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Solomon, Joshua J.; Danoff, Sonye K.; Woodhead, Felix A.; Hurwitz, Shelley, Maurer, Rie, Glaspole, Ian, Dellaripa, Paul F.; Gooptu, Bibek, Vassallo, Robert, Cox, P. Gerard, Flaherty, Kevin R.; Adamali, Huzaifa I.; Gibbons, Michael A.; Troy, Lauren, Forrest, Ian A.; Lasky, Joseph A.; Spencer, Lisa G.; Golden, Jeffrey, Scholand, Mary Beth, Chaudhuri, Nazia, Perrella, Mark A.; Lynch, David A.; Chambers, Daniel C.; Kolb, Martin, Spino, Cathie, Raghu, Ganesh, Goldberg, Hilary J.; Rosas, Ivan O.; Haynes-Harp, Shana, Poli, Fernando, Vidya, Coimbatore Sree, Baron, Rebecca R.; Clouser, Timothy, Doyle, Tracy, Maeda, Anthony, Highland, Kristin B.; Albayda, Jemima F.; Collins, Sarah E.; Suresh, Karthik S.; Davis, John M.; Limper, Andrew H.; Amigues, Isabel, Eliopoulos, Kristina, Swigris, Jeffery J.; Humphries, Stephen, Huntwork, John C.; Glynn, Chris, Duncan, Steve R.; Danila, Maria I.; Glassberg, Marilyn K.; Oberstein, Elana M.; Belloli, Elizabeth A.; Briggs, Linda, Nagaraja, Vivek, Cholewa, Linda, DiFranco, Donna, Green, Edward, Liffick, Christie, Naik, Tanvi, Montas, Genevieve, Lebiedz-Odrobina, Dorota, Bissell, Reba, Wener, Mark, Lancaster, Lisa H.; Crawford, Leslie J.; Chan, Karmela, Kaner, Robert J.; Morris, Alicia, Wu, Xiaoping, Khalidi, Nader A.; Ryerson, Christopher J.; Wong, Alyson W.; Fell, Charlene D.; LeClercq, Sharon A.; Hyman, Mark, Shapera, Shane, Mittoo, Shikha, Shaffu, Shireen, Gaffney, Karl, Wilson, Andrew M.; Barratt, Shaney, Gunawardena, Harsha, Hoyles, Rachel K.; David, Joel, Kewalramani, Namrata, Maher, Toby M.; Molyneaux, Philip L.; Kokosi, Maria A.; Cates, Matthew J.; Mandizha, Mandizha, Ashish, Abdul, Chelliah, Gladstone, Parfrey, Helen, Thillai, Muhunthan, Vila, Josephine, Fletcher, Sophie V.; Beirne, Paul, Favager, Clair, Brown, Jo, Dawson, Julie K.; Ortega, Pilar Rivera, Haque, Sahena, Watson, Pippa, Khoo, Jun K.; Symons, Karen, Youssef, Peter, Mackintosh, John A..
The Lancet Respiratory Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-2008216

ABSTRACT

Summary Background Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada). Adults aged 18–85 years were eligible for inclusion if they met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis and had interstitial lung disease on a high-resolution CT scan imaging and, when available, lung biopsy. Exclusion criteria include smoking, clinical history of other known causes of interstitial lung disease, and coexistant clinically significant COPD or asthma. Patients were randomly assigned (1:1) to receive 2403 mg oral pirfenidone (pirfenidone group) or placebo (placebo group) daily. The primary endpoint was the incidence of the composite endpoint of a decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or more or death during the 52-week treatment period assessed in the intention-to-treat population. Key secondary endpoints included change in absolute and FVC% over 52 weeks, the proportion of patients with a decline in FVC% of 10% or more, and the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02808871. Findings From May 15, 2017, to March 31, 2020, 231 patients were assessed for inclusion, of whom 123 patients were randomly assigned (63 [51%] to the pirfenidone group and 60 [49%] to the placebo group). The trial was stopped early (March 31, 2020) due to slow recruitment and the COVID-19 pandemic. The difference in the proportion of patients who met the composite primary endpoint (decline in FVC% from baseline of 10% or more or death) between the two groups was not significant (seven [11%] of 63 patients in the pirfenidone group vs nine [15%] of 60 patients in the placebo group;OR 0·67 [95% CI 0·22 to 2·03];p=0·48). Compared with the placebo group, patients in the pirfenidone group had a slower rate of decline in lung function, measured by estimated annual change in absolute FVC (–66 vs –146;p=0·0082) and FVC% (–1·02 vs –3·21;p=0·0028). The groups were similar with regards to the decline in FVC% by 10% or more (five [8%] participants in the pirfenidone group vs seven [12%] in the placebo group;OR 0·52 [95% CI 0·14–1·90];p=0·32) and the frequency of progression as defined by OMERACT (16 [25%] in the pirfenidone group vs 19 [32%] in the placebo group;OR 0·68 [0·30–1·54];p=0·35). There was no significant difference in the rate of treatment-emergent serious adverse events between the two groups, and there were no treatment-related deaths. Interpretation Due to early termination of the study and underpowering, the results should be interpreted with caution. Despite not meeting the composite primary endpoint, pirfenidone slowed the rate of decline of FVC over time in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials. Funding Genentech.

2.
Theory and Practice in Language Studies ; 12(7):1428-1434, 2022.
Article in English | ProQuest Central | ID: covidwho-1924780

ABSTRACT

-The depletion and drying of river water across India is a growing problem in the contemporary period. The ecologists have raised a huge concern regarding the depletion of river water in India. The drying, depletion, and disappearance of the rivers in India can be traced back to the Indus Valley Civilization. The ecological disturbance on land resulted in the loss of the Saraswati River. Amish Tripathi is a renowned figure in the realm of popular Indian mythological fiction. He has not only re-narrated the mythology of India but has also retold the history and geological reasons for the disappearance of the Saraswati River in his novel The Oath of Vayuputras (2013). The research article views the novel from a deep eco-critical perspective to examine the rationale behind the drying and depletion of the Saraswati River due to the destructive production and disposal of Somras and its toxic waste in the river. The article aims at showing the ecological disturbance in the biosphere which is the result of the progress of the human race towards civilization. The shunning of the eco-centric attitude and the development of a capitalistic attitude in humans towards other living beings have resulted in this disrupted eco-system in the present biosphere.

3.
Natural Volatiles & Essential Oils ; 8(4):8250-8265, 2021.
Article in English | CAB Abstracts | ID: covidwho-1864138

ABSTRACT

Today in India the greater part of the Government's administrations are made accessible electronically by worked on online framework and by expanding Internet network or making the nation carefully enabled in the field of innovation. Online frameworks where the info information enter the PC straightforwardly from the starting place (typically a terminal or workstation) or potentially in which yield information are communicated straightforwardly to that terminal starting place. In prior towards within into web based financial framework, we should know slight about the Indian financial framework. The financial area advancement can be partitioned into three stages Phase I: The Early Phase which lasted from 1770 to 1969, Phase II: The Nationalization Phase which lasted from 1969 to 1991 and Phase III: The Liberalization or the Banking Sector Reforms Phase which began in 1991 and continues to flourish till date. Fundamentally the banks are grouped into ordered into four classes that are Commercial banks, Small money banks, Payment banks and Co-employable banks. Today the customary financial framework in India is currently changing and moving towards the web based financial frameworks (modernization). In this view, this paper accentuation on consumer loyalty on internet banking during Covid-19, this investigation was led in Chengalpattu locale. Tests of 50 respondents were chosen to this investigation and the information's gathered through Google structures review techniques on working experts and understudies. The gathered information has been dissected through SPSS and the discoveries are shows that the exchange of internet banking is more advantageous than branch banking. Lastly this investigation may additionally leads with enormous example size on different areas.

5.
11th International Advanced Computing Conference, IACC 2021 ; 1528 CCIS:3-10, 2022.
Article in English | Scopus | ID: covidwho-1718571

ABSTRACT

Spread of “COVID” has taken over life of several people all around the world. In initial stages, it was gradually affecting the humans and as days goes on it started to drastically affect several people. This is because it spreads from one person to others easily. In this pandemic situation, in order to manage this pandemic situation, we must know the rate at which the infection gets spread and the analysis can be done with the pervious confirmed and death cases with the help of data sets available in web resources. ARIMA (Auto Regressive Integrated Moving Average) model can be used in forecasting the spread of COVID with the previous data sets extracted from Kaggle. Here have considered the data from March 2020 to June 2021 and predicted the COVID cases for the next one month July 2021. In specific, it has concentrated towards one particular state Tamilnadu from INDIA. © 2022, Springer Nature Switzerland AG.

7.
Smruthi Karthikeyan; Joshua I Levy; Peter De Hoff; Greg Humphrey; Amanda Birmingham; Kristen Jepsen; Sawyer Farmer; Helena M. Tubb; Tommy Valles; Caitlin E Tribelhorn; Rebecca Tsai; Stefan Aigner; Shashank Sathe; Niema Moshiri; Benjamin Henson; Abbas Hakim; Nathan A Baer; Tom Barber; Pedro Belda-Ferre; Marisol Chacon; Willi Cheung; Evelyn S Crescini; Emily R Eisner; Alma L Lastrella; Elijah S Lawrence; Clarisse A Marotz; Toan T Ngo; Tyler Ostrander; Ashley Plascencia; Rodolfo A Salido; Phoebe Seaver; Elizabeth W Smoot; Daniel McDonald; Robert M Neuhard; Angela L Scioscia; Alysson M. Satterlund; Elizabeth H Simmons; Dismas B. Abelman; David Brenner; Judith Carbone Bruner; Anne Buckley; Michael Ellison; Jeffrey Gattas; Steven L Gonias; Matt Hale; Faith Kirkham Hawkins; Lydia Ikeda; Hemlata Jhaveri; Ted Johnson; Vince Kellen; Brendan Kremer; Gary C. Matthews; Ronald McLawhon; Pierre Ouillet; Daniel Park; Allorah Pradenas; Sharon Reed; Lindsay Riggs; Alison M. Sanders; Bradley Sollenberger; Angela Song; Benjamin White; Terri Winbush; Christine M Aceves; Catelyn Anderson; Karthik Gangavarapu; Emory Hufbauer; Ezra Kurzban; Justin Lee; Nathaniel L Matteson; Edyth Parker; Sarah A Perkins; Karthik S Ramesh; Refugio Robles-Sikisaka; Madison A Schwab; Emily Spencer; Shirlee Wohl; Laura Nicholson; Ian H Mchardy; David P Dimmock; Charlotte A Hobbs; Omid Bakhtar; Aaron Harding; Art Mendoza; Alexandre Bolze; David Becker; Elizabeth T Cirulli; Magnus Isaksson; Kelly M Schiabor Barrett; Nicole L Washington; John D Malone; Ashleigh Murphy Schafer; Nikos Gurfield; Sarah Stous; Rebecca Fielding-Miller; Tommi Gaines; Richard Garfein; Cheryl A. M. Anderson; Natasha K. Martin; Robert T Schooley; Brett Austin; Duncan R. MacCannell; Stephen F Kingsmore; William Lee; Seema Shah; Eric McDonald; Alexander T. Yu; Mark Zeller; Kathleen M Fisch; Christopher A. Longhurst; Patty Maysent; David Pride; Pradeep K. Khosla; Louise C Laurent; Gene W Yeo; Kristian G Andersen; Rob Knight.
Preprint in English | medRxiv | ID: ppmedrxiv-21268143

ABSTRACT

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

8.
Preprint in English | bioRxiv | ID: ppbiorxiv-410357

ABSTRACT

Viruses, being obligate intracellular parasites, must first attach themselves and gain entry into host cells. Viral fusion machinery is the central player in the viral attachment process in almost every viral disease. Viruses have incorporated an array of efficient fusion proteins on their surfaces to bind efficiently to host cell receptors. They make use of the host proteolytic enzymes to rearrange their surface protein(s) into the form which facilitates their binding to host-cell membrane proteins and subsequently, fusion. This stage of viral entry is very critical and has many therapeutic implications. The current global pandemic of COVID-19 has sparked severe health crisis and economic shutdowns. SARS-CoV2, the etiological agent of the disease has led to millions of deaths and brought the scientific community together in an attempt to understand the mechanisms of SARS-CoV2 pathogenesis and mortality. Like other viral fusion machinery, CoV2 spike (S) glycoprotein- The Demogorgon poses the same questions about viral-host cell fusion. The intermediate stages of S protein-mediated viral fusion are unclear owing to the lack of structural insights and concrete biochemical evidence. The mechanism of conformational transition is still unclear. S protein binding and fusion with host cell receptors, Eg., angiotensin-converting enzyme-2 (ACE2) is accompanied by cleavage of S1/S2 subunits. To track the key events of viral-host cell fusion, we have identified (in silico) that low pH-induced conformational change and ACE-2 binding events promote S1 dissociation. Deciphering key mechanistic insights of SARS-CoV2 fusion will further our understanding of other class-I fusion proteins

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