Decentralized H

The design of the dynamic output feedback H∞ control for uncertain interconnected systems of neutral type is investigated. In the framework of Lyapunov stability theory, a mathematical technique dealing with the nonlinearity on certain matrix variables is developed to obtain the solvability conditions for the anticipated controller. Based on the corresponding LMIs, the anticipated gains for dynamic output feedback can be achieved by solving some algebraic equations. Also, the norm of the transfer function from the disturbance input to the controlled output is less than the given index. A numerical example and the simulation results are given to show the effectiveness of the proposed method

Singular Value Decomposition-Based Method for Sliding Mode Control and Optimization of Nonlinear Neutral Systems

The sliding mode control and optimization are investigated for a class of nonlinear neutral systems with the unmatched nonlinear term. In the framework of Lyapunov stability theory, the existence conditions for the designed sliding surface and the stability bound α∗ are derived via twice transformations. The further results are to develop an efficient sliding mode control law with tuned parameters to attract the state trajectories onto the sliding surface in finite time and remain there for all the subsequent time. Finally, some comparisons are made to show the advantages of our proposed method

Fecal microbiota transplantation in a child with severe ASD comorbidities of gastrointestinal dysfunctions—a case report

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors. In addition to behavioral interventions and psychotherapies, and pharmacological interventions, in-depth studies of intestinal microbiota in ASD has obvious abnormalities which may effectively influenced in ASD. Several attempts have been made to indicate that microbiota can reduce the occurrence of ASD effectively. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient’s gastrointestinal tract to improve the gut microenvironment. In this case report, we describe a case of child ASD treated by FMT. The patient have poor response to long-term behavioral interventions. After five rounds of FMT, clinical core symptoms of ASD and gastrointestinal(GI) symptoms were significantly altered. Moreover, the multiple levels of functional development of child were also significantly ameliorated. We found that FMT changed the composition of the intestinal microbiota as well as the metabolites, intestinal inflammatory manifestations, and these changes were consistent with the patient’s symptoms. This report suggests further FMT studies in ASD could be worth pursuing, and more studies are needed to validate the effectiveness of FMT in ASD and its mechanisms

Development and Application Effect of Knowledge-to-action Framework-based Health Management in Adolescents with Depressive Disorder in Remote Counties

BackgroundThe prevalence of depressive disorder in adolescents is increasing. Adolescents with depressive disorder in remote counties and their families have a low awareness of the disease, and often are difficult to complete the whole treatment.ObjectiveTo explore the application effect of knowledge-to-action (KTA) framework-based health management in adolescents with depressive disorder in remote counties.MethodsNinety-four adolescents with depressive disorder coming from remote countries were recruited from the Second Affiliated Hospital of Nanchang University from June to December 2020. They were randomly divided into a routine group (receiving a 12-week routine health management) and a KTA group (receiving a 12-week KTA framework-based health management) . At the time of enrollment and 12 weeks after intervention, the status of non-suicidal self-injury was assessed by the Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSAQ) , mobile phone use was evaluated by the Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) , the anxiety was evaluated with the score of the Screen for Child Anxiety Related Emotional Disorders (SCARED) , and the depression was assessed by the Depression Self-Rating Scale for Childhood (DSRS) .ResultsTwo groups had no significant differences in mean total scores of ANSAQ, SQAPMPU, SCARED, and DSRS before receiving intervention (P>0.05) .Two groups had no significant differences in each dimension score of SQAPMPU before receiving intervention (P>0.05) .After the 12-week intervention, the mean total scores of ANSAQ, SQAPMPU, SCARED, and DSRS decreased significantly in both groups (P<0.05) , and they were lowered more significantly in the KTA group (P<0.05) , the each dimension score of SQAPMPU decreased significantly in both groups (P<0.05) , and they were lowered more significantly in the KTA group (P<0.05) .ConclusionKTA framework-based health management could effectively reduce the incidence of non-suicidal self-injury and the problematic use rate of mobile phones, relieve the anxiety and depression in adolescents with depressive disorder in remote counties, indicating that this type of health management may have good applicability as an outpatient management in this group

Plan estratégico de la marca Biciklo para el ingreso al mercado limeño de bicicletas

Biciklo es una marca reconocida internacionalmente que ingresará al mercado limeño ofreciendo bicicletas de alta calidad e innovadoras a precios competitivos. La marca ingresará en tres segmentos: montaña con el modelo Montano, carrera con el modelo Speedo y recreación con el modelo Eskapi. Debido a la pandemia del Covid-19, el uso de bicicleta en Lima se ha intensificado. Biciklo busca ingresar al mercado de bicicletas de gama media-alta, el cual está cubierto en más del 50 % por una sola empresa. Mediante un sólido plan de marketing, la empresa busca posicionarse y alcanzar el 25 % del market share al quinto año. La inversión inicial para el funcionamiento de la empresa y la comercialización será de S/ 800,000. Se espera que las estrategias de marketing permitan contar con un crecimiento de ventas anual superior a 40 % en los primeros cinco años. El estudio de mercado demostró que existe una demanda en crecimiento para bicicletas de este tipo. Por ello, Biciklo se enfocará en un grupo de la población que está dispuesto a pagar más de S/ 2,000 por una bicicleta de calidad. Para el desarrollo del proyecto, Biciklo considera el personal mínimo indispensable, ya que se encuentra en una etapa inicial de operaciones; sin embargo, para la empresa es importante mantener un buen clima laboral y ofrecer línea de carrera a sus colaboradores a lo largo de los años. Para este proyecto, Biciklo está considerando como inversión inicial el monto de S/ 800,000, que casi en su totalidad será financiado por la casa matriz de Biciklo; se estima obtener un margen neto de utilidad promedio de 12 % en los primeros cinco años. Finalmente, los autores de esta investigación concluyen que Biciklo tiene una gran oportunidad de posicionarse en el mercado limeño

Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing

Background: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC. Methods: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium(TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls. Results: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants. Conclusions: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.Peer reviewe

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Breast tumors from CHEK2 1100delC-mutation carriers: genomic landscape and clinical implications

Introduction: Checkpoint kinase 2 (CHEK2) is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about twofold. We investigated gene copy-number aberrations and gene-expression profiles that are typical for breast tumors of CHEK2 1100delC-mutation carriers. Methods: In total, 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array-comparative genomic hybridization (aCGH) and gene-expression (GEX) experiments. After dimensionality reduction with CGHregions R package, CHEK2 1100delC-associated regions in the aCGH data were detected by the Wilcoxon rank-sum test. The linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by the bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC-related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2, and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3, and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors, nominating them as candidates for CHEK2 1100delC-associated tumor-progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM, and LRP1 on 12q13. Altogether, 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44, reduced expression levels. Our results suggest the WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC-mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC-associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy-number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions, we identified potential drivers of CHEK2 1100delC-associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene-expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of the CHEK2 1100delC mutation

ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk

PURPOSE: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT). EXPERIMENTAL DESIGN: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1-CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case-control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls. RESULTS: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)-like (N = 226). We then examined their association with breast cancer risk in the case-control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35-3.41), 1.57 (95% CI, 1.41-1.75), and 1.19 (95% CI, 1.08-1.31), respectively. The meta-analysis of population-specific datasets showed similar results. CONCLUSIONS: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Peer reviewe