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The Axon Initial Segment: An Updated Viewpoint

Christophe Leterrier
Feb 28, 2018; 38:2135-2145
Viewpoints




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François Villeroy de Galhau: From the emergency crisis response to initial thinking on the post-crisis environment

Hearing of Mr François Villeroy de Galhau, Governor of the Bank of France, before the Section for the Economy and Finance of the French Economic, Social and Environmental Council, Paris, 8 April 2020.




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Aero Design Series – Stock Wheel – Part 1: Intro and Initial Mockup

In this case, we will be reproducing a wheel in SOLIDWORKS based on measurements of the actual part. This tutorial series will span the full design process, from initial mockup all the way to final details.

Author information

Matthew Gruber is an alumni of Concordia University's Aero Design and Design/Build/Fly teams in 2015 through 2017, having joined after gaining an interest in helicopters and airplanes from living in Alaska.

Now is in his 3rd year in the airframe stress group of the 525 helicopter program at Bell and with 1 year of internships at Bombardier behind him, he credits the hands-on learning and team project experiences in SAE and D/B/F as the most formative in his path towards aerospace engineering. Being able to create in programs like SolidWorks and then to build into realization is one of the most rewarding aspects of engineering.

In his spare time, Matt likes backcountry snowboarding with his family dogs, bicycling for commuting, mountain trails and touring, looking for music and hanging out with friends and family.

For fun, for practice, and for a connection with the education and University communities and you the students, Matt is stoked to bring you these aero design video series.

The post Aero Design Series – Stock Wheel – Part 1: Intro and Initial Mockup appeared first on SOLIDWORKS Education Blog.




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Chronic Thrombocytopenia as the Initial Manifestation of STIM1-Related Disorders

Pediatric thrombocytopenia has a wide differential diagnosis, and recently, genetic testing to identify its etiology has become more common. We present a case of a 16-year-old boy with a history of chronic moderate thrombocytopenia, who later developed constitutional symptoms and bilateral hand edema with cold exposure. Laboratory evaluation revealed evidence both of inflammation and elevated muscle enzymes. These abnormalities persisted over months. His thrombocytopenia was determined to be immune mediated. Imaging revealed lymphadenopathy and asplenia, and a muscle biopsy was consistent with tubular aggregate myopathy. Ophthalmology evaluation noted photosensitivity, pupillary miosis, and iris hypoplasia. Genetic testing demonstrated a pathogenic variant in STIM1 consistent with autosomal dominant Stormorken syndrome. Our case is novel because of the overlap of phenotypes ascribed to both gain-of-function and loss-of-function pathogenic variants in STIM1, thereby blurring the distinctions between these previously described syndromes. Pediatricians should consider checking muscle enzymes when patients present with thrombocytopenia and arthralgia, myalgia, and/or muscle weakness. Our case highlights the importance of both multidisciplinary care and genetic testing in cases of chronic unexplained thrombocytopenia. By understanding the underlying genetic mechanism to a patient’s thrombocytopenia, providers are better equipped to make more precise medical management recommendations.




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Use of and Regional Variation in Initial CT Imaging for Kidney Stones

Professional organizations recommend ultrasound as the initial diagnostic imaging modality for children with suspected nephrolithiasis. Computed tomography utilization for children with nephrolithiasis treated at freestanding children’s hospitals is common and varies substantially by hospital.

The high prevalence and regional variability of CT as the first imaging study for children with nephrolithiasis who presented to emergency departments, outpatient clinics, and hospitals throughout the United States indicate that current imaging practices deviate substantially from guidelines. (Read the full article)




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Timing of Initial Well-Child Visit and Readmissions of Newborns

Current recommendations for the first outpatient visit for newborns are based on known health risks during the first week of life. Knowledge of the relationship between early well child visits and hospital readmissions may inform newborn health policy interventions.

Newborns who have a first well child visit within the recommended time period after hospital discharge are substantially less likely be readmitted. Obstacles to early follow-up should be addressed to reduce the risk of readmission in this population. (Read the full article)




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COVID-19 in Children: Initial Characterization of the Pediatric Disease

Andrea T. Cruz
Apr 8, 2020; 0:peds.2020-0834v2-e20200834
COMMENTARY




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Oral Versus Initial Intravenous Therapy for Urinary Tract Infections in Young Febrile Children

Alejandro Hoberman
Jul 1, 1999; 104:79-86
ARTICLES




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Prolonged Duration of Initial Empirical Antibiotic Treatment Is Associated With Increased Rates of Necrotizing Enterocolitis and Death for Extremely Low Birth Weight Infants

C. Michael Cotten
Jan 1, 2009; 123:58-66
ARTICLES




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Initial shortlist announced for 2012/13 UEFA Best Player in Europe Award

040 - Inaugural Best Women’s Player in Europe Award launched




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COVID-19 in Children: Initial Characterization of the Pediatric Disease





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KVM kvm_inject_page_fault Uninitialized Memory Leak

KVM suffers from an uninitialized memory leak vulnerability in kvm_inject_page_fault.




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Quest InTrust Annotation Objects Uninitialized Pointer

This Metasploit module exploits an uninitialized variable vulnerability in the Annotation Objects ActiveX component. The activeX component loads into memory without opting into ALSR so this module exploits the vulnerability against windows Vista and Windows 7 targets. A large heap spray is required to fulfill the requirement that EAX points to part of the ROP chain in a heap chunk and the calculated call will hit the pivot in a separate heap chunk. This will take some time in the users browser.




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Why Kingsoft Cloud's Initial Reports Are Promising




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Rail regulation: ORR concludes its initial consultation on the 2018 Periodic Review of Network Rail

Background - The 2018 Periodic Review The Office of Rail and Road (“ORR”) has recently published its conclusions (the “Conclusions”) following its initial consultation in relation to the creation of the 2018 Periodic Review ...




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Coronavirus - Deferral of initial margin requirements for derivatives announced – Global

On 3 April 2020, the Basel Committee on Banking Supervision (“BCBS”) and the International Organization of Securities Commissions (“IOSCO”) issued a statement recommending an extension to Phases 5 and 6 of the initial margin ...




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Initial AFRICOM Civilian Casualty Assessment Quarterly Report

[Africom] As part of the command's commitment to transparency, U.S. Africa Command is implementing a quarterly report on the status of ongoing and completed civilian casualty allegations and assessments. This initiative was directed by U.S. Army Gen. Stephen Townsend, commander, U.S. Africa Command, to increase transparency regarding civilian casualty allegations that are reported to the command while demonstrating the U.S. military's constant commitment to minimizing collateral damage in the pursuit of




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Ayushmann Khurrana recalls manipulative offers made by directors during his initial days

Ayushmann Khurrana is riding high in his career right now but the road to success was no bed of roses for him




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Tabloid wins initial court battle against UK royal Meghan

London's High Court on Friday threw out part of a claim brought by Meghan, Britain's Duchess of Sussex, against a tabloid newspaper for breaching her privacy, ruling that it had not acted dishonestly. Lauren Anthony reports.




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Initial Resuscitation Algorithm for Children




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Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine [Neuroscience]

The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological...




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Theophylline Acetaldehyde as the Initial Product in Doxophylline Metabolism in Human Liver [Articles]

Doxophylline (DOXO) and theophylline are widely used as bronchodilators for treating asthma and chronic obstructive pulmonary disease, and DOXO has a better safety profile than theophylline. How DOXO’s metabolism and disposition affect its antiasthmatic efficacy and safety remains to be explored. In this study, the metabolites of DOXO were characterized. A total of nine metabolites of DOXO were identified in vitro using liver microsomes from human and four other animal species. Among them, six metabolites were reported for the first time. The top three metabolites were theophylline acetaldehyde (M1), theophylline-7-acetic acid (M2), and etophylline (M4). A comparative analysis of DOXO metabolism in human using liver microsomes, S9 fraction, and plasma samples demonstrated the following: 1) The metabolism of DOXO began with a cytochrome P450 (P450)–mediated, rate-limiting step at the C ring and produced M1, the most abundant metabolite in human liver microsomes. However, in human plasma, the M1 production was rather low. 2) M1 was further converted to M2 and M4, the end products of DOXO metabolism in vivo, by non-P450 dismutase in the cytosol. This dismutation process also relied on the ratio of NADP+/NADPH in the cell. These findings for the first time elucidated the metabolic sites and routes of DOXO metabolism in human.

SIGNIFICANCE STATEMENT

We systematically characterized doxophylline metabolism using in vitro and in vivo assays. Our findings evolved the understandings of metabolic sites and pathways for methylxanthine derivatives with the aldehyde functional group.




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The progressive development of microfabrics from initial deposition to slump deformation: an example from a modern sedimenary melange on the Nankai Prism

The progressive development of microfabrics from initial deposition to slump deformation and then a submarine slide was investigated in an active subduction zone using cores recovered during the Integrated Ocean Drilling Program Expedition 333. A Pleistocene–Holocene sequence was recovered at Site C0018A, which was located on a slope basin on the footwall of the megasplay fault in the Nankai Trough, SW Japan. Six mass-transport deposit units intercalated with coherent intervals were recovered from the upper 190 m of the drilled succession. The initial microfabrics in the undeformed hemipelagic sediments were characterized by random and porous fabrics composed predominantly of clay aggregations and connectors. The initial fabrics were cardhouse fabrics, which consist of clay flakes with edge-to-edge (E–E) and/or edge-to-face (E–F) contacts. These initial microfabrics developed into compacted microfabrics, which are random and consolidated fabrics (bookhouse fabrics) that consist of clay flakes with E–F and/or face-to-face (F–F) contacts and develop during burial as a pure shear deformation. During slumping, these fabrics were then deformed under simple shear to become predominantly F–F contacts and form clay chains. Thus, the microfabrics in these submarine slides are a sedimentary mélange that developed locally into a preferred clay orientation with F–F contacts.

Supplementary material: A schematic illustration showing sedimentation processes and fabrics is available at https://doi.org/10.6084/m9.figshare.c.4483385

Thematic collection: This article is part of the Polygenetic mélanges collection available at: https://www.lyellcollection.org/cc/polygenetic-melanges




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Initial Glycemic Control and Care Among Younger Adults Diagnosed With Type 2 Diabetes

OBJECTIVE

The prevalence of type 2 diabetes is increasing among adults under age 45. Onset of type 2 diabetes at a younger age increases an individual’s risk for diabetes-related complications. Given the lasting benefits conferred by early glycemic control, we compared glycemic control and initial care between adults with younger onset (21–44 years) and mid-age onset (45–64 years) of type 2 diabetes.

RESEARCH DESIGN AND METHODS

Using data from a large, integrated health care system, we identified 32,137 adults (aged 21–64 years) with incident diabetes (first HbA1c ≥6.5% [≥48 mmol/mol]). We excluded anyone with evidence of prior type 2 diabetes, gestational diabetes mellitus, or type 1 diabetes. We used generalized linear mixed models, adjusting for demographic and clinical variables, to examine differences in glycemic control and care at 1 year.

RESULTS

Of identified individuals, 26.4% had younger-onset and 73.6% had mid-age–onset type 2 diabetes. Adults with younger onset had higher initial mean HbA1c values (8.9% [74 mmol/mol]) than adults with onset in mid-age (8.4% [68 mmol/mol]) (P < 0.0001) and lower odds of achieving an HbA1c <7% (<53 mmol/mol) 1 year after the diagnosis (adjusted odds ratio [aOR] 0.70 [95% CI 0.66–0.74]), even after accounting for HbA1c at diagnosis. Adults with younger onset had lower odds of in-person primary care contact (aOR 0.82 [95% CI 0.76–0.89]) than those with onset during mid-age, but they did not differ in telephone contact (1.05 [0.99–1.10]). Adults with younger onset had higher odds of starting metformin (aOR 1.20 [95% CI 1.12–1.29]) but lower odds of adhering to that medication (0.74 [0.69–0.80]).

CONCLUSIONS

Adults with onset of type 2 diabetes at a younger age were less likely to achieve glycemic control at 1 year following diagnosis, suggesting the need for tailored care approaches to improve outcomes for this high-risk patient population.




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ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non-Small Cell Lung Cancer

Purpose:

Currently, an optimal therapeutic strategy comprising molecularly targeted agents for treating EGFR-mutated non–small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib is not available. Therefore, the initial therapeutic intervention is crucial for the prolonged survival of these patients. The activation of anexelekto (AXL) signaling is known to be associated with intrinsic and acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). In this study, we investigated the best therapeutic strategy to combat AXL-induced tolerance to EGFR-TKIs using the novel AXL inhibitor ONO-7475.

Experimental Design:

We examined the efficacy of ONO-7475 in combination with EGFR-TKIs in EGFR-mutated NSCLC cells using in vitro and in vivo experiments. We investigated the correlation between AXL expression in tumors and clinical outcomes with osimertinib for EGFR-mutated NSCLC patients with acquired resistance to initial EGFR-TKIs.

Results:

ONO-7475 sensitized AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs osimertinib and dacomitinib. In addition, ONO-7475 suppressed the emergence and maintenance of EGFR-TKI–tolerant cells. In the cell line–derived xenograft models of AXL-overexpressing EGFR-mutated lung cancer treated with osimertinib, initial combination therapy of ONO-7475 and osimertinib markedly regressed tumors and delayed tumor regrowth compared with osimertinib alone or the combination after acquired resistance to osimertinib. AXL expression in EGFR-TKI refractory tumors did not correlate with the sensitivity of osimertinib.

Conclusions:

These results demonstrate that ONO-7475 suppresses the emergence and maintenance of tolerant cells to the initial EGFR-TKIs, osimertinib or dacomitinib, in AXL-overexpressing EGFR-mutated NSCLC cells, suggesting that ONO-7475 and osimertinib is a highly potent combination for initial treatment.




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Questions raised over coronavirus pandemic response with Boris Johnson&apos;s initial actions criticised

Questions have been raised over the Government's response to the coronavirus pandemic with Boris Johnson's early actions amid the crisis criticised.




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Better Call Saul: Vince Gilligan admits he initially didn&apos;t want to bring Breaking Bad&apos;s Lalo back

'Man, I was wrong'




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600,000 people out of a job, 1.6 million with no income from work: ABS estimates the initial cost of coronavirus

A new survey from the ABS shows the extreme effect of coronavirus social-distancing measures on employment, with well over a million workers losing their incomes in the space of a month.




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EU-led coronavirus fundraiser targets initial 7.5 billion euros

A pledging conference led by the European Union (EU) has set an initial target of 7.5 billion euros ($8.1…



  • Anti-virals/Antibiotics and Infectious diseases/Coronavirus/EIB Group/Europe/Focus On/Government Affairs/Health Medical Pharma/Pharmaceutical/Public health

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No benefit of initial invasive strategy for managing CAD in advanced CKD




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Clinical utility of the exosome based ExoDx Prostate(<i>IntelliScore</i>) EPI test in men presenting for initial Biopsy with a PSA 2–10 ng/mL




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USAA chief: Coronavirus 'cabin fever' may be behind car crash uptick after initial steep decline

"The last couple of weeks we've seen a slight uptick in those rates, certainly not because stores are reopening," USAA CEO Wayne Peacock told CNBC.




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SCOOP: Rajkumar Hirani's next with Shah Rukh Khan was initially a two-hero film; filmmaker had Salman in mind?

The two of the biggest superstars of Bollywood, Shah Rukh Khan and Salman Khan, also have an electrifying chemistry on screen. This was evident in Rakesh Roshan’s 1995 blockbuster Karan Arjun. Even in the romance saga Kuch Kuch Hota Hai, where Salman had a supporting part, the film went on another level whenever they came forward. Hum Tumhare Hain Sanam today is memorable chiefly because it starred both of them together. It’s been 18 years since they both came together, though they were sweet enough to do special appearances in each other’s films (Om Shanti Om, Tubelight and Zero). But to see them together in a two-hero flick is something that fans have been waiting for keenly. Their excitement did arise when reports emerged that Sanjay Leela Bhansali was planning to cast Shah Rukh Khan and Salman Khan in his next flick. But sadly, the project failed to take off.

After SRK’s Zero tanked, the star took a long time in deciding his next and finally, if reports are believed, he has given his nod to blockbuster filmmaker Rajkumar Hirani. However, as per a write-up by Rajeev Masand in Open magazine, Rajkumar Hirani had initially approached SRK with a different film. The article states that Rajkumar had the concept of a two-hero film in his mind. For this project, he wanted to cast both Shah Rukh Khan and Salman Khan. However, when he met SRK, he insisted that he’s keen on doing a solo-starrer. Hence, Rajkumar Hirani went back to the drawing board and he finally came up with an idea which was fine to both the filmmaker and the actor.

Rajkumar Hirani is writing the script with his regular colleague, Abhijat Joshi. As it is his style, Rajkumar Hirani is taking his own sweet time to write and fine-tune the script. He’s been sharing all the drafts with the superstar, who also provides his feedback and input to Rajkumar. However, an official announcement regarding this film will happen only when a fully satisfied Rajkumar Hirani locks the script. This is being done at the behest of the filmmaker and Shah Rukh Khan reportedly has no qualms in delaying the announcement.

Recently, SRK had got his fans excited when in a reply to a fan question on Twitter, he had hinted that his film with Rajkumar Hirani is indeed on.

 

Also Read: Rajkumar Hirani and Sri Sri Ravi Shankar to have an insightful conversation on the Heart To Heart Show




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Initial Coin Offerings (ICOs) for SME Financing

This report analyses the emergence and potential of ICOs as a financing mechanism for start-ups and small and medium-sized enterprises (SMEs), examines the benefits and challenges of this mechanism for small businesses and investors, and discusses policy implications of ICO activity for inclusive financing of SMEs and the real economy.




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EU-led coronavirus funding drive nears initial €7.5bn target

Pledging conference underscores urgency to develop vaccine and distribute it worldwide




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Initial finding backs US health official over virus sidelining

Rick Bright’s lawyers say federal investigators recommend he be reinstated during probe




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Smart Tips for Successfully Navigating the Initial Franchisor-Franchisee Interview

Once you have a few franchises in mind, you'll be talking to a franchise rep from each company. Here's the skinny on how that phone call should go.



  • Buying a Franchise

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Meghan wears necklace adorned with Prince Harry and Archie's initials in New York

Meghan Markle, 38, kept Prince Harry, 35, and four-month-old Archie close to her chest as she donned a delicate gold necklace with their initials on during her New York trip.




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Shakira's Whenever, Wherever hits top spot on iTunes chart NINETEEN YEARS after its initial release

The song reached number one on the iTunes Top 100 songs chart this week, a position it was never able to reach even in its heyday.




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Australian with COVID-19 initially thought it was 'no worse than a cold' before things changed

Bridget Wilkins, 29, was diagnosed with coronavirus in early March after flying from London to Brisbane , via Singapore , for a wedding.




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Kate Middleton pays tribute to her children by wearing necklace engraved with their initials

Kate Middleton, 38, paid a touching tribute to her children by wearing a £1,070 necklace by Daniella Draper as she arrived in Cardiff today. It was engraved with their initials 'G, L, C.'




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Blackburn Rovers complete the initial loan signing of Nottingham Forest striker Ben Brereton

Blackburn Rovers have completed the loan signing of Nottingham Forest striker Ben Brereton on an initial loan which can be made permanent on January 1, 2019.




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Charlie Sheen initially cast on Dancing With The Stars but walked away (and may have cost him gig)

The 54-year-old actor was initially set to compete on the current season 28 of Dancing With The Stars but walked away from the opportunity according to a Wednesday report from Us Weekly.




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Cardiff set to make improved offer for Wigan striker Kieffer Moore after initial bid was rejected

Cardiff City are expected to make an improved bid for Wigan Athletic striker Kieffer Moore. An offer of £2.3million was rejected last week but Moore was left out of Wigan's squad against Bristol City.




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Jack Wilshere reveals he initially didn't want to join the Gunners

Jack Wilshere spent 17 years at Arsenal, but the midfielder has revealed he was reluctant to join the club when he was offered a spot at just nine-years-old. 




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Vishal Aditya Singh On His Initial Struggle In The Industry: Did Not Have Money To Go For Auditions

TV actor Vishal Aditya Singh, who became a household name after his stint in Bigg Boss 13, opened about his initial struggle days and facing rejections.




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Facebook Stock Soars in Q1 Earnings After Initial Drop Amid Coronavirus Pandemic

The social networking giant also said it counts 2.99 billion monthly users across its family of apps, compared to 2.89 billion in the previous quarter.




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Tabloid wins initial court battle against UK royal Meghan

London's High Court on Friday threw out part of a claim brought by Meghan, Britain's Duchess of Sussex, against a tabloid newspaper for breaching her privacy, ruling that it had not acted dishonestly. Lauren Anthony reports.




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Initial Management of Acute Pancreatitis

This JAMA Clinical Guidelines Synopsis summarizes the American Gastroenterological Association Institute’s 2018 guideline on initial management of acute pancreatitis.