A refined gravity model from Lageos (GEM-L2)

For abstract for A83-1354

Clinical correlates of blood-derived circulating tumor DNA in pancreatic cancer.

BackgroundTreatment outcomes for patients with advanced pancreatic ductal adenocarcinoma (PDAC) remain dismal. There are unmet needs for understanding the biologic basis of this malignancy using novel next-generation sequencing technologies. Herein, we investigated the clinical utility of circulating tumor DNA (ctDNA) (the liquid biopsy) in this malignancy.MethodsctDNA was analyzed in 112 patients with PDAC (54-73 genes) and tissue DNA in 66 patients (315 genes) (both clinical-grade next-generation sequencing). Number of alterations, %ctDNA, concordance between ctDNA and tissue DNA, and correlation of ctDNA results with survival were assessed.ResultsThe most common genes altered in ctDNA were TP53 (46% of patients, N = 51) and KRAS (44%, N = 49). Median number of characterized ctDNA alterations per patient was 1 (range, 0-6), but patients with advanced PDAC had significantly higher numbers of ctDNA alterations than those with surgically resectable disease (median, 2 versus 0.5, P = 0.04). Overall, 75% (70/94) of advanced tumors had ≥ 1 ctDNA alteration. Concordance rate between ctDNA and tissue DNA alterations was 61% for TP53 and 52% for KRAS. Concordance for KRAS alterations between ctDNA and tissue DNA from metastatic sites was significantly higher than between ctDNA and primary tumor DNA (72% vs 39%, P = 0.01). Importantly, higher levels of total %ctDNA were an independent prognostic factor for worse survival (hazard ratio, 4.35; 95% confidence interval, 1.85-10.24 [multivariate, P = 0.001]). A patient with three ctDNA alterations affecting the MEK pathway (GNAS, KRAS, and NF1) attained a response to trametinib monotherapy ongoing at 6 months.ConclusionsOur findings showed that ctDNA often harbored unique alterations some of which may be targetable and that significantly greater numbers of ctDNA alterations occur in advanced versus resectable disease. Furthermore, higher ctDNA levels were a poor prognostic factor for survival

Changes in murine anorectum signaling across the life course

Background: Increasing age is associated with an increase in the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to these conditions is not fully understood. This study examined the effects of increasing age on the function of the murine anorectum.Methods: The effects of increasing age on cholinergic, nitrergic, and purinergic signaling pathways in the murine anorectum were examined using classical organ bath assays to examine tissue function and electrochemical sensing to determine age‐related changes in nitric oxide and acetylcholine release.Key Results: Nitrergic relaxation increased between 3 and 6 months, peaked at 12 months and declined in the 18 and 24 months groups. These changes were in part explained by an age‐related decrease in nitric oxide (NO) release. Cholinergic signaling was maintained with age by an increase in acetylcholine (ACh) release and a compensatory decrease in cholinesterase activity. Age‐related changes in purinergic relaxation were qualitatively similar to nitrergic relaxation although the relaxations were much smaller. Increasing age did not alter the response of the anorectum smooth muscle to exogenously applied ACh, ATP, sodium nitroprusside or KCl. Similarly, there was no change in basal tension developed by the anorectum.Conclusions and Inferences: The decrease in nitrergic signaling with increasing age may contribute to the age‐related fecal impaction and constipation previously described in this model by partially obstructing defecation

Predicting the effectiveness of hepatitis C virus neutralizing antibodies by bioinformatic analysis of conserved epitope residues using public sequence data

Hepatitis C virus (HCV) is a global health issue. Although direct-acting antivirals are available to target HCV, there is currently no vaccine. The diversity of the virus is a major obstacle to HCV vaccine development. One approach toward a vaccine is to utilize a strategy to elicit broadly neutralizing antibodies (bNAbs) that target highly-conserved epitopes. The conserved epitopes of bNAbs have been mapped almost exclusively to the E2 glycoprotein. In this study, we have used HCV-GLUE, a bioinformatics resource for HCV sequence data, to investigate the major epitopes targeted by well-characterized bNAbs. Here, we analyze the level of conservation of each epitope by genotype and subtype and consider the most promising bNAbs identified to date for further study as potential vaccine leads. For the most conserved epitopes, we also identify the most prevalent sequence variants in the circulating HCV population. We examine the distribution of E2 sequence data from across the globe and highlight regions with no coverage. Genotype 1 is the most prevalent genotype worldwide, but in many regions, it is not the dominant genotype. We find that the sequence conservation data is very encouraging; several bNAbs have a high level of conservation across all genotypes suggesting that it may be unnecessary to tailor vaccines according to the geographical distribution of genotypes

Characteristics of Fatal Cases of Pandemic Influenza A (H1N1) from September 2009 to January 2010 in Saurashtra Region, India

Background: India reported first case of 2009 pandemic influenza A (H1N1) virus infection in May, 2009 and Saurashtra region in August, 2009. We describe the characteristics of fatal cases of 2009 influenza A (H1N1) infection reported in Saurashtra region. Methods: From September, 2009 to January, 2010, we observed 71 fatal cases that were infected with 2009 influenza A (H1N1) virus and admitted in different hospitals in Rajkot city. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection; the clinico-epidemiological features were observed and documented. Results: Median age of the deceased (71) was 29 years, and 57.7% were females. Median time observed was 5 days from onset of illness to diagnosis of influenza A (H1N1), and 57.7% were referred from general practitioner (OR=0.42, CI=0.24-0.74). Median hospital stay reported was 3 days. All admitted patients received oseltamivir, but only 16.9% received it within 2 days of onset of illness. The most common symptoms were cough (97.2%), fever (93%), sore throat and shortness of breath. Co-morbid conditions were present in almost half of the patients who ultimately died, the most common of which was pregnancy (OR=0.15, CI=0.04-0.52). Radiological pneumonia was reported in 98% patients. Conclusion: Residing in urban area, delayed referral from general practitioner, presence of co-existing condition, especially pregnancy was responsible for mortality among influenza A (H1N1) infected positive

A Study to Compare Major Adverse Cardiac Event in Patient Undergoing PCI with Drug Eluting Stents Vs Bare Metal Stents

This study compared Major Adverse Cardiac Event in patient with Acute Coronary Syndromes undergoing PCI with Drug Eluting Stents Vs Bare Metal Stents. A retrospective, observational study was carried out in an inpatient setting of the private tertiary care hospital. Patients with >18 years, diagnosed for Acute Coronary Syndromes (ACS), required intervention in coronary artery with implantation of Drug Eluting Stents (DES) or Bare Metal Stents (BMS) were recruited in the study. The data had been collected from file or database of the hospital. All subjects were followed for major adverse cardiac event. Result. A total of 202 patients who underwent percutaneous coronary intervention (PCI) were enrolled into DES group (N=101) and BMS group (N=101). All patients were followed up at 1 month, 3 months, 6 months & 12 months for Major Adverse Cardiac Events (MACE). Clinical outcomes during 12 months were compared between DES group & BMS group. There was no significant difference in baseline parameters including demographic, risk factors of ACS, diagnosis, angiographic parameters between both groups. Overall MACE rates were reported non-significantly high in BMS group patients (14.85%) compare to DES group patients (8.91%) (P=0.458). However, DES group had lower rates of death (0.99% vs 1.98%, P=0.57), rate of MI (3.96% vs 4.95% P=0.73), rate of revascularization (1.98% vs 3.96% p=0.42) & rate of sub acute thrombosis (1.98% vs 3.96% P=0.42) and higher rate of bleeding (1.98% vs 0.99% p=0.57) compare to cohort-II. Conclusion. The use of DES in the setting of Acute Coronary Syndrome is associated with lower Major Adverse Cardiac Event (MACE) rate compared to BMS without compromising the overall safety over the course of one-year follow-up. The long-term safety of drug-eluting stents needs to be ascertained in large, randomized trials

Effect of metabolized polyethylene terephthalate, vacuum packaging and storage temperature on shelf life of papaya pulp Kalakand (Indian cookie)

The dairy plants are looking for newer products for diversification and value addition. There is scope for the dairy industry to introduce newer products as healthy, convenience and ready to eat foods for capacity utilization and value addition, but because of complex biochemical composition and high water content, milk and milk products act as an excellent culture medium for growth and multiplication of varieties of microorganisms. Vacuum packaging reduces product shrinkage, trim losses by eliminating oxidation and freezer burn resulting it can enhance product quality. Now a day metabolized polyethylene terephthalate (MET PET) with vacuum packaging have a promising role in storage of various value added milk product. The developed value added Kalakand product (Indian cookie) could be stored successfully for 5 days in MET PET packaging material at 4±1°C and when the product was packaged under vacuum the shelf life increased up to 10 days at 4±1°C