HPM Approximations for Trajectories: From a Golf Ball Path to Mercury’s Orbit

In this work, we propose the approximated analytical solutions for two highly nonlinear problems using the homotopy perturbation method (HPM). We obtained approximations for a golf ball trajectory model and a Mercury orbit’s model. In addition, to enlarge the domain of convergence of the first case study, we apply the Laplace-Padé resummation method to the HPM series solution. For both case studies, we were able to obtain approximations in good agreement with numerical methods, depicting the basic nature of the trajectories of the phenomena

GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively

A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease

Abstract: Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn’s disease (CD), some of which confer susceptibility to both diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases

Influence of insulin resistance status on the development of gallstones following roux-en-Y gastric bypass: a prospective cohort study

The occurrence of gallstones following Roux-en-Y gastric bypass (RYGB) has been extensively reported. As RYGB promotes improvement in insulin resistance (IR), which is one of the factors enrolled in the pathophysiology of gallstones, this study aims to determine the influence of IR and its post-RYGB course on the development of gallstones. This is a prospective cohort study that enrolled 108 morbidly obese subjects free of gallstones which underwent RYGB and were followed up for 24 months, through clinical, laboratory, and ultrasound examinations. IR was assessed through the surrogate marker homeostasis model assessment (HOMA). Of the individuals evaluated, 29 (26.8 %) developed gallstones following RYGB. In the univariate analysis, postsurgical gallstones were associated with preoperative HOMA (p < 0.0001), preoperative fasting glucose (p = 0.0019), preoperative fasting insulin (p = 0.0001), and preoperative triglycerides (p = 0.0001). Multivariate analysis revealed that preoperative HOMA was the only factor independently associated with gallstones (p < 0.0001). The incidence of gallstones among individuals with IR was 46.8 %; in the non-IR subjects, the incidence was 7.4 % (p < 0.0001). Preoperative IR led to a relative risk of 6.02 (95 % CI = 2.1-17.3; p = 0.0009) of gallstones. As gallstones often occur following RYGB, there is controversy regarding their management. Some authors propose systematic cholecystectomy along with RYGB, while others suggest that the aggregate risk of the concomitant approach is significantly higher. As IR was a significant risk factor in this study, an individualized approach for this population may be proposed. Further research is needed to confirm these findings.The occurrence of gallstones following Roux-en-Y gastric bypass (RYGB) has been extensively reported. As RYGB promotes improvement in insulin resistance (IR), which is one of the factors enrolled in the pathophysiology of gallstones, this study to determ264769775sem informaçãosem informaçã

Influence of the STAT3 genetic variants in the susceptibility to psoriatic arthritis and Behcet's disease

Pathophysiology and treatment of rheumatic disease