structure. A set of numerical simulations confirms the proposed controller's effectiveness compared to the traditional state feedback approach that does not consider the state restrictions, which is implemented in devices that also operate under an electromagnetic approach. Furthermore, an experimental version of the flexible device allows for testing of the developed controller. The experimental results show the suitability of the proposed control to generate non-oscillatory controlled motion during the regulation of the flexible mechanic device shape.

Trajectory tracking control with state restricted gains for a magnetic pendulum using electromagnetic actuators.

Electromagnetic actuation results suitable for wireless driven motion, where the estimation of the force between magnetic elements is usually required. This force can lead to states where the magnetic-mechanical system remains fixed, requiring constraints to avoid the transgression of these states, and Barrier Lyapunov Functions (BLF) are useful for this purpose. This work presents an adaptive controller with BLF in a magnetic pendulum with state restrictions. It employs fixed electromagnets to induce motion on a pendulum with a permanent magnet as its bob. The force between the magnetic elements is obtained through approximation functions. A new implementation strategy for the control gains introduces the effect of state restrictions on the control action based on a control BLF. Results are analyzed in both simulations and experimental stages, which prove the advantages of employing BLF controllers in mechanical systems that require the avoidance of specific boundaries.

Exercise intervention does not reduce the likelihood of VO2max underestimation in older adults with hypertension.

The present study aimed to investigate whether training status would influence the capacity of a verification phase (VER) to confirm maximal oxygen uptake (VO2max) of a previous graded exercise test (GXT) in individuals with hypertension. Twelve older adults with hypertension (8 women) were recruited. Using a within-subject design, participants performed a treadmill GXT to exhaustion followed by a multistage VER both before and after a 12-wkcombined exercise training programme. Individual VO2max, respiratory exchange ratio (RER), maximal heart rate (HRmax), and rating of perceived exertion (RPE) were measured during both GXT and VER tests. Absolute and relative VO2max values were higher in VER than in GXT at baseline, but only absolute VO2max differed between bouts post-intervention (all p < 0.05). Individual VO2max comparisons revealed that 75% of the participants (9/12) achieved a VO2max value that was ≥3% during VER both before (range: +4.9% to +21%) and after the intervention (range: +3.4% to +18.8%), whereas 91.7% (11/12) of the tests would have been validated as a maximal effort if the classic criteria were employed. A 12-wk combined training intervention could not improve the capacity of older adults with hypertension to achieve VO2max during a GXT, as assessed by VER.

Maximal Oxygen Uptake Is Underestimated during Incremental Testing in Hypertensive Older Adults: Findings from the HAEL Study.

PURPOSE: The present cross-sectional study aimed to investigate whether a maximal oxygen uptake (V˙O2max) verification phase (VER) could improve the accuracy of a previous graded exercise test (GXT) to assess individual V˙O2max in hypertensive individuals. METHODS: Thirty-three older adults with hypertension (24 women) taking part in the Hypertension Approaches in the Elderly Study (NCT03264443) were recruited. Briefly, after performing a treadmill GXT to exhaustion, participants rested for 10 min and underwent a multistage VER to confirm GXT results. Individual V˙O2max, RER, maximal heart rate (HRmax), and RPE were measured during both GXT and VER tests. Mean values were compared between bouts using paired sample t-tests, and V˙O2max was also compared between GXT and VER on an individual basis. RESULTS: Testing was well tolerated by all participants. Both absolute (P = 0.011) and relative (P = 0.014) V˙O2max values were higher in VER than that in GXT. RER (P < 0.001) and RPE (P = 0.002) were lower in VER, whereas HRmax (P = 0.286) was not different between the two trials. Individual V˙O2max comparisons revealed that 54.6% of the participants (18/33) achieved a V˙O2max value that was ≥3% during VER (mean = 13.5%, range = +3% to +22.1%, ES = 0.062), whereas 87.9% (29/33) of the tests would have been validated as a maximal effort if the classic criteria were used (i.e., V̇O2 plateau or at least two secondary criteria). CONCLUSION: In sedentary older individuals with hypertension, GXT to exhaustion underestimated V˙O2max in more than half of tested participants, even when established, but criticized criteria were used to confirm whether a maximal effort was attained. Using VER after GXT is a quick approach to assist with the verification of an individual's V˙O2max.

Adaptive sliding-mode controller of a lower limb mobile exoskeleton for active rehabilitation.

This study describes the design, instrumentation and control of an exoskeleton for lower limb children rehabilitation with nine degrees of freedom. Three degrees of freedom in each leg exert the movements of hip, knee and ankle in the sagittal plane, and three control the drive track system composed by a caterpillar-like robot. The control scheme presents a model free decentralized output feedback adaptive high-order sliding mode control to solve the trajectory tracking problem in each degree of freedom of the exoskeleton. A high order sliding mode differentiator estimates the unmeasured states and, by means of a dynamical state extension, it approximates the unknown dynamical model of the exoskeleton. A second-order adaptive sliding mode controller based on the super-twisting algorithm drives the exoskeleton articulations to track the proposed reference trajectories, inducing an ultimate boundedness for the tracking error. Numerical and experimental simulation results demonstrate the effect of the adaptive gain on the super-twisting control design. Such evaluations confirmed the superior tracking performance forced by the adaptive law for the controller with a smaller chattering amplitude and smaller mean tracking error.

TGFBR1 intralocus epistatic interaction as a risk factor for colorectal cancer.

In colorectal cancer (CRC), an inherited susceptibility risk affects about 35% of patients, whereas high-penetrance germline mutations account for <6% of cases. A considerable proportion of sporadic tumors could be explained by the coinheritance of multiple low-penetrance variants, some of which are common. We assessed the susceptibility to CRC conferred by genetic variants at the TGFBR1 locus. We analyzed 14 polymorphisms and the allele-specific expression (ASE) of TGFBR1 in 1025 individuals from the Spanish population. A case-control study was undertaken with 504 controls and 521 patients with sporadic CRC. Fourteen polymorphisms located at the TGFBR1 locus were genotyped with the iPLEX Gold (MassARRAY-Sequenom) technology. Descriptive analyses of the polymorphisms and haplotypes and association studies were performed with the SNPator workpackage. No relevant associations were detected between individual polymorphisms or haplotypes and the risk of CRC. The TGFBR1*9A/6A polymorphism was used for the ASE analysis. Heterozygous individuals were analyzed for ASE by fragment analysis using cDNA from normal tissue. The relative level of allelic expression was extrapolated from a standard curve. The cutoff value was calculated with Youden's index. ASE was found in 25.4% of patients and 16.4% of controls. Considering both bimodal and continuous types of distribution, no significant differences between the ASE values of patients and controls were identified. Interestingly, a combined analysis of the polymorphisms and ASE for the association with CRC occurrence revealed that ASE-positive individuals carrying one of the most common haplotypes (H2: 20.7%) showed remarkable susceptibility to CRC (RR: 5.25; 95% CI: 2.547-5.250; p<0.001) with a synergy factor of 3.7. In our study, 54.1% of sporadic CRC cases were attributable to the coinheritance of the H2 haplotype and TGFBR1 ASE. These results support the hypothesis that the allelic architecture of cancer genes, rather than individual polymorphisms, more accurately defines the CRC risk.

Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. METHODS: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. RESULTS: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. CONCLUSIONS: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

The Int7G24A variant of transforming growth factor-beta receptor type I is a risk factor for colorectal cancer in the male Spanish population: a case-control study.

BACKGROUND: The Int7G24A variant of transforming growth factor-beta receptor type I (TGFBR1) has been shown to increase the risk for kidney, ovarian, bladder, lung and breast cancers. Its role in colorectal cancer (CRC) has not been established. The aims of this study were to assess the association of TGFBR1*Int7G24A variant with CRC occurrence, patient age, gender, tumour location and stage. METHODS: We performed a case-control study with 504 cases of sporadic CRC; and 504 non-cancerous age, gender and ethnically matched controls. Genotyping analysis was performed using allelic discrimination assay by real time PCR. RESULTS: The Int7G24A variant was associated with increased CRC incidence in an additive model of inheritance (P for trend = 0.005). No significant differences were found between Int7G24A genotypes and tumour location or stage. Interestingly, the association of the Int7G24A variant with CRC risk was significant in men (odds ratio 4.10 with 95% confidence intervals 1.41-11.85 for homozygous individuals; P for trend = 0.00023), but not in women. We also observed an increase in susceptibility to CRC for individuals aged less than 70 years. CONCLUSION: Our data suggest that the Int7G24A variant represents a risk factor for CRC in the male Spanish population.

The TGFBR1*6A allele is not associated with susceptibility to colorectal cancer in a Spanish population: a case-control study.

BACKGROUND: TGF-beta receptor type I is a mediator of growth inhibitory signals. TGFBR1*6A (rs11466445) is a common polymorphic variant of the TGF-beta receptor I gene and has been associated with tumour susceptibility. Nevertheless, the role of this polymorphism as a risk factor for colorectal cancer is controversial. The aim of this study was to assess the association between TGFBR1*6A and colorectal cancer, age, sex, tumour location and tumour stage in a Spanish population. METHODS: The case-control study involved 800 Spanish subjects: 400 sporadic colorectal cancer patients and 400 age-, sex-, and ethnic-matched controls. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated using unconditional logistic regression adjusted for age and sex. Analysis of somatic mutations at the GCG repeat of TGFBR1 exon 1 and germline allele-specific expression were also conducted to obtain further information on the contribution of the TGFBR1*6A allele to CRC susceptibility. RESULTS: There was no statistically significant association between the TGFBR1*6A allele and CRC (p > 0.05). The OR was 1.147 (95% CI: 0.799-1.647) for carriers of the TGFBR1*6A allele and 0.878 (95% CI: 0.306-2.520) for homozygous TGFBR1*6A individuals compared with the reference. The frequency of the polymorphism was not affected by age, sex or tumour stage. The TGFBR1*6A allele was more prevalent among colon tumour patients than among rectal tumour patients. Tumour somatic mutations were found in only two of 69 cases (2.9%). Both cases involved a GCG deletion that changed genotype 9A/9A in normal DNA to genotype 9A/8A. Interestingly, these two tumours were positive for microsatellite instability, suggesting that these mutations originated because of a deficient DNA mismatch repair system.Allele-specific expression of the 9A allele was detected in seven of the 14 heterozygous 9A/6A tumour cases. This could have been caused by linkage disequilibrium of the TGFBR1*6A allele with mutations that cause allele-specific expression, as was recently suggested. CONCLUSION: Our results suggest that the TGFBR1*6A allele does not confer an increased risk of colorectal cancer in the Spanish population.