Publications by authors named "T V R K Murthy"

Background: Slow gastric emptying occurs frequently during critical illness and is roughly quantified at bedside by large gastric residual volumes (GRVs). A previously published trial (The Augmented versus Routine approach to Giving Energy Trial; TARGET) reported larger GRVs with energy-dense (1.5kcal/ml) compared with standard (1.0kcal/ml) enteral nutrition (EN), warranting further exploration.

Objective: To assess the incidence, risk factors, duration and timing of large GRVs (≥250ml) and its relationship to clinical outcomes in mechanically ventilated adults.

Design: A post-hoc analysis of TARGET data in patients with at least one GRV recorded. Data are n (%) or median [IQR].

Results: Of 3876 included patients, 1777 (46%) had at least one GRV≥250ml, which was more common in males (50 vs 39%; P < 0.001) and in patients receiving energy-dense compared with standard EN (52 vs 40%; RR=1.27 (95% CI: 1.19, 1.36); P < 0.001) in whom it also lasted longer (1 [0-2] vs 0 [0-1] days; P < 0.001), with no difference in time of onset after EN initiation (Day 1 [0-2] vs 1 [0-2]; P = 0.970). Patients with GRV≥250ml were more likely to have the following: vasopressor administration (88 vs 76%; RR=1.15 (1.12, 1.19); P < 0.001), positive blood cultures (16 vs 8%; RR=1.92 (1.60, 2.31); P < 0.001), intravenous antimicrobials (88 vs 81%; RR=1.09 (1.06, 1.12); P < 0.001), and prolonged ICU stay (ICU-free days to day 28; 12.9 [0.0-21.0] vs 20.0 [3.9-24.0]; P < 0.001), hospital stay (hospital-free days to day 28: 0.0 [0.0-12.0] vs 7.0 [0.0-17.6] days; P < 0.001), ventilatory support (ventilator-free days to day 28: 16.0 [0.0-23.0] vs 22.0 [8.0-25.0]; P < 0.001) and a higher 90-day mortality (29 vs 23%; adjusted: RR=1.17 (1.05, 1.30); P = 0.003).

Conclusion: Large GRVs were more common in males and those receiving energy-dense formulae, occurred early and were short-lived, and were associated with a number of negative clinical sequelae, including increased mortality, even when adjusted for illness severity. Clinical trial registration number: NCT02306746. URL: https://clinicaltrials.gov/ct2/show/NCT02306746.

In this study, we evaluated the ability of negatively charged bio-degradable nanoparticles, ONP- 302, to inhibit tumor growth. Therapeutic treatment with ONP-302 in vivo resulted in a marked delay in tumor growth in three different syngeneic tumor models in immunocompetent mice. ONP- 302 efficacy persisted with depletion of CD8+ T cells in immunocompetent mice and also was effective in immune deficient mice. Examination of ONP-302 effects on components of the tumor microenvironment (TME) were explored. ONP-302 treatment caused a gene expression shift in TAMs toward the pro-inflammatory M1 type and substantially inhibited the expression of genes associated with the pro-tumorigenic function of CAFs. ONP-302 also induced apoptosis in CAFs in the TME. Together, these data support further development of ONP-302 as a novel first-in- class anti-cancer therapeutic that can be used as a single-agent as well as in combination therapies for the treatment of solid tumors due to its ability to modulate the TME.

Boron is an important element in nuclear reactor technology due to its high neutron absorption cross section of B isotope. Isotopic composition of B (IC, B/B atom ratio) determination in finished neutron absorbers is a necessity under chemical quality control (CQC). We report an innovative greener method for rapid and non-destructive approach of isotopic composition determination of B in "as received" boron based ceramic neutron absorbers including boron carbides and hexa-borides by external (in air) Particle Induced Gamma-ray Emission (PIGE) using 3.5 MeV proton beam. It involves irradiation of "as received" powder samples wrapped in a thin Mylar film and measurement of prompt gamma rays at 429, 718 and 2125 keV from B(p,αγ)Be, B(p,p'γ)B and B(p,p'γ)B, respectively, using a HPGe detector system. The method was standardized with natural and enriched BC powders. For validation, the results of isotopic composition obtained from "as received" samples were compared with that obtained from pellet samples using both external and vacuum chamber PIGE methods. IC values obtained for natural to B enriched samples (19.8-67 atom % of B) are very encouraging with 1-2% and 0.3-0.7% uncertainties from single and replicate sample experiments. The method is truly non-destructive as the samples can be returned back as such after the experiment as they are not radioactive. Compared to existing PIGE method for isotopic composition of B, the developed method keeps promise for wide applications as it is simple, sensitive and rapid and it does not require vacuum, pellet preparation with a binder, exact mass of the sample and beam current measurement.

The repose angle is a key geometric property that characterises the inter-particle friction and thereby granular flows. One of the common methods to measure this property is to deposit a pile by extracting a pre-filled cylinder and letting the material flow out. While the repose angle of spherical beads is insensitive to the aspect ratio of this pre-filled column, we find that long flexible granular chains show a remarkable transition from stable vertical columns to conical piles depending on the aspect ratio. Below a critical aspect ratio, the cessation of flow of granular chains due to inter-chain entanglement stabilises the columns, while above the critical aspect ratio the conical piles of long granular chains arise not out of shear flow but instead through a series of column collapse instabilities during the deposition process. We also identify the critical chain length below which the granular chains flow and behave similar to spherical particles.