A CLINICAL STUDY ON THE EFFICACY OF VASA PRATISARANEEYA TEEKSHNA KSHARA IN THE MANAGEMENT OF ABHAYANTARA ARSHA/HAEMORRHOID

Astamahagda, group of eight dreadful clinical conditions told in all Ayurvedic classics. Aacharya Sushruta enlisted Arsha in Astamahagada. Arsha is known as haemorrhoids in modern parlance. The altered lifestyle in this modern world is the leading cause in the incidence of Haemorrhoids (Arshas). Symptoms of internal haemorrhoids closely resemble to clinical features of Abhyantara Arshas. Aacharya Shusruta described four types of treatment modalities for the management of Arsha, they are Bheshaja Karma, Kshara Karma, Agni Karma and Shastra Karma. Kshara is one of the most essential methods that can be used safely. An attempt has been made in this study to test the effectiveness of Vasa Pratisaraneeya Teekshna Kshara in the management of Abhayantra Arsha. In this study, 15 patients suffering from Abhyantra Arsha were selected from OPD and IPD of the PG Department of Shalya Tantra, NIA, Jaipur. The data obtained have been statistically analyzed and it has been observed that Kshara Karma is effective in curing the disease, preventing recurrence and cost-effective Para-surgical procedure. The outcome of Kshara Karma interference is motivating

Magnetic Proximity induced efficient charge-to-spin conversion in large area PtSe2_{2}/Ni80_{80}Fe20_{20} heterostructures

As a topological Dirac semimetal with controllable spin-orbit coupling and conductivity, PtSe$_2$, a transition-metal dichalcogenide, is a promising material for several applications from optoelectric to sensors. However, its potential for spintronics applications is yet to be explored. In this work, we demonstrate that PtSe$_{2}$/Ni$_{80}$Fe$_{20}$ heterostructure can generate a large damping-like current-induced spin-orbit torques (SOT), despite the absence of spin-splitting in bulk PtSe$_{2}$. The efficiency of charge-to-spin conversion is found to be $(-0.1 \pm 0.02)$~nm$^{-1}$ in PtSe$_{2}$/Ni$_{80}$Fe$_{20}$, which is three times that of the control sample, Ni$_{80}$Fe$_{20}$/Pt. Our band structure calculations show that the SOT due to the PtSe$_2$ arises from an unexpectedly large spin splitting in the interfacial region of PtSe$_2$ introduced by the proximity magnetic field of the Ni$_{80}$Fe$_{20}$ layer. Our results open up the possibilities of using large-area PtSe$_{2}$ for energy-efficient nanoscale devices by utilizing the proximity-induced SOT.Comment: 18 pages, 4 figure

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Discovery and Fine-Mapping of Adiposity Loci Using High Density Imputation of Genome-Wide Association Studies in Individuals of African Ancestry: African Ancestry Anthropometry Genetics Consortium

Genome-wide association studies (GWAS) have identified \u3e 300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P \u3c 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (\u3c5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P \u3c 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations

Assessing the impact of closely-spaced intersections on traffic operations and pollutant emissions on a corridor level

Traffic lights or roundabouts along corridors are usually installed to address location-specific operational needs. An understanding of the impacts on traffic regarding to highly-congested closely-spaced intersections has not been fully addressed. Accordingly, consideration should be given to how these specific segments affect corridor performance as a whole. One mixed roundabout/traffic light/stop-controlled junctions corridor was evaluated with the microscopic traffic model (VISSIM) and emissions methodology (Vehicle Specific Power – VSP). The analysis was focused on two major intersections of the corridor, a roundabout and a traffic light spaced lower than 170 m apart under different traffic demand levels. The traffic data and corridor geometry were coded into VISSIM and compared with an alternative scenario where the traffic light was replaced by a single-lane roundabout. This research also tested a method to improve corridor performance and emissions by examining the integrated effect of the spacing between these intersections on traffic delay and vehicular emissions (carbon dioxide, monoxide carbon, nitrogen oxides, and hydrocarbons). The Fast Non-Dominated Sorting Genetic Algorithm (NSGA-II) was used to find the optimal spacing for these intersections. The analysis showed that the roundabout could achieve lower queue length (∼64%) and emissions (16–27%, depending on the pollutant) than the traffic light. The results also suggested that 200 m of spacing using the best traffic control would provide a moderate advantage in traffic operations and emissions as compared with the existing spacing

Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)–Positive Metastatic Breast Cancer. A Randomized Clinical Trial

IMPORTANCE Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)–positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. OBJECTIVE To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, randomized, parallel-group, phase 3 equivalence study in patients with metastatic breast cancer. From December 2012 to August 2015, 500 patients were randomized 1:1 to receive a proposed biosimilar or trastuzumab plus a taxane. Chemotherapy was administered for at least 24 weeks followed by antibody alone until unacceptable toxic effects or disease progression occurred. INTERVENTIONS Proposed biosimilar (n = 230) or trastuzumab (n = 228) with a taxane. MAIN OUTCOMES AND MEASURES The primary outcome was week 24 overall response rate (ORR) defined as complete or partial response. Equivalence boundaries were 0.81 to 1.24 with a 90% CI for ORR ratio (proposed biosimilar/trastuzumab) and −15% to 15% with a 95% CI for ORR difference. Secondary outcome measures included time to tumor progression, progression-free and overall survival at week 48, and adverse events. RESULTS Among 500 women randomized, the intention-to-treat population included 458 women (mean [SD] age, 53.6 [11.11] years) and the safety population included 493 women. The ORR was 69.6% (95% CI, 63.62%-75.51%) for the proposed biosimilar vs 64.0% (95% CI, 57.81%-70.26%) for trastuzumab. The ORR ratio (1.09; 90% CI, 0.974-1.211) and ORR difference (5.53; 95% CI, −3.08 to 14.04) were within the equivalence boundaries. At week 48, there was no statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor progression (41.3% vs 43.0%; −1.7%; 95% CI, −11.1% to 6.9%), progression-free survival (44.3% vs 44.7%; −0.4%; 95% CI, −9.4% to 8.7%), or overall survival (89.1% vs 85.1%; 4.0%; 95% CI, −2.1% to 10.3%). In the proposed biosimilar and trastuzumab groups, 239 (98.6%) and 233 (94.7%) had at least 1 adverse event, the most common including neutropenia (57.5% vs 53.3%), peripheral neuropathy (23.1% vs 24.8%), and diarrhea (20.6% vs 20.7%). CONCLUSIONS AND RELEVANCE Among women with ERBB2-positive metastatic breast cancer receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess safety and long-term clinical outcome. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02472964; EudraCT Identifier: 2011-001965-4

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations