Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-boundpaclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumabepaclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or 12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m 2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression 1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P ¼ 0.20; median PFS 6.0 months with atezolizumabepaclitaxel versus 5.7 months with placeboepaclitaxel]. In the PD-L1-positive population, atezolizumabepaclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placeboepaclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumabepaclitaxel versus 28.3 months with placeboe paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov: NCT03125902.

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In this review, we present the environmental perspectives of the viruses and antiviral drugs related to SARS-CoV-2. The present review paper discusses occurrence, fate, transport, susceptibility, and inactivation mechanisms of viruses in the environment as well as environmental occurrence and fate of antiviral drugs, and prospects (prevalence and occurrence) of antiviral drug resistance (both antiviral drug resistant viruses and antiviral resistance in the human). During winter, the number of viral disease cases and environmental occurrence of antiviral drug surge due to various biotic and abiotic factors such as transmission pathways, human behaviour, susceptibility, and immunity as well as cold climatic conditions. Adsorption and persistence critically determine the fate and transport of viruses in the environment. Inactivation and disinfection of virus include UV, alcohol, chemical-base methods but the susceptibility of virus against these methods varies. Wastewater treatment plants (WWTPs) are major sources of antiviral drugs and their metabolites and transformation products. Ecotoxicity of antiviral drug residues against aquatic organisms have been reported, however more threatening is the development of antiviral resistance, both in humans and in wild animal reservoirs. In particular, emergence of antiviral drug-resistant viruses via exposure of wild animals to high loads of antiviral residues during the current pandemic needs further evaluation.

(1996) solved the same problem with an adaptive grid technique. Carmo et al. (1993) applied the MacCormack finite-difference scheme to solve the two-dimensional Serre equations. They studied the propagation of a solitary wave, dam-break flow, and a solitary wave overpassing an island. Frazao (2002) used the Boussinesq equations to study the secondary, free-surface undulations due to opening of a sluice gate, which cannot be reproduced by numerical models based on hydrostatic pressure distribution. Walkley (1999) presented an extensive list of references on the Boussinesq approach. In most of the references cited above, steady Boussinesq equations are used to study rapidly varied flows in open channels and the first Boussinesq term is excluded. On the use of Boussinesq equations for studying DBF, a detailed quantitative approach is missing and no definite conclusions are drawn, e.g., the capabilities to simulate long amplitude waves, the contributions of individual Boussinesq terms, the effects of bed slope, and roughness characteristics on the evolution of the free surface. In this paper, Boussinesq equations are solved numerically to simulate DBF with nonhydrostatic pressure distribution. The governing equations are first presented. The numerical solution procedure, and the initial and boundary conditions are then discussed. This is followed by a presentation of the results and the conclusion of the investigations.

This work presents numerical computations for the analysis of Dam-Break Flow using two-dimensional flow equations in a vertical plane. The numerical model uses the general approach of the simplified marker and cell method combined with the volume of fluid approach for the surface tracking. The time evolution of flow depth at the dam site and the evolution of the pressure distribution are investigated for both wet and dry bed conditions. The effect of the initially nonhydrostatic state on the long term surface profile and wave velocity are studied. These long term effects are found to be marginal in the case of wet-bed conditions, but are significant in dry-bed conditions. The dry-bed tip velocity immediately after the dam break, computed numerically, compares well with analytical results published previously. The time taken to obtain a constant flow depth at the dam site increases with decreasing initial depth ratio. The numerical result for this time elapse for dry-bed conditions is close to the experimentally obtained value.

In the intial two decades of the twenty-first century, antibiotic (AB) resistance in human pathogens has emerged as a major challenge for water, sanitation, and public health. Considering these challenges, we critically reviewed AB-related studies with particular emphasis on their (i) patterns of consumption, (ii) pathway prevalences and environmental implications in ambient waters, and (iii) benefits and limitations of existing AB removal/purging techniques. We found that lifestyle, land use, urbanization, the ease of availability, and the tendency of the medical practitioners to recommend ABs are the key factors governing the AB use pathway and enrichment in the environment. In the developing world, the most prevalent group of ABs is quinolone, whereas in the developed world, older-generation AB groups are most prevalent. Further, enormous variability in the consumption of ABs around the globe is explicitly highlighted in this study. Ciprofloxacin has been reported in the highest concentration among all the ABs with 28–31 mg L−1 in the raw wastewater of the Indian subcontinent. We found that adsorption may be one of the most efficient AB removal techniques, and NaOH-activated carbon prepared from Macadamia nut shells is the most effective adsorbent identified to date. The literature showed that the Langmuir isotherm and pseudo-second-order kinetic model explain the AB adsorption mechanism most effectively. The future challenge lies in developing advanced protocols and markers to prioritize the strategy and simulate the ecotoxicities of the individual and a mixture of ABs.

Steady oscillatory flow in a branched piping system with partial blockages is studied by using the frequency response method. The peak pressure frequency diagrams at the downstream end are developed with the partial blockage at different locations in the system by using the transfer matrix method. A systematic procedure is presented to estimate the size and the location of a single partial blockage in the system. For more than one partial blockage, it is observed that there is a definite relationship between the frequency responses of the individual and combined partial blockages.

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