Study of Seismic Base Isolation of Bridge Considering Soil Structure Interaction

In this paper, a comprehensive study of seismic response of base isolated bridge is made by varying different parameters such as soil stiffness, embedment depth, hydrodynamic pressure and earthquake response spectrum. The object is to determine effect of soil-structure interaction on seismic response when isolation by elastomeric bearing is provided between superstructure and substructure. Elastomeric bearing is seen to be effective in reducing seismic response of substructure on rocky site. The increase in embedment depth also causes reduction in bending moments and shear forces in the substructure. The use of elastomeric bearing in place of Rocker-Roller bearing is seen to be beneficial from seismic considerations

A comparative clinical study of two source plant Motha (Cyprus Rotundus Linn.) and Nagarmotha (Cyprus Scariousus) in Sthaulya (Obeisty)

Herbal product market is increasing day by day throughout the world and various pharmaceutical companies conducting extensive research on plant material for their potential medicinal value. Motha (Cyperus rotundus), a is found in all tropical, subtropical and temperate region of the world, in India its commonly known as Motha and its in cypereacea and Nagarmotha (Cyperus Scariosus) is pestiferous perennial, delicate slender sedge found wildly in various parts of the country, especially in damp or marshy areas and collected wildly for extraction of its essential oil using steam distillation. The present review article provide an overview on comparative clinical study done on Sthaulya (Obesity)

A decision support model for identification and prioritization of key performance indicators in the logistics industry

YesPerformance measurement of logistics companies is based upon various performance indicators. Yet, in the logistics industry, there are several vaguenesses, such as deciding on key indicators and determining interrelationships between performance indicators. In order to resolve these vaguenesses, this paper first presents the stakeholder-informed Balanced Scorecard (BSC) model, by incorporating financial (e.g. cost) and non-financial (e.g. social media) performance indicators, with a comprehensive approach as a response to the major shortcomings of the generic BSC regarding the negligence of different stakeholders. Subsequently, since the indicators are not independent of each other, a robust multi-criteria decision making technique, the Analytic Network Process (ANP) method is implemented to analyze the interrelationships. The integration of these two techniques provides a novel way to evaluate logistics performance indicators from logisticians' perspective. This is a matter that has not been addressed in the logistics industry to date, and as such remains a gap that needs to be investigated. Therefore, the proposed model identifies key performance indicators as well as various stakeholders in the logistics industry, and analyzes the interrelationships among the indicators by using the ANP. Consequently, the results show that educated employee (15.61%) is the most important indicator for the competitiveness of logistics companies

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

A comparative clinical study of two source plant Motha (Cyprus Rotundus Linn) and Nagarmotha (Cyprus Scariousus) in Sthaulya (Obeisty)

Herbal product market is increasing day by day throughout the world and various pharmaceutical companies conducting extensive research on plant material for their potential medicinal value. Motha (Cyperus rotundus), a is found in all tropical, subtropical and temperate region of the world, in India its commonly known as Motha and its in cypereacea. & Nagarmotha (Cyperus Scariosus) is pestiferous perennial, delicate slender sedge found wildly in various parts of the country, especially in damp or marshy areas and collected wildly for extraction of its essential oil using steam distillation. The present review article provide an overview on comparative clinical study done on Sthaulya (Obesity)

Management of transfusion needs in a case of immunizing anti-M antibody in a patient with acute myeloid leukemia

Anti-M is a relatively common "naturally occurring" antibody. Unexpected alloantibodies in patient's serum other than ABO isoagglutinins (e.g., anti-M) may cause a discrepancy in the reverse grouping. As long as anti-M does not react at 37°C, it is clinically insignificant for transfusion. However, we found this antibody to be of "immunizing" type which was reactive at 37°C and AHG phase and showing problems in blood grouping and crossmatch. This antibody had both IgM and IgG components. When "M" antibodies active at 37°C are encountered, antigen-negative or red cells that are compatible with an indirect antiglobulin test should be provided