Spatio-temporal correspondence of aerosol optical depth between CMIP6 simulations and MODIS retrievals over India.

In the present work, the aerosol optical depth (AOD) at 550 nm of the moderate resolution imaging spectroradiometer (MODIS) onboard the Terra satellite was utilised to evaluate the AOD simulations of newly emerged general circulation models (GCMs) of coupled model intercomparison project-phase 6 (CMIP6) over the Indian landmass. Further, the AOD from the CMIP6 models has been compared with its previous generation models from CMIP5 to examine the extent of uncertainties in AOD with reference to the MODIS AOD datasets. The evolution of aerosols over India using the different shared socioeconomic pathways (SSPs) has also been studied till the year 2050. The results show that the CMIP5 and CMIP6 models underestimated the mean annual AOD of the Indian region as a whole. A multi-model mean (MMM) of thirteen GCMs from CMIP6 showed an underestimation of AOD by 40 to 60% over the Indo-Gangetic plains, while an overestimation of 60 to 80% in AOD was observed over the Peninsular and Central Indian regions in comparison with MODIS for the study period of 2001 to 2014. In future simulations, the pathway SSP370 has shown a significant increasing trend of AOD whereas SSP126 and SSP585 have shown significant decreasing trends of AOD by the year 2050. In the future, the changes in the AOD will mainly be contributed by the anthropogenic aerosols (AOA, BC, and Sulphates) emissions in all SSPs. The large bias of MMM with the MODIS requires further research in terms of analysing the accuracy of emission datasets that have been used to simulate the AODs by the CMIP6 models over the Indian region.

Data Driven Computational Design and Experimental Validation of Drugs for Accelerated Mitigation of Pandemic-like Scenarios.

Emerging pathogens are a historic threat to public health and economic stability. Current trial-and-error approaches to identify new therapeutics are often ineffective due to their inefficient exploration of the enormous small molecule design space. Here, we present a data-driven computational framework composed of hybrid evolutionary algorithms for evolving functional groups on existing drugs to improve their binding affinity toward the main protease (Mpro) of SARS-CoV-2. We show that combinations of functional groups and sites are critical to design drugs with improved binding affinity, which can be easily achieved using our framework by exploring a fraction of the available search space. Atomistic simulations and experimental validation elucidate that enhanced and prolonged interactions between functionalized drugs and Mpro residues result in their improved therapeutic value over that of the parental compound. Overall, this novel framework is extremely flexible and has the potential to rapidly design inhibitors for any protein with available crystal structures.

A review of recent advances and applications of machine learning in tribology.

In tribology, a considerable number of computational and experimental approaches to understand the interfacial characteristics of material surfaces in motion and tribological behaviors of materials have been considered to date. Despite being useful in providing important insights on the tribological properties of a system, at different length scales, a vast amount of data generated from these state-of-the-art techniques remains underutilized due to lack of analysis methods or limitations of existing analysis techniques. In principle, this data can be used to address intractable tribological problems including structure-property relationships in tribological systems and efficient lubricant design in a cost and time effective manner with the aid of machine learning. Specifically, data-driven machine learning methods have shown potential in unraveling complicated processes through the development of structure-property/functionality relationships based on the collected data. For example, neural networks are incredibly effective in modeling non-linear correlations and identifying primary hidden patterns associated with these phenomena. Here we present several exemplary studies that have demonstrated the proficiency of machine learning in understanding these critical factors. A successful implementation of neural networks, supervised, and stochastic learning approaches in identifying structure-property relationships have shed light on how machine learning may be used in certain tribological applications. Moreover, ranging from the design of lubricants, composites, and experimental processes to studying fretting wear and frictional mechanism, machine learning has been embraced either independently or integrated with optimization algorithms by scientists to study tribology. Accordingly, this review aims at providing a perspective on the recent advances in the applications of machine learning in tribology. The review on referenced simulation approaches and subsequent applications of machine learning in experimental and computational tribology shall motivate researchers to introduce the revolutionary approach of machine learning in efficiently studying tribology.

Safety, Immunogenicity, and Efficacy of a COVID-19 Vaccine (NVX-CoV2373) Co-administered With Seasonal Influenza Vaccines

BackgroundThe safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines has not yet been reported. MethodsA sub-study on influenza vaccine co-administration was conducted as part of the phase 3 randomized trial of the safety and efficacy of NVX-CoV2373. The first [~]400 participants meeting main study entry criteria and with no contraindications to influenza vaccination were invited to join the sub-study. After randomization in a 1:1 ratio to receive NVX-CoV2373 (n=217) or placebo (n=214), sub-study participants received an age-appropriate, licensed, open-label influenza vaccine with dose 1 of NVX-CoV2373. Reactogenicity was evaluated via electronic diary for 7 days post-vaccination in addition to monitoring for unsolicited adverse events (AEs), medically-attended AEs (MAAEs), and serious AEs (SAEs). Influenza haemagglutination inhibition and SARS-CoV-2 anti-spike IgG assays were performed. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed. Comparisons were made between sub-study and main study participants. FindingsSub-study participants were younger, more racially diverse, and had fewer comorbid conditions than main study participants. Reactogenicity events more common in the co-administration group included tenderness (70.1% vs 57.6%) or pain (39.7% vs 29.3%) at injection site, fatigue (27.7% vs 19.4%), and muscle pain (28.3% vs 21.4%). Rates of unsolicited AEs, MAAEs, and SAEs were low and balanced between the two groups. Co-administration resulted in no change to influenza vaccine immune response, while a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. Vaccine efficacy in the sub-study was 87.5% (95% CI: -0.2, 98.4) while efficacy in the main study was 89.8% (95% CI: 79.7, 95.5). InterpretationThis is the first study to demonstrate the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. The results suggest concomitant vaccination may be a viable immunisation strategy. FundingThis study was funded by Novavax, Inc. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for research articles published from December 2019 until 1 April 2021 with no language restrictions for the terms "SARS-CoV-2", "COVID-19", "vaccine", "co-administration", and "immunogenicity". There were no peer-reviewed publications describing the simultaneous use of any SARS-CoV-2 vaccine and another vaccine. Several vaccine manufacturers had recent publications on phase 3 trials results (Pfizer/BioNTech, Moderna, AstraZeneca, Janssen, and the Gamaleya Research Institute of Epidemiology and Microbiology). Neither these publications nor their clinical trials protocols (when publicly available) described co-administration and they often had trial criteria specifically excluding those with recent or planned vaccination with any licenced vaccine near or at the time of any study injection. Added value of this studyImmune interference and safety are always a concern when two vaccines are administered at the same time. This is the first study to demonstrate the safety and immunogenicity profile and clinical vaccine efficacy of a COVID-19 vaccine when co-administered with a seasonal influenza vaccine. Implications of all the available evidenceThis study provides much needed information to help guide national immunisation policy decision making on the critical issue of concomitant use of COVID-19 vaccines with influenza vaccines.

Effect of bilateral infraorbital nerve block on intraoperative anesthetic requirements, hemodynamics, glycemic levels, and extubation in infants undergoing cheiloplasty under general anesthesia

Background@#Inappropriate use of intravenous and inhaled anesthetics may be dangerous in infants undergoing facial cleft surgeries. This study primarily aimed to compare the effect of infraorbital nerve block on sevoflurane requirement in infants undergoing cheiloplasty. Intraoperative opioid consumption, hemodynamics, blood glucose levels, extubation time, and delirium were also compared. @*Methods@#This prospective, randomized, double-blinded study was conducted in 34 infants undergoing cheiloplasty under general anesthesia. After induction, group A received bilateral infraorbital nerve block with 0.5 mL of 0.5% bupivacaine and group B 0.5 mL saline. An increase in heart rate or blood pressure > 20% was managed by increasing sevoflurane by 2–2.5%, followed by fentanyl 0.5 µg/kg bolus. The chi-square test and independent-sample t-test were used where applicable. @*Results@#Demographics, duration of surgery, and intravenous fluids used were comparable between the groups.Compared to group A, patients in group B had significantly higher consumption of fentanyl (14.2 ± 4.4 µg vs. 22.1 ± 6.2 µg) and sevoflurane (14.2 ± 4.8 mL vs. 26.8 ± 15.6 mL). Intraoperative hemodynamic parameters were significantly lower in group A, the number of times increases in hemodynamic parameters occurred, and fentanyl supplemental bolus was required remained significantly lower in group A than in group B. Intraoperative glycemic levels remained higher in group B, and the extubation time was significantly shorter in group A than in group B (4.40 ± 1.60 min vs. 9.2 ± 2.18 min). Group A had a lesser occurrence of postoperative delirium. @*Conclusion@#Supplemental infraorbital block in infants undergoing cheiloplasty under general anesthesia resulted in significantly decreased anesthetic requirements and optimal hemodynamic and glycemic levels with faster extubation and lesser delirium.

Is routine chest radiography necessary after ultrasonography-guided catheter thoracostomy?

INTRODUCTION@#Many institutions still perform routine chest radiography (CXR) after tube thoracostomies despite current guidelines suggesting that this is not necessary for simple cases. We aimed to evaluate the usefulness of routine CXR following ultrasonography-guided catheter thoracostomies for the detection of complications of symptomatic pleural effusions in hospitalised patients.@*METHODS@#This was a retrospective review of 2,032 ultrasonography-guided thoracostomies on hospitalised patients with symptomatic effusions at a single institution from April 2012 to May 2015. The aetiology of effusions was not systemically registered, but patient demographics, procedural details and clinical outcomes were collected. Data was analysed using descriptive statistics and chi-square test. Generalised estimating equation analysis was performed to assess the relationship between CXR findings and complications while controlling for age.@*RESULTS@#Out of 2,032 CXRs, 92.96% (n = 1,889) were normal, 5.81% (n = 118) showed pneumothorax and 1.23% (n = 25) showed catheter kinking. 99 pneumothoraces and 24 kinked catheters were detected in the first hour post procedure. 97.40% (n = 115) of patients with pneumothorax were stable or had minor complications, such as a vasovagal event. 0.20% (n = 4) of the cases had a serious complication following chest drain insertion, resulting in cardiovascular collapse. There was no significant relationship between CXR results and occurrence of complications (p = 0.244). Amount of fluid drained or side of insertion did not affect the clinical outcome.@*CONCLUSION@#Routine use of CXR after tube thoracostomy did not significantly change patient management, which was concordant with recent guidelines. Instead, adverse clinical outcomes or procedural factors should guide investigations.

Projections of heat stress and associated work performance over India in response to global warming.

Summertime heat stress future projections from multi-model mean of 18 CMIP5 models show unprecedented increasing levels in the RCP 4.5 and RCP 8.5 emission scenarios over India. The estimated heat stress is found to have more impact on the coastal areas of India having exposure to more frequent days of extreme caution to danger category along with the increased probability of occurrence. The explicit amount of change in temperature, increase in the duration and intensity of warm days along with the modulation in large scale circulation in future are seemingly connected to the increasing levels of heat stress over India. A decline of 30 to 40% in the work performance is projected over India by the end of the century due to the elevated heat stress levels which pose great challenges to the country policy makers to design the safety mechanisms and to protect people working under continuous extreme hot weather conditions.

Intractable hepatic encephalopathy in cirrhotic patients: mid-term efficacy of balloon-occluded retrograde portosystemic shunt obliteration.

PURPOSE: To evaluate the efficacy and intermediate-term outcome of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hepatic encephalopathy (HE) secondary to portosystemic shunt (PSS) in cirrhotic patients. MATERIALS AND METHODS: Institutional review board (IRB) approval was obtained for this study and hospital records of patients who underwent BRTO, from August 2011 to August 2015, were analyzed. Based on the inclusion and exclusion criteria, 39 patients (age, 54.07 ± 9.1 years (37-67 years); 33 males and 6 females) with cirrhosis and spontaneous PSS were included. Clinical and laboratory parameters and HE grade were evaluated in all patients before and after the procedure. RESULTS: Forty sessions of BRTO were attempted in 39 patients. Follow-up imaging revealed complete obliteration of the treated PSS in all patients with clinical success in 37 patients (94.9%). The 1-, 2-, 3-, 4-, 5-, 6-, and 7-year HE-free survival rates among responders were 91.7%, 91.7%, 88.8%, 85.5%, 80.8%, 80.8%, and 80.8% respectively and overall survival rates were 89.7%, 82.1%, 76.9%, 74.4%, 74.4%, 64.8%, and 64.8% respectively. Logistic regression highlighted Child-Turcotte-Pugh (CTP) score at 6 months as a positive predictive factor of HE recurrence with a cutoff of ≥ 9. Five patients (12.8%) had fever and leukocytosis and 1 (2.6%) patient developed spontaneous bacterial peritonitis after the procedure. CONCLUSION: BRTO is an effective treatment for refractory HE in cirrhotics secondary to large PSS with a few possible complications. KEY POINTS: • BRTO is an effective and safe treatment for refractory HE, arising from PSS in cirrhotic patients. • Patients with preserved liver function show better outcome and CTP score is the most important predictor of relapse during follow-up.

An empirical method for source apportionment of black carbon aerosol: Results from Aethalometer observations at five different locations in India.

Black carbon (BC) aerosol emitted in incomplete combustion processes is known for causing warming in the climate system also poses serious health issues. Identification of the sources of BC is essential for the development of mitigation strategies to regulate their effects in changing climate. Among different observational and analytical techniques currently available, source apportionment methods based on optical measurements are relatively simple. For example, 'Aethalometer model' was developed based on Aethalometer observations. However, there are a few limitations with this model arising from assumption of wavelength and angstrom exponent pairs. We have developed an empirical method which also relies on Aethalometer observations named as 'Two alpha method' which assumes angstrom exponent from fossil fuel as 1 and estimates bio-mass fraction and angstrom exponent for bio-mass burning. This method has been applied to Aethalometer observations from five different locations (rural, semi-urban and urban) over Indian sub-continent to quantify sources of BC. Fossil fuel is found to be the major source of BC (∼70%) irrespective of the location. Collocated measurements of Carbon Monoxide (CO) over rural site correlated well with derived bio-mass fraction. Results from this study demonstrated the capabilities of empirical method and shall provide spatio-temporal variability in sources of BC if applied to more locations.

Genome to Phenome: Improving Animal Health, Production, and Well-Being - A New USDA Blueprint for Animal Genome Research 2018-2027.

In 2008, a consortium led by the Agricultural Research Service (ARS) and the National Institute for Food and Agriculture (NIFA) published the "Blueprint for USDA Efforts in Agricultural Animal Genomics 2008-2017," which served as a guiding document for research and funding in animal genomics. In the decade that followed, many of the goals set forth in the blueprint were accomplished. However, several other goals require further research. In addition, new topics not covered in the original blueprint, which are the result of emerging technologies, require exploration. To develop a new, updated blueprint, ARS and NIFA, along with scientists in the animal genomics field, convened a workshop titled "Genome to Phenome: A USDA Blueprint for Improving Animal Production" in November 2017, and these discussions were used to develop new goals for the next decade. Like the previous blueprint, these goals are grouped into the broad categories "Science to Practice," "Discovery Science," and "Infrastructure." New goals for characterizing the microbiome, enhancing the use of gene editing and other biotechnologies, and preserving genetic diversity are included in the new blueprint, along with updated goals within many genome research topics described in the previous blueprint. The updated blueprint that follows describes the vision, current state of the art, the research needed to advance the field, expected deliverables, and partnerships needed for each animal genomics research topic. Accomplishment of the goals described in the blueprint will significantly increase the ability to meet the demands for animal products by an increasing world population within the next decade.

Concomitant pseudopolymorphs of 10-deacetyl baccatin III.

Three new solvates [mono-dimethyl sulfoxide (mono-DMSO), mono-dimethyl acetamide (mono-DMA) and mono-dimethyl formamide (mono-DMF)] of 10-Deacetyl baccatin III, were generated by slow evaporation in DMSO, DMF, and DMSO/DMA (1:1) solvent systems respectively. Two concomitant forms mono-DMSO(a new form) and di-DMSO (a known form) were obtained in the DMSO solvent system. Yet two other concomitant forms mono-DMA (a new form) and di-DMSO (a known form) were obtained in DMSO/DMA (1:1) solvent system. A fourth solvate mono-DMF (a new form) was crystallized in unimolar ratio using DMF as a solvent. These solvates were characterized using powder X-ray diffraction, differential scanning calorimeter, thermogravimetric analysis (TGA), and spectroscopic [(13)C solid-state nuclear magnetic spectroscopy, solution (1)H NMR, and Fourier transform infrared] techniques. The interactions between host and guest molecules were elucitated by single-crystal X-ray diffraction data. In all the cases, guest molecules are connected to the host molecules by O-H∙∙∙O hydrogen bonds. A remarkable difference in the desolvation onset temperatures of di- and mono-DMSO solvates was observed which was also featured by a corresponding weight loss during TGA analysis.

Vapor-induced phase transformations in docetaxel.

Vapor-induced transformations of docetaxel anhydrous (form D(A)) under ambient conditions have been studied using methanol, ethanol, and water as the solvent media. The online vapor-induced transformations were monitored by powder X-ray diffractometry. New solid forms (solvates/hydrates/anhydrous) of docetaxel anhydrous were obtained in stoichiometric ratios which were characterized completely using powder X-ray diffraction, differential scanning calorimeter, thermogravimetric analysis, and spectroscopic ((13)C solid-state nuclear magnetic spectroscopy, solution (1)H NMR, and Fourier transform infrared) techniques. The new forms namely methanol solvate (D(M)), ethanol solvate (D(E)), monohydrate (D(MH)), trihydrate (D(TH)), and anhydrous (D(AN-I) and D(AN-II)) were identified through structural analysis.

Identification, synthesis, isolation and spectral characterization of potential impurities of montelukast sodium.

During the process development of montelukast sodium, three polar impurities and one non-polar impurity with respect to montelukast sodium were detected by simple reverse phase high-performance liquid chromatography (HPLC). Initially, all the four impurities were identified by the liquid chromatography-mass spectrometry (LC-MS) data and out of four impurities, three have been prepared by the synthetic method and remaining one is isolated by preparative HPLC. Based on the spectral data (IR, (1)H NMR, (13)C NMR and MS), the structure of these impurities 1-4 were characterised as 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropane acetamide (impurity-1), {1-[1-{3-[2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-3-(2-isopropenyl-phenyl)-propylsulfanylmethyl]-cyclopropyl}-acetic acid (impurity-2), 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (impurity-3) and 1-[[[(1R)-1-[3-[(1E)-2-(2-quinolinyl)ethenyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (impurity-4).

Pd-mediated synthesis of substituted benzenes fused with carbocycle/heterocycle.

A new Pd-catalyzed one-pot multicomponent coupling reaction for the construction of benzene ring fused with carbocycle or heterocycle under a Cu-free condition is described.