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After tasting success with his latest action packed film Rowdy Rathore, Bollywood star Akshay Kumar is back to his clean-shaven, gentlemanly image and says he does not like to be associated with the word ‘rowdy’ in real life.”Real life is different than reel life. In real life I am no longer a puppet as I am in reel life. I am a thoroughly different person in real life. Kicks and punches are the reel life stuff. I wonder why the word ‘rowdy’ is being used for me,” said Akshay, who was in the capital last night to attend Aaj Tak Care awards.Dressed in a chequered white shirt and a format suit, the 44-year-old said he was happy to see his film do well at the box office.Akshay, who is also known as the Khiladi of Bollywood for his action roles in the 90’s said that though his initial years in the industry were very tough, he is happy to have come so far.”My initial years in Bollywood was very tough. I had to struggle a lot. I always believed God was with me. I never deviated but rather focused on my efforts,” he said.Though the actor did not divulge much about his upcoming films, he said that his forthcoming film Khiladi 786 is an exciting project and he is glad to be part of it.”I believe Khiladi 786 is one of the important assignments of my life,” he said.When asked if he would like to enter the field of politics ever, Akshay said, “If I become a politician, I would definitely do something for sports.”advertisement
Defending champion Roger Federer won his seventh Dubai Championships title and second of the year in defeating top-ranked Novak Djokovic 6-3, 7-5 on Saturday.This marked the seventh consecutive year – 11th time in 13 years – that Federer or Djokovic won this title. The only other tournaments Federer won seven times are Wimbledon, and Halle, Germany, both on grass.”Ever since I won here the first time, I fell in love with the tournament,” Federer said. “The seventh is quite unbelievable. It sounds pretty crazy to me.”Federer, who has 84 career titles, won in Brisbane, Australia, in January.”He deserved it,” Djokovic said. “I expected that from him.”I knew he was going to chip and charge, come to the net, serve and volley.”The 5,000-seat stadium was sold out, but many more people were standing around at the top. They were treated to a high-caliber match. Federer needed five more aces to become just the fourth player since 1991 to serve 9,000 career aces. He served 12 in the final.He joined Goran Ivanisevic (10,183), Ivo Karlovic (9,375), and Andy Roddick (9,074) in cracking the 9,000 aces mark.”I even remember which one it was because I was counting them,” Federer said. “It was one of the swinger wides.”It’s nice to get past that so I don’t have to think about it ever again, or until the next thousand or so.”Federer saved all seven break points he faced, while Djokovic lost both break points he faced. Djokovic sailed a backhand long on break point in the eighth game of the first set.advertisementIn the second set, Djokovic had a 40-0 lead in the 11th game, but watched Federer rebound to break his serve with an inside out forehand crosscourt winner.”The first set belonged to me, but the second set belonged to him more, really,” Federer said. “It was a huge game at 5-all, 40-love for him.”I crawled my way back into that game and ended up breaking him,” Federer added. “That was big but the break points I saved were even bigger.”
Liberty Global is planning to acquire Belgian cable operator Telenet.Liberty Global, currently a majority shareholder of Telenet, has made an offer of €35 per ordinary share for the remaining stake in the operator. Through its wholly-owned subsidiary, Binan Investment, LG owns 50.4% of Telenet’s outstanding issued share capital.Mike Fries, President and chief executive officer of Liberty Global, said: “We believe this is the right time for Telenet to become a wholly-owned part of Liberty Global’s pan‐European platform in its next stage of development, particularly in light of the competitive and regulatory outlook in Belgium. We are proud of the success Telenet has achieved over the years and of the many innovations it has brought to Belgian consumers.”As a long‐term, industrial player in European cable, this shows our commitment to the Belgian market. Telenet is one of our most successful operations and a core part of our growing pan‐European platform. We remain very supportive of the existing management team and employees at Telenet, all of whom have contributed to the company’s success. We will continue our focus on investments and product innovation in Belgium.”The announcement came as Telenet said it had upwardly revisied its full year outlook. For the full year 2012, the operator now targets revenue growth of between 7-8% compared to between 5-6%, driven by growth in the number of multiple-play, digital TV, Sporting Telenet and Fibernet subscribers and a growing contribution from Telenet’s mobile telephony operations.At the end of June, 38% of Telenet’s subscribers took triple-play services. Digital TV subscribers numbered 1.472 million, up 17% year-on-year.
The South African government has decided not to make use of access control a mandatory feature of digital switchover in order to prevent further delays to the process.The government said that “use of a control system” would not be a mandatory feature of digital switchover but that government-subsidised boxes would have an access control system to protect the government’s investment.“To avoid challenges in implementing the digital migration programme, caused mainly by differences between broadcasters and also between some manufacturers, the use of a control system is not mandatory,” said the government’s revised policy statement. “However, the STBs will have a control system to protect government’s investment in the subsidised STB market and the local electronics industry and, with rapid technological changes, for future use by broadcasters who might not want to use it on implementation.”Broadcasters that want to use access control features on subsidised set-tops to deliver pay TV services will have to pay a fee to do so.Digital broadcasting will begin in South Africa by April 1 next year, with the date for analogue switch-off yet to be determined. The DTT signal must cover 84% of the country’s population by the launch date, with areas that are difficult to cover being reached by DVB-S2-based satellite broadcasting.
Global skinny bundle and direct-to-consumer revenues are set to grow eightfold to reach US$24 billion by 2023, according to Digital TV Research.According to the research outfit’s vMVPD and D2C TV Forecasts report, direct-to-consumer revenues are set for growth from US$1.3 billion last year to US$5.2 billion by 2023, while virtual MVPD or ‘skinny bundle’ revenues – will grow more three times more rapidly, up from US$2.8 billion last year to US$18.5 billion in 2023.Digital TV Research points out that vMVPD and D2C services are not mutually exclusive, with many vMVPD services providing access to direct-to-consumer platforms for an additional fee.According to the research, based on a study of 17 countries, the US will take the lion’s share of vMVPD revenues in 2023, accounting for US$12.34 billion or two thirds of the total. The only other country where skinny bundle revenues will pass the US$1 billion mark will be the UK, according to the research outfit.Simon Murray, Principal Analyst at Digital TV Research, said: “We forecast 77 million vMVPD subscribers by 2023, up from 21 million at end-2017. The US will contribute 28 million to the 2023 total, with India supplying 16 million.”Regarding direct-to-consumer OTT TV services, Digital TV Research predicts that such services will have 44 million subscribers by 2023, up from 14 million at the end of 2017. The US will account for 25 million D2C subscribers by 2023.
Reviewed by Alina Shrourou, B.Sc. (Editor)Feb 18 2019Genetic edits and protein restoration in mouse models of Duchenne muscular dystrophy remain viable one year after single CRISPR treatmentResearchers at Duke University have shown that a single systemic treatment using CRISPR genome editing technology can safely and stably correct a genetic disease — Duchenne muscular dystrophy (DMD) — for more than a year in mice, despite observed immune responses and alternative gene editing outcomes.The study appears online on February 18 in the journal Nature Medicine.In 2016, Charles Gersbach, the Rooney Family Associate Professor of Biomedical Engineering at Duke, published one of the first successful uses of CRISPR to treat an animal model of genetic disease with a strategy that has the potential to be translated to human therapy. Many additional examples have since been published, and several genome editing therapies targeting human diseases are currently in clinical trials, with more on the way.Gersbach’s latest research focuses on a mouse model of DMD, which is caused by the body’s inability to produce dystrophin, a long protein chain that binds the interior of a muscle fiber to its surrounding support structure.Dystrophin is encoded by a gene containing 79 protein-coding regions, called exons. If one or more exons are disrupted or deleted by an inherited mutation, the chain does not get built, causing muscle to slowly shred and deteriorate. Most patients are wheelchair-bound by age 10 and don’t live beyond their 20s or early 30s.Gersbach has been working on potential genetic treatments for Duchenne since 2009. His lab was one of the first to begin focusing on CRISPR/Cas9, a modified version of a bacterial defense system that targets and slices apart the DNA of invading viruses. His approach uses CRISPR/Cas9 to snip out dystrophin exons around the genetic mutation, leaving the body’s natural DNA repair system to stitch the remaining gene back together to create a shortened — but functional — version of the dystrophin gene.”As we continue to work to develop CRISPR-based genetic therapies, it is critical to test our assumptions and rigorously assess all aspects of this approach,” Gersbach said. “A goal of our experiments was to test some ideas being discussed in the field, which will help us understand the potential of CRISPR to treat genetic diseases in general and Duchenne muscular dystrophy in particular. This includes monitoring the long-term durability of the response in the face of potential immune responses against the bacterial Cas9 protein.”The first eight-week study demonstrated that functional dystrophin was restored and muscle strength increased. It did not, however, explore the long-term durability of the treatment.”It is widely believed that gene editing leads to permanent gene correction,” Gersbach said. “However, it’s important to explore theoretical possibilities that could undermine the effects of gene editing, such as losing treated cells or an immune response.”The goal of the new study was to explore factors that could alter the long-term effects of CRISPR/Cas9-based gene editing.Christopher Nelson, the post-doctoral fellow in Gersbach’s lab who led the work, administered a single dose of the CRISPR therapy intravenously to both adult and newborn mice carrying a defective dystrophin gene. Over the course of the following year, researchers measured how many muscle cells were successfully edited and what types of genetic alterations were made, as well as the generation of any immune response against the bacterial CRISPR protein, Cas9, which acts as the “scissors” that makes cuts to the genome.Other studies have reported that the mouse immune system can mount a response to Cas9, which could potentially interfere with the benefit of CRISPR therapies. Several groups have also reported that some people have preexisting immunity to Cas9 proteins, likely because of previous exposure to the bacterial host.Related StoriesNew gene-editing protocol allows perfect mutation-effect matchingResearchers develop new method to boost efficiency of CRISPR gene editing in DMDRussian researcher announces plans to create more CRISPR-edited babies”The good news is that even though we observed both antibody and T cell responses to Cas9, neither appeared to result in any toxicity in these mice,” said Nelson. “The response also did not prevent the therapy’s ability to successfully edit the dystrophin gene and produce long-term protein expression.”The results also suggested approaches to address potential challenges, should they arise in the future. For example, the researchers observed that when two-day-old mice without fully developed immune systems were treated intravenously, no immune response was detected. The CRISPR genome editing remained stable and, in some cases, even strengthened over the course of a year. One could imagine delivering the therapy to infants as a method of circumventing or modulating an unwanted immune response.Gersbach and Nelson acknowledge, however, that the mouse immune system often functions quite differently from the human immune system. And newborn screening for DMD is not currently widely performed; most Duchenne diagnoses occur when children are three to five years old. To address this challenge, Gersbach said suppressing the immune system during treatment may be a viable approach.The researchers are also investigating potential strategies to restrict the expression or delivery of Cas9 to only the muscle cells for short durations, which may lessen immune detection.”We were pleased to observe that all the mice were doing well a year after treatment, but our results show that there needs to be more focus on the immune response as we move toward larger animal models,” Nelson said.Nelson and Gersbach have previously investigated the potential of off-target editing by CRISPR/Cas9 to unintentionally modify other sites in the genome and reported minimal activity at likely off-target sites. Other recent studies, however, have reported that CRISPR can sometimes make genetic edits at the correct site but not in the intended manner. For example, some studies have shown that CRISPR can cut out genetic sections much larger than intended or that pieces of DNA can embed at the site of the cut. These types of edits had previously been unreported in genome editing studies because the methods being used only detected the intended edit.To comprehensively map all the edits occurring in the dystrophin gene, Nelson used a DNA sequencing approach that agnostically reports any type of edit. Surprisingly, there were many types of edits being made in addition to the intended removal of the targeted exon, including a high level of insertion of DNA sequences from the viral vector encoding the CRISPR/Cas9 system.Depending on the type of tissue and the dosage of CRISPR delivered, as many as half of the on-target edits resulted in these alternative sequence changes. Although this result was surprising, the unintended sequence changes do not appear to impact the safety or efficacy of this CRISPR/Cas9 gene editing approach for DMD.”None of these edits would necessarily be a cause for concern in this case because the dystrophin gene is already defective,” said Nelson. “That being said, any unintended results could potentially take away from the efficiency of the gene editing you’re trying to achieve, which supports the importance of designing ways to objectively identify and mitigate alternative edits in future studies.””Previous studies suggested that some of these other types of edits could happen,” Gersbach said. “But this is one of the first comprehensive measurements of these events in an animal model using a therapeutically relevant approach. Moving forward, this phenomenon needs to be monitored carefully and better understood. Methods that avoid these alternative edits and increase the frequency of the intended edit will be important to maximizing the potential of genome editing to treat disease.” Source:http://www.duke.edu/
By Dr. Liji Thomas, MDJul 8 2019Advanced colon cancer often spreads widely and may not respond to standard chemotherapy. In such a case, a novel combination of drugs and flexible dosing may help achieve a better outlook, as demonstrated by several new studies.In one study, investigators explored the use of paclitaxel in the treatment of metastatic squamous cell carcinoma of the anus. A 5-fluorouracil (5-FU)/cisplatin combination is the current first-line treatment for metastatic disease, but no standard therapy exists for refractory tumors (resistant to standard therapy). In this scenario, 6 patients were treated with paclitaxel, which is used in similar tumors of the head and neck. There was a measurable response to weekly treatment with paclitaxel in 4 patients, while one more showed stabilization of the disease following this therapy.The results of the European REARRANGE trial were presented at the ESMO World Congress on Gastrointestinal Cancer 2019. These were from almost 300 patients across Spain, Italy and France. These patients were 64 years old, on average, and all had refractory metastatic colorectal cancer (mCRC). All had progressed from first-line through fourth-line treatment for the disease.Regorafenib is a multi-kinase inhibitor used in refractory mCRC but with an unacceptably high rate of discontinuation due to severe adverse effects. The trial aimed to assess the effect of changes in the dosing schedule on the tolerability, toxicity and overall survival with this drug.Patients were randomly allocated to one of three groups: standard dose (SD), reduced dosing (RD) and intermittent dosing (ID). SD patients received 160 mg/day, while RD patients were on 120 mg/day, both for three weeks followed by a week off. In the ID group, regorafenib at 160 mg/day was used over alternate weeks. If cycle 1 of RD and ID treatment was tolerated well, all patients were switched to SD cycles thereafter. Guillem Agiles, study author, explains, “We reduced the dose in the first cycle and then escalated because it has been shown that the toxicity is higher in the first and second months of treatment.”While there was no change in the overall number of grade 3/4 adverse events, RD and ID use in the first couple of months was numerically associated with fewer adverse events that led to discontinuation, such as fatigue, hypertension and hand-foot skin reaction (HFSR. Treatment duration and median progression-free survival (about 3-4 months and 2 months respectively) were not affected, making this a viable alternative. The trial, which is the largest so far in this area, thus supported the use of flexible dosing with regorafenib in this condition.Agiles explains, “These results, interpreted in the context of other trials, like the American study ReDOS (3), tell us that the more flexible doses of regorafenib are an effective alternative in order to improve quality of life in patients with metastatic refractory colorectal cancer”. Other oncologists were equally impressed, with University Leuven professor Eric Van Cutsem predicting that it would change the way regorafenib is used in mCRC.Related StoriesStudy: Nearly a quarter of low-risk thyroid cancer patients receive more treatment than necessarySpecial blood test may predict relapse risk for breast cancer patientsNew protein target for deadly ovarian cancerThe ESMO congress also heard of another breakthrough: the BEACON CRC study on a combination of three drugs used to treat refractory mCRC positive for BRAF V600E-mutation. This mutation is observed in 15% of mCRC patients and has a poor prognosis.The trial involved 665 patients in three treatment groups: triplet therapy with encorafenib, binimetinib and cetuximab; doublet therapy with encorafenib and cetuximab; and one of two chemotherapeutic regimens (irinotecan or a combination of folinic acid, fluoruracil and irinotecan (FOLFIRI) with cetuximab).The triplet combination of non-chemotherapy agents was worked out to suppress both the BRAF kinase pathway and other compensatory mechanisms that allow tumor cells to develop resistance to BRAF inhihibitors. Study author Scott Kopetz commented: “Colorectal cancer does not respond to BRAF therapy alone because tumour cells adapt through other mechanisms after initial treatment. With this triple targeted therapy, we are using a very scientifically logical combination to inhibit BRAF and these other mechanisms.”The triplet therapy was well tolerated, and resulted in a median overall survival of 9 months, and objective response rate of 26% as against 5.4 months and 2% respectively with standard therapy. The striking improvement caused one expert to stress the need for routine BRAF testing in all patients with CRC henceforth, making this the new standard of care. “We now have a specific treatment that can change the natural course of the disease in patients with BRAF mutations and is better than previous therapy, so it is essential that patients are routinely tested,” said professor Andres Cervantes of Valencia.Moreover, the avoidance of chemotherapy is a big bonus. Cervantes says, “In many other types of cancer, and particularly in colorectal cancer, it is common for biological targeted therapies to be used in combination with chemotherapy. The fact that we can give this targeted combination without the need for chemotherapy is very good news for patients, not least because of the side effects that they typically experience with chemotherapy.”While only refractory mCRC patients who have failed up to two lines of chemotherapy are presently eligible for such treatment, it needs to be studied in other BRAF-mutant tumors, whether in earlier mCRC or adjuvant therapy following primary excision of the tumor, to enhance cure rates.The final word? Changing drug combinations and dosing schedules promise to make life better for mCRC patients while maintaining treatment efficacy. Sources: New Trial Demonstrates the Efficacy of a More Flexible Dose of Regorafenib to Relieve Side-effects in Patients with Metastatic Colon Cancer [ESMO World GI Press Release] – https://www.esmo.org/Press-Office/Press-Releases/ESMO-World-Congress-Gastrointestinal-Cancer-flexible-dose-regorafenib-colon-rearrange-argiles Targeted Therapy Combination Improves Survival in Patients with Advanced Bowel Cancer [ESMO World GI Press Release] – https://www.esmo.org/Press-Office/Press-Releases/ESMO-World-Congress-Gastrointestinal-Cancer-Encorafenib-Binimetinib-Cetuximab-Colorectal-BRAFV600E-Beacon-KopetzJournal reference:K Rekai, K Belkharoubi, B Larbaoui, P-001, Paclitaxel for the treatment of anal cancer after cisplatin and 5-fluorouracil, Annals of Oncology, Volume 30, Issue Supplement_4, July 2019, mdz155, https://doi.org/10.1093/annonc/mdz155
Explore further Twitter users may see reduced follower counts after changes made by the social network to stop tallying accounts which may have been compromised This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. Twitter to confirm new accounts in spam fight Twitter said Wednesday users are likely to see “follower” numbers drop as the service stops adding in potentially dubious or fraudulent accounts. The social network said it would make the change by removing from followers any accounts which have been “locked” after sudden changes in behavior, which may signal the people who opened them may no longer be in control.”This week, we’ll be removing these locked accounts from follower counts across profiles globally,” Twitter said in a blog post.”As a result, the number of followers displayed on many profiles may go down.”The San Francisco-based service said it reaches out to owners of locked accounts to confirm all is well and have them reset passwords.In the meantime, locked accounts were kept in tallies of other Twitter users they “followed.”Twitter said most of these accounts “were created by real people” but that it locks accounts if it cannot confirm that the original person who opened the account is still in charge.Twitter expected most users to see follower counts ebb by four or less, with “a more significant drop” for people with large follower numbers.”We understand this may be hard for some, but we believe accuracy and transparency make Twitter a more trusted service for public conversation,” the San Francisco-based company said.Reasons for accounts being locked include tweeting large numbers of unsolicited replies or firing off “misleading” links. Twitter said that it sometimes locks accounts if ranks of users block them, or if stolen passwords are posted online.”Until we confirm that everything is okay with the account, we lock it, which makes them unable to tweet or see ads,” Twitter said.”In most cases, these accounts were created by real people but we cannot confirm that the original person who opened the account still has control and access to it.”The impetus for the update was that follower counts often serve as an indicator of account credibility, according to Twitter. Citation: Twitter sweeps ‘locked’ accounts from follower tally (2018, July 11) retrieved 18 July 2019 from https://phys.org/news/2018-07-twitter-accounts-tally.html © 2018 AFP