The Australian Sports Commission (ASC) is seeking your support as a member of the Australian sport community, to join the ASC in promoting and participating in R U OK? Day. In doing so, you are helping to take a stance towards addressing mental health issues in sport. Every organisation can choose how they would like to be involved in R U OK? Day, all that is asked is that on Thursday, 7 October, you start a conversation with anyone who may be doing it tough and encourage your networks of athletes, coaches, employees and club members to do so as well. Our aim is to bring Australians together in a bid to help prevent the isolation that can lead to outcomes such as people taking their own lives.Staying connected with others is crucial to our general health and wellbeing. Feelings of isolation and being alone are major contributing factors to depression and social issues that can ultimately result in suicide. Regular, meaningful conversations can protect those we know and love.It’s so simple but in the time it takes to have a coffee, you can start a conversation that could change a life.For more information, please click on the following attachments, while the website can be found by clicking on the following link: http://www.ruokday.com.au/content/asc.aspx Related Filesruokday_poster-pdfruokday_overview_and_meeting_guide-pdf
Norwich defender Byram: Our team spirit is sky highby Freddie Taylora month agoSend to a friendShare the loveNorwich City defender Sam Byram is praising the chemistry and unity of the squad as they navigate the Premier League.The newly promoted side got a famous win against Manchester City at the weekend, despite several first team members being out with injury.Byram believes that aside from quality coaching and preparation, the camaraderie in the squad makes it easier for them to push to achieve their goals.”The character and spirit is definitely one of the best I’ve experienced,” he said to the club’s official website. “You can see from everyone, the players on the bench and the players that even weren’t on the bench, everyone wants the team to do well.”That’s the main thing for the unity. Not one player is bigger than the team and you can see that today with the work rate, everyone has got each other’s back.”We had a bit of luck throughout the game but we defended unbelievably well and also had spells in the game where we played some really good football.”We always have belief that we could win. It’s Manchester City and they are an unbelievable team but we’ve got a squad here which is very close-knit.”If someone drops out, someone else can fill in. You know exactly what your job is and I think we showed today the spirit we’ve got and how good we can be.” About the authorFreddie TaylorShare the loveHave your say
Private sector lender ICICI Bank on Thursday has reduced its base rate by 5 basis points (bps) to 9.7 percent with effect from 26 June, 2015. The bank’s new rate is equal to that of State Bank of India (SBI).ICICI Bank, which is India’s second largest bank in terms of market capitalization, had cut its base rate by 25 bps to 9.75 percent in April this year. Many banks had announced similar cuts in base rates in response to 25 bps cut in repo rate by the Reserve Bank of India (RBI) at its 2 June meeting.The first was SBI, which announced a 15 bps cut in base rate to 9.7 percent.Overall, the RBI has reduced the key rate by 75 bps since the beginning of the year.On 12 June, Finance Minister Arun Jaitley held a meeting with chiefs of various banks, asking them to pass on the benefits of the recent rate cuts by RBI to end users.Bank credit growth, a major indicator of economic growth, slowed to a two-decade low in the fiscal year ending March 2015. In 2014-15, credit growth was up 9.52 per cent, down from the 13.83 per cent increase in 2013-14.Bankers cite continued tight liquidity conditions and poor uptake in credit growth as reasons for the absence of higher cuts in lending rates.”With effect from July 1, 2010, interest rates on new loans and advances, including consumer loans, are determined with reference to I-Base (ICICI Bank Base Rate),” ICICI Bank said in a statement.
Fed Chair Says this is America’s #1 Threat [leaked in CA mtg] Imagine the secrets Fed chairwoman Janet Yellen is privy to: thwarted bank runs, interest rate spikes… the truth behind major swings in gold prices. So when she confessed America’s #1 risk at a private meeting in California, it’s no surprise word leaked out. She says this event could lead us into a “devastating spiral.” We at Casey Research believe it has already started. Click here for the full story. Recommended Links – — Companies are hiding more from you than you realize… Back in the late 90s, energy company Enron was a Wall Street darling. From 1998 to 2000, its stock surged 342%. It became America’s seventh biggest corporation…but the company was a farce. Management used shady accounting to inflate its sales and profits. When the fraud came to light, Enron’s stock plummeted. In 2001, it filed for bankruptcy. • In April, former Enron CEO Andy Fastow issued a serious warning… Fastow was one of the main actors in the Enron scandal. He spent six years in jail for his crimes. According to Fastow, many corporate executives are now doing what he did at Enron. He even accused tech giant Apple (AAPL) of misleading investors. Business Insider reported: His point – an entirely correct one – is that the world’s largest company today is engaged in tax dodging behavior that, while perhaps technically legal, is clearly designed to increase profits and inflate the stock by misleading and confusing regulators (and perhaps investors) via a massively complex web of entities – exactly what he did at Enron! And this is 100% routine, common behavior among most large US companies. Some people might find Fastow’s claim ridiculous. He is a convicted felon, after all. But Casey readers know better than to trust Corporate America. • Regulators have accused Valeant (VRX) and SunEdison (SUNE) of similar crimes… You’ve probably heard about the drug maker Valeant and the renewable energy company SunEdison. Their downfalls have been two of the year’s biggest investing stories. Like Enron, both companies were hot investments. From January 2013 to July 2015, Valeant gained 332%. SunEdison’s stock surged 892% over the same period. Like Enron, both companies used “creative accounting.” According to The Wall Street Journal, the Securities and Exchange Commission (SEC) is investigating whether “SunEdison misrepresented its cash position to investors as its stock collapsed.” Valeant is under investigation for its pricing and accounting practices. And like Enron, both stocks have crashed. SunEdison plunged 99% before it announced plans to file bankruptcy. Valeant’s stock has plummeted 89%. • The mainstream media paints Valeant and SunEdison as a couple “bad apples”… According to most reports, it’s rare for public companies to pull tricks on investors. But if you’ve been reading the Dispatch, you know that’s not true. For the past few months, we’ve been telling you about the huge surge in share buybacks. A share buyback is when a company buys its own stock from shareholders. Buybacks reduce the number of shares that trade on the market. This boosts a company’s earnings per share, which can lead to a higher stock price. But buybacks do not actually improve the business. They just make it look better “on paper.” According to research firm FactSet, 76% of the companies in the S&P 500 bought back their own shares between November and January. Most companies used debt to pay for these buybacks. The Wall Street Journal reported last week: The biggest 1,500 nonfinancial companies in the U.S. increased their net debt by $409 billion in the year to the end of March, according to Société Générale, using almost all—$388 billion—to buy their own shares, net of newly issued stock. Companies have become far and away the biggest customer for their own shares. • Companies are also using “financial engineering” to make their businesses appear healthier… Financial engineering is when companies use accounting tricks to goose their sales, profits, or cash on the balance sheet. It’s how Enron, Valeant, and SunEdison hid problems from investors. Many other companies are doing similar things… As you may know, U.S. corporations are required to report “GAAP” earnings per share. GAAP-based earnings comply with accepted accounting guidelines. A growing number of companies are also reporting “adjusted” earnings that do not comply with GAAP. Many companies use adjusted earnings to strip out “temporary” factors like the strong dollar or a warm winter. Management decides what to leave out and include when measuring adjusted earnings. • Two-thirds of the companies in the Dow Jones Industrial Average report adjusted earnings… In 2014, adjusted earnings were 12% better than GAAP earnings. Last year, they were 31% better. Companies say adjusted earnings give a more complete picture of their business. But it’s becoming obvious that companies are using non-GAAP earnings to hide weaknesses. As Dispatch readers know, the U.S. is in its weakest “recovery” since World War II. Europe, Japan, and China are all growing at their slowest pace in decades too. With the economy so weak, many companies have had to “get creative” to grow earnings. • Sales for companies in the S&P 500 have fallen four straight quarters… Earnings are on track to decline a fourth straight quarter. That hasn’t happened since the 2008-2009 financial crisis. These results would be even uglier if companies didn’t report adjusted earnings. You see, it’s much easier for companies to mask weak sales or profits when the economy is growing. When the economy slows, those problems become too big to hide. Right now, the global economy is clearly slowing. So expect to hear about more “Enrons” in the coming months. Regards, Justin Spittler Delray Beach, Florida May 10, 2016 We want to hear from you. If you have a question or comment, please send it to firstname.lastname@example.org. We read every email that comes in, and we’ll publish comments, questions, and answers that we think other readers will find useful. • The stock market is a dangerous place to put your money right now… If you’re going to invest in stocks, keep three important things in mind… You should avoid investing in businesses you don’t understand. Many hedge funds wish they had followed this advice with Valeant and SunEdison… Despite these companies’ complex and unclear business models, some of the largest hedge funds in the world invested in them. This earned Valeant and SunEdison the nickname “hedge fund hotels.” We also encourage you to avoid companies with a lot of debt. These firms will struggle to pay the bills as the economy worsens. Finally, we recommend you steer clear of companies that need buybacks to increase earnings. Buybacks can give stocks a temporary boost, but they’re no way to grow a business. In short, money spent on buybacks is money not spent on new machinery, equipment, or anything else that can help a company grow. It’s especially a poor use of cash when stocks are expensive…like they are today. • We encourage you to set aside cash and own physical gold… A cash reserve will help you avoid big losses during the next big selloff. It will also put you in a position to buy world-class businesses for cheap after the “rotten apples” are exposed. Physical gold is another proven way to defend your wealth. Gold has served as real money for centuries because it has a rare set of qualities: It’s durable, transportable, easily divisible, has intrinsic value, and is consistent across the world. It’s also protected wealth through the worst financial crises in history. Investors buy it when they’re nervous about stocks or the economy. This year, gold is up 22%. It’s at its highest level since January 2015. For other proven strategies to protect your money from a stock market crash, watch this short video. In it, you’ll learn how to fully “crisis proof” your wealth. Click here to view this free presentation. Chart of the Day The U.S. stock market is wobbling on one leg… Dispatch readers know buybacks have been a major driver of U.S. stocks. Since 2009, S&P 500 companies have shelled out more than $2 trillion on buybacks. As noted, buybacks can make earnings look better “on paper.” They can also prop up share prices. With the economy slowing and earnings in decline, buybacks have been one of the things keeping stocks afloat…but even that’s starting to give way. Today’s chart compares the performance of PowerShares Buyback Achievers Fund (PKW) this year versus the S&P 500. PKW tracks companies that bought back more than 5% of their shares over the past year. Holdings include McDonald’s (MCD), Lowes (LOWE), and Macy’s (M). From March 2009 to May 2015, PKW gained 314%. The S&P 500 rose 215% over the same period. Since then, PKW has fallen 10%. The S&P 500 is down 3%. Investors appear to be losing confidence in companies that buy a lot of their own stock. That’s a big problem for the stock market, which is showing major signs of weakness. Rickards: “Don’t Buy A Single Ounce Of Gold…” **This is an URGENT warning from Jim Rickards.** If you’ve seen the writing on the wall, like me, you know that gold could soon hit $10,000 per ounce. However, today I’m urging you NOT to buy a single ounce of gold till you read what I have to say. Click here for access to my urgent gold announcement.
Easy Search. Quality Finds. Your partner and digital portal for the cannabis community. Cannabis Industry Likely to Employ More Than 400,000 By 2021, Study Projects Next Article Guest Writer Cannabis The federal government shows few signs it will legalize one of the biggest job producers in the country. dispensaries.com Opinions expressed by Entrepreneur contributors are their own. Listen Now Image credit: Heath Korvola | Getty Images Green Entrepreneur Podcast –shares When it comes to projections, no sector of the economy currently has a rosier outlook than the marijuana industry.The latest report from ArcView Market Research demonstrates how big the numbers are getting. The name of the report neatly sums up the optimism of its findings: “U.S. Legal Cannabis: Driving $40 Billion Economic Output.”No one is questioning the potential for growth in the industry. Entrepreneurs have flocked to cannabis because of that potential. But there are headwinds, mostly involving an anti-marijuana U.S. attorney general, a White House administration that has largely stayed quiet on the issue and difficulties getting marijuana markets set up in some places even where voters have approved it.Still, in a release on the new report, ArcView CEO Troy Drayton said the economic potential of legal cannabis “is no longer just theory. Due to the giant impact adult-use legalization is already having in the United States, it’s vital for key stakeholders to understand the full impact of legalization, beyond just retail sales numbers.”So, what did the report find that impact would be?Related: Despite Being Illegal Under Federal Law, Cannabis Has Grown Into a $9 Billion Industry In States Where It Is Legal.California ImpactThe report was done against this backdrop: More than half of all U.S. states have approved a legal medical marijuana market, with adult-use marijuana sales are in place in Alaska, Colorado, Nevada, Oregon and Washington.California also started adult-use sales in January. Massachusetts is expected to start later this year. Lawmakers in Maine are still trying to work out a deal to get their adult-use market up and running, while New Jersey’s new Democrat governor has pledged to legalize marijuana in the Garden State.But California is the driver behind many positive projections. The biggest state in the union, California is expected to add billions to the marijuana market in the U.S.ArcView, which did the study with cannabis business intelligence company BDS Analytics, projects the marijuana industry in the U.S. will account for $39.6 billion in economic output by 2021. About 60 percent of that will come from just six states: California, Colorado, Massachusetts, Nevada, Oregon and Washington.The Golden State also is projected as a huge factor in another area: cannabis jobs.Related: Study Suggests Legal Pot Would Make Border Safer Than a Massive WallCannabis WorkersThe report projects that the California cannabis industry will add 99,000 jobs by 2021, about a third of all the cannabis-related jobs in the U.S. Indirect jobs related to the cannabis industry will total about 146,000 in the state.Other projections and findings from the report:The cannabis industry will create 414,000 jobs across the country by 2021, either directly in the cannabis industry or in a related job.State and local governments are projected to reap $4 billion in total tax receipts from the marijuana industry by 2021.The report argues that the legal recreational marijuana industry in Colorado may have led to the state having one of the lowest unemployment rates in the country.The total amount of taxes taken in by states where cannabis is legal reached $1 billion in 2016, including wholesale, excise and cannabis-specific sales taxes.Clearly, those numbers are a business person’s dream (government officials, too). The growing economic power of the legal marijuana industry might be the one thing that keeps it from coming under attack by the current administration in Washington.To stay up to date on the latest marijuana related news make sure to like dispensaries.com on Facebook February 15, 2018 3 min read Each week hear inspiring stories of business owners who have taken the cannabis challenge and are now navigating the exciting but unpredictable Green Rush. Add to Queue
Ashley Madison wants its users back.Sure, there was an embarrassing data breach last year. Sure, it wreaked embarrassment and devastation across its own user base. And sure there was the little matter of men paying subscription fees to talk with what turned out to be chat bots due to a startlingly low number of women users on the site. But that’s all water under the bridge. They’ve changed — transformed, even. And like any cheater worth his or her salt, the site is looking for a second chance.So it’s out with the old slogan — “life is short, have an affair” — and in with a new, risqué ad campaign.Is Ashley Madison’s new ad about hooking up at a hotel enough to restore people’s trust? https://t.co/4syldGRVgN— Entrepreneur (@Entrepreneur) July 12, 2016Related: Hackers Release the Personal Information of Adultery Seekers Who Joined Ashley MadisonIn one, a work-weary woman with a ho-hum other half ships off to a conference — only to bump into an interesting stranger.In another, a clock watcher with a terrible apartment and a worse shirt finds a rare ray of sunlight — a woman who smiles at him in the subway.And, in a third, a couple who seem polite, not passionate, meet an intriguing woman at a party.At the end of each of these inaugural ads for TV, Ashley Madison compels viewers to “Find Your Moment.” As before, cheating is a form of exploration. A sort of adventure. Don’t you want to seize the day? Ashley Madison certainly hopes so. The 47 million-member extramarital affair online hub took a deep, dark hit to its already controversial brand during last year’s hack and it’s still reeling from the damage. Key to its rebound isn’t just demand for affairs — but building back trust with users.Related: Court Rules FTC Can Come After Your Company After a Cyber AttackCuriously, Ashley Madison’s own ads remind users that cheaters don’t often need much help cheating. Every character in the company’s own ads finds new romantic friends in the usual spots — at hotels, parties and out and about. These folks don’t need the help of a digital platform that exposed millions of users, from pastors to government employees to low-level celebs. They did it on their own. DIY-style.Ashley Madison is hoping you won’t make that observation — and that its users can forget the past. So, what do you think? Will its seamy new TV spots be enough to restore trust in a platform built on breaking trust? (Or will it merely make you look a little closer at your spouse’s collar when he or she returns home from a business trip?) Do tell us via the Twitter poll above. Cheating Site Ashley Madison Is Back With an Ad Campaign We Don’t Understand Former West Coast Editor Next Article Image credit: Ashley Madison Online Dating July 14, 2016 Kim Lachance Shandrow 3 min read Add to Queue 80shares
Add to Queue For her new book, ‘Earning It,’ a WSJ journalist talked to 50-plus female corporate trailblazers about the experiences they had on their way up. Next Article We Didn’t Put a Woman in the White House. But What About Women in the Workplace? Image credit: Harper Collins Opinions expressed by Entrepreneur contributors are their own. –shares Women Leaders Joann S. Lublin November 9, 2016 9 min read Editor’s Note: On this day following the presidential election of 2016, many Americans are just starting to parse the pro and con messages about women that emerged from the two campaigns: One, the glass ceiling didn’t get broken, after all. And, two, how are women (and their men supporters) to think about the misogynistic talk that occurred in this election?Related: Sheryl Sandberg, Lean In 2.0 and Corporate Gender BiasGiven that reality, it’s perhaps especially appropriate today to feature an excerpt from the new book Earning It: Hard-Won Lessons from Trailblazing Women at the Top of the Business World, by Joann S. Lublin, a Pulitzer Prize-winning journalist and management news editor for The Wall Street Journal. Among the first female reporters at The Journal, Lublin faced uphill battles in her career, to become deputy bureau chief of the newspaper’s important London bureau, the first time it had been run by a woman. For her book, Lublin interviewed more than 50 women who had reached the highest rungs of the corporate ladder — across a diversity of industries, including retail, manufacturing, finance, high technology, publishing, advertising, automotive and pharmaceutical.Here is an excerpt from the chapter “Male Mentors Mean Business,” applicable to women in all workplaces, large or small . . .Countless women have seen their careers soar, thanks to help from a powerful senior executive. But some women paid a price for their close relationship with a male mentor. One such woman was Melissa Dyrdahl, the [former] chief executive of Ella Health, a health care start-up for women. She saw her career take off after Bruce R. Chizen, a former boss, hired her in 1994 to join Adobe Systems, the software maker, as a senior marketing manager. The two had developed a strong rapport at Claris, their former employer, and Dyrdahl assisted him in running a small new division of Adobe.“He knew exactly what he was getting from an employee standpoint,” Dyrdahl remembered. Chizen became her unofficial career coach at Adobe, offering insights about ways to excel in the male-dominated technology industry. Having a boss as a mentor helped Dyrdahl to get the respect she felt that she deserved, she said when we spoke. She saw that when professional challenges arose, Chizen and other senior Adobe men “always came in with an answer.”Because the two knew each other so well, “I’m brutally honest with her,” Chizen said in a Wall Street Journal article that I wrote about executive mentors. He also acted as Dyrdahl’s sponsor, an influential individual who opens the door of a promotion elevator and pushes a protégé through. During his climb to top management at Adobe, he brought along Dyrdahl and other valued mem-bers of his team. “I had someone who was highly respected, a more senior leader, making sure my name got put on the table,” Dyrdahl told me. With Chizen’s support, Adobe appointed her global vice president of marketing in 1998 and then advanced her to a senior vice presidency before elevating Chizen from president to CEO in late 2000. Once they both had reached the executive suite, Chizen and Dyrdahl occasionally drove to and from Adobe headquarters in San Jose together because they and their spouses lived near each other in suburban Los Altos. “We socialized together,” Dyrdahl recalled. “I know his kids. My husband has remodeled their house.” But as a result of these ties, the two high-profile executives encountered unexpected repercussions. One day, a human resources staffer at Adobe who was friends with Chizen and Dyrdahl strode into her office. “I just need to tell you, because nobody is going to tell you,” she said. “There’s people who think there’s something going on with you and Bruce.”The office gossip shocked Dyrdahl. Her jaw dropped, and “I was reeling,” she recollected. It suddenly dawned on her that she and Chizen now occupied a much more visible stage at the office. She quickly assured the human resources staffer that their relation-ship was purely professional. “I don’t want people to think I slept my way to the top,” Dyrdahl told her HR colleague.Driving home with Chizen soon after, Dyrdahl told him that coworkers wrongly perceived him as being something more than her supervisor and mentor. “They are only going to think badly of me,” she said. “Lots of things that we take for granted and we don’t think twice about, I can’t do anymore.”Chizen understood and accepted dramatic adjustments. They stopped driving together or going out for drinks unless a third person was present. “[I] never sat next to him in a meeting again,” Dyrdahl said. “I told him, ‘Unless there is no other chair, do not sit next to me.’”Even today, suspicions about an illicit affair sometimes arise when a male executive mentors or sponsors a female subordi-nate. For this reason, most senior-level men hesitate “to have one-on-one contact with a potential protégé who happened to be a younger woman,” said Sylvia Ann Hewlett in her 2013 book, (Forget a Mentor) Find a Sponsor: The New Way to Fast-Track Your Career. Her observations reflected research by the Center for Talent Innovation, a New York think tank that she heads and that studies issues in the workplace.This reluctance, Hewlett wrote, explains “why men are so much more likely to sponsor other men, inadvertently perpetuating the old boys’ club.” A 2010 study by her think tank found that men are 46 percent more likely to have sponsors than women. “Up-and-coming females tend to conclude that sponsorship, sexually fraught as it might be, is something they don’t actually need,” she said in her book.Hewlett considers that a dangerous assumption. Mentors build a woman’s self-esteem and serve as an empathetic sounding board, but sponsors expend valuable chips on a woman’s behalf and provide air cover so she can take risks. “Sponsors, not mentors, put you on the path to power and influence by affecting three things: pay raises, high-profile assignments, and promotions,” she wrote.Other researchers support Hewlett’s argument. More than half of senior executive women said having a higher-level sponsor is extremely important, yet women have less access to senior male staffers who could assist with their careers, concluded a 2015 study by LeanIn.Org, founded by Sheryl Sandberg, and McKinsey. The research tracked women’s progress at 118 North American companies. A handful of corporate programs designate workplace advocates for managerial women. At least nine big businesses have set up sponsorship initiatives that match promising female leaders with sponsors or teach such women how to attract a sponsor, I wrote in an advice column on careers published on WSJ.com in 2011. American Express Co., for example, launched its “Pathways to Sponsorship” program that year for twenty-one female senior vice presidents at the major financial services company. By the end of 2014, 25 percent of those initial participants had been promoted and 45 percent had made strategic lateral moves, an American Express spokeswoman told me. The company has also expanded its sponsorship effort to cover a wider range of managerial levels.Yet formal mentoring and sponsorship programs remain far out of reach for most professional women. Only 30 percent of all American professionals have access to such programs, and there is a smaller proportion of women than men within that group, according to a 2014 survey of 1,005 adults by Edward Jones, a financial services firm. Just 18 percent of the women allowed to participate in these programs actually do, the poll showed, compared with 21 percent of the men.Men on Women’s SideMale mentors and sponsors played crucial parts in the careers of numerous corporate executives I interviewed. “At the end of the day, men still hold most of the power,” suggested Sandra “Sandi” Peterson, the group worldwide chairman of Johnson & Johnson. “So you better have male mentors.”But as is evident from Dyrdahl’s experience, women must make sure that their relationships with higher-level men don’t raise eyebrows among coworkers. To further refute false rumors about any romantic entanglement with Chizen, she stopped her habit of flying alone with him on commercial flights for business travel.In Dyrdahl’s view, things haven’t improved for women since she left Adobe in late 2006. These days, she encourages women to take steps that clarify their ties with a male mentor so the relationship cannot be misconstrued by colleagues. “You give up your power when you wittingly or unwittingly put yourself in situations where people perceive you as having an affair and getting something because of your sex,” she pointed out. “I felt I had to work twice as hard because I was blond and attractive.”Related: For Women in Tech, Bias Runs Deeper Than Most Think Management News Editor, The Wall Street Journal Free Webinar | Sept 5: Tips and Tools for Making Progress Toward Important Goals Attend this free webinar and learn how you can maximize efficiency while getting the most critical things done right. Register Now »
Reviewed by James Ives, M.Psych. (Editor)Jan 29 2019Researchers have been struggling for years to find a treatment for patients who have a recurrence of acute myeloid leukemia (AML), an aggressive blood cancer that is one of the most lethal cancers. About 19,520 news cases are diagnosed a year, and about 10,670 people a year die from it, according to the American Cancer Society.Purdue University researchers are developing a series of drug compounds that have shown promise in treating such cases. About 30 percent of AML patients have a mutation caused by a kinase called FLT3, which makes the leukemia more aggressive. Inhibitors of FLT3, such as Radapt, approved last year by the U.S. Food and Drug Administration, have shown good initial response to treating leukemia. Gilteritinib, another FLT3 inhibitor, was recently approved toward the end of 2018. But AML patients on FLT3 inhibitor therapy often relapse because of secondary mutations in the FLT3 and existing treatments have not been fully successful in treating those cases.Researchers on a team led by Herman O. Sintim, the Drug Discovery Professor of Chemistry in Purdue’s Department of Chemistry, say they have developed a series of compounds that work not only on AML with common FLT3 mutation, but also drug-resistant AML harboring problematic mutations, such as the gatekeeper F691L mutation, which some leukemia patients who relapse harbor.”These compounds have a great potential to be the next-generation AML therapeutics for relapsed patients who no longer respond to first- or second-generation FLT3 inhibitors,” Sintim said.The results of the study were published Friday here in the journal EBioMedicine.The research aligns with Purdue’s Giant Leaps celebration, recognizing the university’s global advancements made in health, longevity and quality of life as part of Purdue’s 150th anniversary. This is one of the four themes of the yearlong celebration’s Ideas Festival, designed to showcase Purdue as an intellectual center solving real-world issues.Results of the study are encouraging because, while advancements have been made in many other forms of cancer over the past three decades, advancement for AML has been slow.AML, which accounts for only about 1 percent of all cancers, occurs when blood cells fail to mature or differentiate and multiply unchecked, causing a lack of adequate oxygen-carrying red blood cells. AML is uncommon before the age of 45, but it does occur in children. The five-year survival rate is about 30 percent, and for patients over the age of 65, the five-year survival rate is less than 10 percent.Related StoriesStudy shows how SIRT1 plays key role in maintaining the regenerative potential of leukemic stem cellsImmune-boosting compound could make pancreatic cancers susceptible to immunotherapyResearchers discover biochemical agent responsible for blood pressure drop in sepsisThe compounds the Purdue researchers are studying, alkynyl aminoisoquinoline and alkynyl napthyridine, have been successful in preclinical studies, Sintim said. “In mouse studies, almost no leukemia burden was visible after compound treatment for only a few weeks. Crucially this new class of FLT3 inhibitor also works against drug-resistant secondary mutations, such as the problematic F691L mutatio,” Sintim said.In the clinic, the goal is to reduce leukemia levels enough so that a patient can undergo a bone marrow transplant. Most often if the leukemia burden is not drastically reduced before bone marrow transplant, there is a high likelihood that the AML will return.Sintim said the compounds the researchers are developing have shown no signs of toxicity. Observations in clinical testing show that high doses of the compounds result in no weight loss, irritability or essential organs dysfunction. Another advantage of the compounds the Purdue researchers are developing is they can be taken orally, which makes it easier for patients to take at home compared with an injection.Sintim said there’s much still to be learned about AML.”Acute myeloid leukemia is not caused by only one mutation. It’s caused by many mutations. What that means is that you might have an acute myeloid leukemia patient who would have one type of a mutation and you could have another one with another type of mutation and you cannot give them the same drug. Even when a patient initially presents with one type of mutation, during treatment a new mutation could emerge” he said. “So to effectively treat a cancer you need to know what the aligning mutation is, this is what is called precision medicine; tailoring a drug to a particular disease driver.”Sintim also is a co-founder of a biotech startup called KinaRx LLC, which has licensed the compounds the researchers are working on through Purdue’s Office ofTechnology Commercialization. Both Sintim’s lab and KinaRx LLC are looking for development partners. Source:https://www.purdue.edu/newsroom/releases/2019/Q1/drug-compound-could-be-next-generation-treatment-for-aggressive-form-of-leukemia.html
Much of the research led by CD4 director Pia Vogel and Wise is centered on a class of proteins called ABC transporters, a key factor in why many cancers resist chemotherapy.”These transporters are defensive proteins and are normally very, very good for us. They protect us from toxic chemicals by literally pumping them out of the cell, almost like a sump pump removes water from one’s cellar,” Vogel said.But when someone has cancer, these proteins do more harm than good.”One protein, P-glycoprotein, can pump nearly all chemotherapeutics out of the cancer cell, thereby making the cancer resistant to many drugs and untreatable,” Wise noted.For this reason, SMU researchers tested the combination of using an inhibitor that temporarily shuts down P-glycoprotein’s ability to remove drugs from the cancer cells along with chemotherapeutics on prostate cancer cells grown in the lab, which have been shown to be resistant to multiple chemotherapeutic drugs.Related StoriesLiving with advanced breast cancerVirus killing protein could be the real antiviral hero finds studyNew study to ease plight of patients with advanced cancerThe SMU team was able to show that if inhibitors of P-glycoprotein are used during and after the multidrug resistant cancer cells have been exposed to the chemotherapy drugs, then the cancer cells become much more sensitive to the chemotherapeutics.The recipe for success was giving cancer cells a dose of both chemotherapy drugs and the P-gp inhibitor for just two hours. Researchers then washed the prostate cancer cells to get rid of any residual chemotherapy drugs before giving the cells another dose of just P-gp inhibitor for 22 hours, lead author and SMU Ph.D. doctoral candidate Amila K. Nanayakkara explained.Prostate cancer cells that were given this treatment were shown to retain chemotherapy drugs at a much higher level compared to cancer cells not treated with the P-glycoprotein inhibitor. After about 24 hours, much fewer of these cancer cells survived in this treatment compared to the cells which had not seen the inhibitor.When the same tests were performed on normal noncancerous cells, “there was no sign of extra toxicity to the healthy cells using this method,” Wise added.One issue, though, is how to duplicate this method in a patient’s body. “Once you’ve taken a chemotherapy drug, it’s not easy to remove it after just two hours,” said co-author Vogel, a professor in the SMU Department of Biological Sciences.Still, the researchers argued that it is worth further research, because there are currently few options for cancer patients once their disease becomes resistant to multiple chemotherapies.”Our paper shows these remarkable effects when the inhibitor is present during, and importantly, after exposure to chemotherapeutic,” Wise said. “And while ‘washing’ is not feasible in humans, the kidneys and other organs are in a sense doing the washing step for a patient. These organs are washing the chemotherapy from the bloodstream and therefore, out of cancer cells. So in that way, we think our preliminary cell culture studies may be translatable at least in principle to animals and people.” Reviewed by James Ives, M.Psych. (Editor)Jun 10 2019Researchers at SMU’s Center for Drug Discovery, Design and Delivery (CD4) have succeeded in lab testing the use of chemotherapy with a specific protein inhibitor so that the chemotherapeutic is better absorbed by drug-resistant cancer cells without harming healthy cells. The approach could pave the way for a more effective way to treat cancers that are resistant to treatment.A mix of drugs is frequently used to shrink cancer tumors or keep tumor cells from spreading to other parts of the body. But chemotherapy is so toxic that the mix often kills healthy cells, too, causing dreadful side effects for cancer patients. And eventually, many cancers learn how to resist chemotherapy, making it less effective over time. When multidrug resistance evolves, this leaves the patient with a very poor prognosis for survival and the oncologist with few, if any, effective tools, such as chemotherapy medicines, to treat what is very likely an aggressive and/or metastatic cancer at this point.”John Wise, associate professor in the SMU Department of Biological Sciences and co-author of a study on the findings published in PLOS ONE Source:Southern Methodist University
Originally published on Live Science.by Taboolaby TaboolaSponsored LinksSponsored LinksPromoted LinksPromoted LinksYou May LikeVikings: Free Online GamePlay this for 1 min and see why everyone is addicted!Vikings: Free Online GameUndoTruthFinder People Search SubscriptionOne Thing All Liars Have in Common, Brace YourselfTruthFinder People Search SubscriptionUndoTop 10 Best Meal DeliveryMeal Kit Wars: 10 Tested & Ranked. See Who WonTop 10 Best Meal DeliveryUndoFinance101What Are The Best States To Retire In?Finance101UndoBirch Gold GroupThis IRS Tax Law is Sweeping the U.S.Birch Gold GroupUndoAnti-Snoring SolutionA Simple Fix for Snoring And Sleep ApneaAnti-Snoring SolutionUndo 5. The moon is two-faced (probably because of a massive asteroid). Ours is a moon with two faces: the nearside boasts a thinner and smoother crust, while the farside crust is thicker and dotted by impact craters left nearly undisturbed by lava flows. The discrepancies have vexed scientists for decades, and in a new paper, researchers use models to explore what may be possible explanations for the stark differences. They argue that those distinctive sides could be the result of a giant impactor slamming into the moon and leaving a massive crater across the entire nearside. [Read more about what created the moon’s two faces.] Discover more fascinating facts about the moon with BBC America’s “Wonders of the Moon,” premiering Friday, July 19 at 10 p.m. EDT/9 p.m. CDT. 3. The moon is shrinking and quaking. The moon is shrinking. And as the crust of our lone satellite contracts, it tugs on cliff-like cracks on the surface, leading to lots of moonquakes, researchers have discovered. Scientists revisited moonquake data gathered from 1969 to 1977 by seismic equipment on the Apollo lunar missions. They mapped the seismic data to satellite images of thrust faults, or scarps — stairstep cliffs on the lunar surface. These formations stand dozens of feet high and extend for miles, and they are visible in images captured by NASA’s Lunar Reconnaissance Orbiter. The researchers discovered that around 25% of the moonquakes were likely generated by released energy from these faults, rather than by asteroid impacts or activity deep inside the moon. Scarps are spread across the face of the moon in a vast, global network, and are estimated to be no more than 50 million years old, the researchers wrote. The age and distribution of the scarps hint that they appeared as the moon’s interior cooled down, causing its crust to contract. [Read more about the moonquakes] A stunning shot of the 2017 total solar eclipse as soon from the Armstrong Flight Research Center at Edwards Air Force Base in California. Credit: Carla Thomas/NASA/BBC America A burnt-orange moon hangs over London. Although scientists have unraveled many of the moon’s mysteries in the 50 years since Apollo 11, mankind’s enchantment with our nearest neighbor has never dimmed. Credit: James Burns/BBC America The International Space Station’s incredible view of the moon. Credit: Luca Parmitano/BBC America 2. There’s an enormous, dense blob of metal below the surface of the moon’s south pole. Deep below the moon’s South Pole-Aitken basin (the largest preserved impact crater anywhere in the solar system), researchers have detected a gargantuan “anomaly” of heavy metal lodged in the mantle that is apparently altering the moon’s gravitational field. According to a study of the mysterious blob, published April 5 in the journal Geophysical Research Letters, the anomaly likely weighs somewhere in the neighborhood of 2.4 quadrillion tons (2.18 quintillion kilograms). The researchers aren’t sure how this giant blob of metal got itself trapped below the lunar surface. Simulations suggest it could be the heavy remnants of the iron-nickel asteroid that crashed into the far side of the moon and created the giant South Pole-Aitken crater some 4 billion years ago. [Read more about the massive blob beneath the moon.] Gallery: The Fantastic Full Moon See Spectacular Lunar Mission Images in 3D (Photos) A beautiful bright moon illuminates Brecon Beacons National Park in Wales, UK. Credit: Allyn Wallace/BBC America 1. There is water on the moon, and it jumps around. In 2009, data from NASA’s Lunar Reconnaissance Orbiter (LRO) led to the discovery of water on the moon locked up in ice. A recent upgrade to the orbiter, called the Lyman Alpha Mapping Project (LAMP), has allowed scientists to take a closer look at the water on the lunar surface. LAMP has revealed that water molecules move around the moon as the lunar surface warms and cools throughout the day. Water remains stuck on the moon’s surface until the lunar midday, when some of the water melts and heats up enough to lift into the moon’s delicate atmosphere. The water floats around a bit until it reaches an area cool enough to make it settle back down to the surface.Advertisement Water on other planetary bodies could be a valuable resource for human explorers to not only drink but also to serve as fuel for future robotic exploration, since water can be split to form rocket fuel, saving missions from having to carry that fuel from Earth. [Read more about how water hops around the moon.] Find Apollo 11 Landing Site While Skywatching The MoonFor the 50th anniversary of humanity’s first steps on the lunar surface, learn 5 facts about our moon and where to find the Apollo 11 landing site while viewing it in the night sky. Credit: NASA/JPL-CaltechVolume 0%Press shift question mark to access a list of keyboard shortcutsKeyboard Shortcutsplay/pauseincrease volumedecrease volumeseek forwardsseek backwardstoggle captionstoggle fullscreenmute/unmuteseek to %SPACE↑↓→←cfm0-9接下来播放Better Bug Sprays?01:33关闭选项Automated Captions – en-US facebook twitter 发邮件 reddit 链接https://www.livescience.com/65943-strange-facts-about-the-moon.html?jwsource=cl已复制直播00:0003:1903:19Your Recommended Playlist01:33Better Bug Sprays?04:24Sperm Whale Befriends Underwater Robot01:08Why Do French Fries Taste So Bad When They’re Cold?00:29Robot Jumps Like a Grasshopper, Rolls Like a Ball02:31Surgical Robotics00:29Video – Giggly Robot关闭 Photos: Mysterious Objects on the Moon It’s been almost 50 years since a human first set foot on the moon. Since then, our knowledge about Earth’s closest neighbor has improved by leaps and bounds, and our obsession with it has never waned. Witness some of the most amazing images of the moon ever recorded and be reminded of the significant influence of our moon in BBC America’s new documentary “Wonders of the Moon,” premiering Friday, July 19 at 10 p.m. EDT/9 p.m. CDT. As the world begins its commemoration of the awe-inspiring first walk on the lunar surface, let’s review five of the most recent and fascinating scientific findings about the moon. 4. You won’t strike it rich on the moon. Gold, platinum and other metals known as highly siderophile (“iron-loving”) elements are far more abundant in Earth’s crust than they are in its natural satellite. That may seem odd, given the two worlds’ shared history. About 4.5 billion years ago, a Mars-size planet dubbed Theia slammed into the proto-Earth, blasting huge amounts of material from both bodies into space. Some of this liberated stuff was incorporated into the bruised and battered Earth, and some coalesced to form the moon. But highly siderophile elements (HSEs) appear to have been left out of the mix. These metals were likely delivered by later asteroid strikes — but why does Earth have so much more than the moon? The researchers suspect that the moon’s weaker gravitational pull means material delivered via impact isn’t as likely to have stayed on the moon as it did on Earth — lots of stuff that hits the moon returns to space. The small concentration of HSEs retained on the moon likely arrived before the moon’s magma ocean cooled and solidified, so the material became incorporated into the moon’s core. [Read more about why Earth has way more gold than the moon.]
politics Published on In 1999, when Atal Bihari Vajpayee took charge as prime minister, he would begin his first and only five-year tenure in the office. His previous two terms, in the midst of political instability, lasted only 13 days and 13 months, respectively.Eight years after the reforms of 1991, the Indian economy was only beginning to find its way. Vajpayee was faced with the prospect of having to take some tough decisions to ensure investor confidence and stability to the economy. Although he led a coalition government, Vajpayee did not hesitate to undertake the reforms.Privatisation of government enterprises — not just their disinvestment — was a key Vajpayee government initiative. He brought in legislation to cap fiscal deficit, and rolled out reforms to fund manager UTI, ushered in a new telecom policy, and masterminded the Golden Quadilateral highways. A look at each in detail. PrivatisationIf selling government shareholding in central public sector enterprises (CPSEs) — what Jawaharlal Nehru called the ‘temples of modern India’ — was not easy, privatising them was a distant dream. However, Vajpayee, along with his Disinvestment Minister Arun Shourie, not just offloaded equity in some of the CPSEs but successfully managed to privatise companies such as Maruti, BALCO, Hindustan Zinc, Modern Foods and VSNL. Besides, the Vajpayee Government offloaded minority stake in many other CPSEs, such as ONGC, IOCL and GAIL, that yielded over ₹20,500 crore for the government.Managing the fiscThe first National Democratic Alliance government enacted a new law, the Fiscal Respsonsibility and Budget Management (FRBM) Act, to keep the fiscal deficit under 3 per cent. The FRBM Act aimed to introduce transparent fiscal management systems in the country, a more equitable and manageable distribution of the country’s debts over the years, and fiscal stability in the long run. Though successive governments deferred bringing the fiscal deficit to the 3 per cent level, it still brought about more responsibility and accountability. The Act also prescribed three documents as part of the Budget documents: a Medium Term Fiscal Policy Statement, a Fiscal Policy Strategy Statement, and a Macro-economic Framework Statement. These documents have helped in understanding fiscal situations and planning the way ahead.The UTI scamAfter the US-64 scam came into light, the Vajpayee government took steps not just to bifurcate fund manager Unit Trust of India (UTI), but also came out with guidelines for the entire mutual fund (MF) industry. Most important was the ban on assured returns on investment in MF schemes. This brought more clarity for the investors, and also restored confidence.The rural focusIt was a common understanding that urban India enjoyed the fruits of the reform initiatives of 1991, and that Bharat, or the rural population, lagged behind. In order to remove this perception, the Vajpayee government launched ambitious road projects such as the Golden Quadrilateral network of highways and the Pradhan Mantri Gram Sadak Yojna. The Golden Quadrilateral connected the four metros of Chennai, Kolkata, Delhi and Mumbai through a network of highways, while the PMGSY was planned as a network of all-weather roads for unconnected villages. Both projects proved to be immense successes, and not only contributed to the growth story, but also bridged the gap between India and Bharat.New ring to telecomThe New Telecom Policy of 1999 transformed the country’s telecom industry. The fixed-license fee regime was replaced with a revenue-sharing arrangement. The Bharat Sanchar Nigam Ltd (BSNL) was carved out of the Department of Telecommunications to separate policy formulation from services. The creation of the Telecom Dispute Settlement Appellate Tribunal (TDSAT) also separated the government’s regulatory role (performed by the Telecom Regulatory Authority of India) and its dispute-settlement roles. The government ended the monopoly of the Videsh Sanchar Nigam Ltd on international telephony and allowed private firms to offer the ISD facility.Even today, many an economic discussion seems to hinge on these challenges only: no strategic disinvestment has happened since then; the telecom policy seems to be undergoing constant change; and managing fiscal deficit remains a challengeVajpayee was a master in delegating responsibilities, says a former top official who served in a key economic ministry during the NDA rule. Whether it was on the international stage, or within the country, Vajpayee’s ministers did not shy away from taking decisions. The strength of economy was also on show when, even after sanctions were imposed in the wake of the nuclear test in Pokhran, India survived without begging, said another officer. COMMENT people RELATED death When Vajpayee steadfastly said ‘Nothing doing’ for a Bharat Ratna SHARE SHARE EMAIL The Vajpayee government liberalised the economy further, and gave a new direction to infrastructure The peacemaker departs August 16, 2018 SHARE COMMENTS
Navjot Singh Sidhu – THE HINDU SHARE SHARE EMAIL SHARE people COMMENT June 06, 2019 Under fire from Chief Minister Amarinder Singh for Congress’ “poor performance” in urban areas in the Lok Sabha election, Punjab minister Navjot Singh Sidhu, on Thursday, skipped the first Cabinet meeting after elections and asserted he could not be “taken for granted”.Amarinder had recently said he intended to change the cricketer-turned-politician’s portfolio — Local Government Department — over the party’s performance.“I cannot be taken for granted. I have been a performer throughout the 40 years of my life. Be it international cricket, or world class commentary with Geoffrey Boycott, TV shows or motivational talks,” Sidhu told reporters.He said the urban areas had played pivotal role in the party’s victory in Punjab and his department is being singled out.“My department is being singled out publicly. I always regard him as my elder and listen to him. But it hurts. Where is the collective responsibility now? He (Amarinder) could have called me and said anything he wanted to say,” Sidhu said here.In the recently held general election, Congress won eight out of the 13 seats. The SAD-BJP combine won four while the AAP managed to win just one seat. COMMENTS Published on politics