When it comes to everything digital, we often learn by doing or by watching someone wow us with a trick. Here are five of my favorites that are high on the functional side.
When it comes to everything digital, we often learn by doing or by watching someone wow us with a trick. Here are five of my favorites that are high on the functional side.
When we are in the phase of finding our purpose in life; it isn’t always as clear as day. This article will guide you through steps that will help you find your purpose here on earth.
A lot of people are good at what they do. Some are even elite. A select few are completely unstoppable.
Those who are unstoppable are in their own world. They don’t compete with anyone but themselves. You never know what they will do — only that you will be forced to respond. Even though they don’t compete with you, they make you compete with them.
Are you unstoppable? By the end of this blog you will be.
Let’s get started:
1. Don’t think — know and act.
“Don’t think. You already know what you have to do, and you know how to do it. What’s stopping you?” — Tim Grover
Rather than analyzing and thinking, act. Attuned to your senses, and with complete trust in yourself, do what you instinctively feel you should. As Oprah has said, “Every right decision I have ever made has come from my gut. Every wrong decision I’ve made was the result of me not listening to the greater voice of myself.”
The moment you start thinking, you’ve already lost. Thinking swiftly pulls you out of the zone.
2. Always be prepared so you have the freedom to act on instinct.
“Just as the yin-yang symbol possesses a kernel of light in the dark, and of dark in the light, creative leaps are grounded in a technical foundation.” — Josh Waitzkin
Become a master of your craft. While everyone else is relaxing, you’re practicing and perfecting. Learn the left-brained rules in and out so your right brain can have limitless freedom to break the rules and create.
With enhanced consciousness, time will slow down for you. You’ll see things in several more frames than others. While they’re trying to react to the situation, you’ll be able to manipulate and tweak the situation to your liking.
3. Don’t be motivated by money or anything external.
Having nice things is, well, nice. But for you, it’s never been about the money, prestige or anything else outside of you. Take these things away and nothing changes for you. You’re still going to be pushing your personal limits and giving it your all. Give these things to you and they won’t destroy you like they do most people.
4. Never be satisfied.
“The drive to close the gap between near-perfect and perfect is the difference between great and unstoppable.” — Tim Grover
Even after you achieve a goal, you’re not content. For you, it’s not even about the goal. It’s about the climb to see how far you can push yourself.
Does this make you ungrateful? Absolutely not. You’re entirely humbled and grateful for everything in your life. Which is why you will never get complacent or lazy.
To quote Jim Rohn, “the way to enjoy life best is to wrap up one goal and start right on the next one. Don’t linger too long at the table of success, the only way to enjoy another meal is to get hungry.”
5. Always be in control.
Unlike most people, who are dependent on substances or other external factors, you are in control of what you put in your body, how you spend your time and how long you stay in the zone.
Act based on instinct, not impulse. Just because you could doesn’t mean you do. And when you do, it’s because you want to, not because you have to.
6. Be true to yourself.
Although 70 percent of US employees hate their jobs and only one in three Americans report being happy, relentless and unstoppable people purge everything from their life they hate.
Have the self-respect and confidence to live life on your terms. When something isn’t right in your life, change it. Immediately.
7. Never let off the pressure.
“Pressure can bust pipes, but it also can make diamonds.” — Tim Grover
Most people can handle pressure in small doses. But when left to their own devices, they let off the pressure and relax.
Not you. You never take the pressure off yourself. Instead, you continuously turn-up the pressure. It’s what keeps you alert and active.
8. Don’t be afraid of the consequences of failure.
Most people stay close to the ground, where it’s safe. If they fall, it won’t hurt that bad. But when you choose to fly high, the fall may kill you. And you’re OK with that. To you, there is no ceiling and there is no floor. It’s all in your head. If something goes wrong — if you “fail” — you adjust and keep going.
9. Don’t compete with others. Make them compete with you.
Most people are competing with other people. They continuously check-in to see what others in their space (their “competition”) are doing. As a result, they mimic and copy what’s “working.”
Conversely, you’ve left all competition behind. Competing with others makes absolutely zero sense to you. It pulls you from your authentic zone. So you zone out all the external noise and instead zone in to your internal pressure to produce.
10. Never stop learning.
Ordinary people seek entertainment. Extraordinary people seek education and learning. When you want to become the best at what you do, you never stop learning. You never stop improving and honing your skills and knowledge.
Your unparalleled preparation is what gives you power. No one else is willing to pay the price you’ve paid.
11. Success isn’t enough — it only increases the pressure.
For most people, becoming “successful” is enough. However, when you’re relentless, success only increases the pressure to do more. Immediately following the achievement of a goal, you’re focused on your next challenge.
12. Don’t get crushed by success.
“Success can become a catalyst for failure.” — Greg McKeown
Most people can’t handle success, authority or privilege. It destroys them. It makes them lazy. When they get what they want, they stop doing the very things that got them there. The external noise becomes too intense.
But for you, no external noise can push harder than your own internal pressure. It’s not about thisachievement, but the one after, and the one after that. There is no destination. Only when you’re finished.
13. Completely own it when you screw up.
“Implementing extreme ownership requires checking your ego and operating with a high degree of humility. Admitting mistakes, taking ownership and developing a plan to overcome challenges are integral to any successful team.”―Jocko Willink
No blame. No deception or illusion. Just the cold hard truth. When you mess up, you own it. And as the leader, you own it when your team fails. Only with extreme ownership can you have complete freedom and control.
14. Let your work speak for itself.
“Well done, is well said.” — Anthony Liccione
Cal Newport’s recent book, Deep Work, distinguishes “deep work” from “shallow work.” Here’s the difference:
Deep work is:
And non-replicable (i.e., not easy to copy/outsource)
Shallow work is:
Replicable (i.e., anyone can do it)
Talking is shallow. Anyone can do it. It’s easily replicated. It’s low value. Conversely, deep work is rare. It’s done by people who are focused and working while everyone else is talking. Deep work is so good it can’t be ignored. It doesn’t need words. It speaks for itself.
15. Always work on your mental strength.
“Mental resilience is arguably the most critical trait of a world-class performer, and it should be nurtured continuously. Left to my own devices, I am always looking for ways to become more and more psychologically impregnable. When uncomfortable, my instinct is not to avoid the discomfort but to become at peace with it. My instinct is always to seek out challenges as opposed to avoiding them.” — Josh Waitzkin
The better you can be under pressure, the further you’ll go than anyone else. Because they’ll crumble under pressure.
The best training you will ever do is mental training. Wherever your mind goes, your body follows. Wherever your thoughts go, your life follows.
16. Confidence is your greatest asset.
You’ve heard it before: Running a marathon is far more mental than physical. A person’s ability to run a marathon — or do anything hard — is more a reflection of their level of confidence than their actual ability.
Your confidence determines:
The size of challenges/goals you undertake
How likely you will achieve those goals
How well you bounce back from failures
If you’re not confident, you will never put yourself out there in the first place. When you’re confident, you don’t care how many times you fail, you’re going to succeed. And it doesn’t matter how stacked the odds seem against you.
17. Surround yourself with people who remind you of the future, not the past.
When you surround yourself with people who remind you of your past, you’ll have a hard time progressing. This is why we get stuck in certain roles, which we can’t break free from (e.g., the fat kid or shy girl).
Surrounding yourself with people who you want to be like allows you a fresh slate. You’re no longer defined by your past, only the future you are creating.
18. Let things go, but never forget.
Being unstoppable requires carrying no unnecessary mental or emotional baggage. Consequently, you’ll need to immediately and completely forgive anyone who has wronged you. However, forgiveness doesn’t mean you forget. And it doesn’t mean you have to do further business with those who have wronged you.
19. Have clear goals.
“While a fixation on results is certainly unhealthy, short-term goals can be useful developmental tools if they are balanced within a nurturing long-term philosophy.” — Josh Waitzkin
According to loads of psychology research, the most motivating goals are clearly defined and time-bound.
Your goals can either be focused on your behaviors (e.g., I’m going to write 500 words per day) or on the outcomes you’re seeking (e.g., I’m going to get published on The New York Times by June 1, 2016).
For most people, behaviorally-focused goals are the better and more motivating option. But when you crave the results so much that the work is irrelevant, your aim should be directed straight at the outcomes you want. However, results-focused goals are better when short-term and grounded in your long-term vision and philosophy. When your why is strong enough, the how will take care of itself.
20. Respond immediately, rather than analyzing or stalling.
“He who hesitates is lost.” — Cato
Anticipation of an event is always more extreme than the event itself — both for positive and negative events.
Just do it. Train yourself to respond immediately when you feel you should do something. Stop questioning yourself. Don’t analyze it. Don’t question if it came from God or from yourself. Just act.
You’ll figure out what to do after you’ve taken action. Until you take action, it will all be hypothetical. But once you act, it becomes practical.
21. Choose simplicity over complication.
“If you can’t explain it simply, you don’t understand it well enough.” — Albert Einstein
It’s easy to be complicated. Most of the research and jargon in academia and business is over-complicated.
Cutting to the core and hitting the truth is hard, because it’s simple. As Leonardo da Vinci has said, “Simplicity is the ultimate sophistication.”
Very few people will give you the truth. When you ask them a question, it gets mighty complicated. “There are so many variables” or “It depends” they say.
T. S. Eliot said it best, “Where is the wisdom we have lost in knowledge? Where is the knowledge we have lost in information?”
Wisdom is timeless and simple. Learn wisdom and choose it.
22. Never be jealous or envious of someone else’s accomplishments.
Being unstoppable means you genuinely want what’s best for everyone — even those you would consider your competitors. Jealousy and envy are the ego — which operates out of fear.
The reason you are happy for other people’s success is because their success has nothing to do with you.
You are in control of you. And you are different from every other person. There is no one who can do exactly what you can do. You have your own superpower with your own unique ability to contribute. And that’s what you’re going to do.
23. Take the shot every time.
“If I fail more than you, I win.” — Seth Godin
You miss every shot you don’t take. And most people don’t want to take the shot. Fear of failure paralyzes them.
The only way you can become unstoppable is if you stop thinking about it. Just take the shot. Don’t do it only when it’s convenient or when you feel ready. Just go and make whatever adjustments you need after the fact.
24. Don’t get caught up in the results of your success. Always remain focused on what got you those results: the work.
When you start doing noteworthy stuff, there are benefits that can become distractions. It can get easy to “ride the wave” of your previous work. Keep practicing. Perfect your craft. Never forget what got you here.
25. Think and act 10X.
“When 10X is your measuring stick, you immediately see how you can bypass what everyone else is doing.” — Dan Sullivan
Most people — even those you deem to be “world class” — are not operating at 10X. In truth, you could surpass anyone if you radically stretch your thinking and belief system.
Going 10X changes everything. As Dan Sullivan has said, “10X thinking automatically takes you ‘outside the box’ of your present obstacles and limitations.” It pulls you out of the problems most people are dealing with and opens you to an entirely new field of possibilities.
When you take your goal of earning $100,000 this year and change it to $1,000,000, you’re forced to operate at a different level. The logical and traditional approach doesn’t work with 10X. As Shane Snow, author of Smartcuts: How Hackers, Innovators, and Icons Accelerate Success,has said, “10x progress is built on bravery and creativity instead. Working smarter.”
The question is: Are you willing to go there? Not just entertain the thought for a second or two and then revert back to common thinking. No. Are you willing to sit with 10X thinking? Are you willing to question your own thought processes and open yourself to believing an entirely different set of possibilities?
Could you convince yourself to believe in your 10X potential? Are you willing to undertake goals that seems lunacy, to you and everyone else? Are you willing to take the mental leap, trusting “the universe will conspire to make it happen”?
26. Set goals that far exceed your current capabilities.
“You need to aim beyond what you are capable of. You need to develop a complete disregard for where your abilities end. If you think you’re unable to work for the best company in its sphere, make that your aim. If you think you’re unable to be on the cover of TIME magazine, make it your business to be there. Make your vision of where you want to be a reality. Nothing is impossible.” — Paul Arden
If your goals are logical, they won’t force you to create luck. Being unstoppable means your goals challenge you to be someone more than you currently are. As Jim Rohn has said, “Don’t wish it was easier, wish you were better.”
27. Make time for recovery and rejuvenation.
“Wherever you are, make sure you’re there.” — Dan Sullivan
When you focus on results, rather than being busy, you’re 100 percent on when you’re working and 100 percent off when you’re not. This not only allows you to be present in the moment, but it allows you the needed time to rest and recover.
Your ability to work at a high level is like fitness. If you never take a break between sets, you won’t be able to build strength, stamina and endurance. However, not all “rest” produces recovery. Certain things are more soothing than others.
Recovering from my work generally consists of writing in my journal, listening to music, spending time with my wife and kids, preparing and eating delicious food, or serving other people. These things rejuvenate me. They make my work possible, but also meaningful.
28. Start before you’re ready.
“The best time to plant a tree was 20 years ago. The second best time is now.” — Chinese Proverb
Most people wait. They believe they can start after they have enough time, money, connections and credentials. They wait until they feel “secure.” Not people who are unstoppable.
Unstoppable people started last year. They started five years ago before they even knew what they were doing. They started before they had any money. They started before they had all the answers. They started when no one else believed in them. The only permission they needed was the voice inside them prompting them to move forward. And they moved.
29. If you need permission, you probably shouldn’t do it.
A mentor of mine is a highly successful real estate investor. Throughout his career, he’s had hundreds of people ask him if they should “go into real-estate.”
He tells every one of them the same thing: that they shouldn’t do it. In fact, he actually tries talking most of them out of it. And in most cases he succeeds.
Why would he do that? “Those who are going to succeed will do so regardless of what I say,” he told me.
I know so many people who chase whatever worked for other people. They never truly decide what they want to do, and end up jumping from one thing to the next — trying to strike quick gold. And repetitively, they stop digging just a few feet from the gold after resigning the spot is barren.
No one will ever give you permission to live your dreams.
30. Don’t make exceptions.
Zig Ziglar used to tell a story of traveling one day and not getting in bed until 4 a.m. An hour and a half later (5:30), his alarm went off. He said, “Every fiber of my being was telling me to stay in bed.” But he had made a commitment, so he got up anyway. Admittedly, he had a horrible day and wasn’t productive at all.
Yet, he says that decision changed his life. As he explains:
“Had I bowed to my human, physical, emotional and mental desire to sleep in, I would have made that exception. A week later, I might have made an exception if I only got four hours of sleep. A week later, maybe I only got seven hours of sleep. The exception so many times becomes the rule. Had I slept in, I would’ve faced that danger. Watch those exceptions!”
Hence, Zig was unstoppable.
“From this point, your strategy is to make everyone else get on your level, you’re not going down to theirs. You’re not competing with anyone else, ever again. They’re going to have to compete with you. From now on, the end result is all that matters.” — Tim Grover
When you’re unstoppable, you will make sure to get what you want. Everything you need to know is already within you. All you need to do is trust yourself and act.
Are you unstoppable?
Article by: Benjamin P. Hardy
He’s the emotional and tactical anchor of the Warriors, and now he’s proven he can be a liability.
It wasn’t a matter of how, but when. Draymond Green, who has spent these playoffs administering nut-shots, mugging at opponents, and racking up technical fouls, has been suspended for Game 5, following an incident with LeBron James that, at this point, should surprise no one. It’s a serious blow to the Warriors, who despite being up 3-1 are heading back to Oakland with Stephen Curry banged-up (perhaps requiring off-season surgery) and Green watching from an undisclosed location. In the Thunder series, we saw that it was possible to overpower the Warriors. Now, the team is operating at a genuine deficit.
Green’s suspension, inevitable as it may have seemed, points to a larger problem: The player who anchors the Warriors both tactically and emotionally has proven that he can be a liability. For most of the regular season, Green was bold and defiant without detracting from the Golden State’s effectiveness. But in the playoffs, Draymond Green has occasionally lost control. And for the Warriors, this might be a problem beyond winning this year’s title.
It’s hard to reconcile Draymond Green. He’s the quintessential scrappy, do-whatever-it-takes role guy, but he’s also one of the most skilled players in the league. He’s everywhere at once on the floor, but he’d never be mistaken for a futuristic, position-less freak. He’s both a triumphant underdog and the face of the Warriors’ perceived arrogance. He’s both a product of the system and arguably its single most important piece. He’s a relentless competitor who can’t help but resort to low blows in the heat of the moment. Draymond Green, who has such utter command of the game of basketball, can still lash out in desperation.
Yet Green, for all his contradictions, rarely fails to get the job done. Curry and Klay Thompson can be frighteningly streaky; Green, on the other hand, reliably chugs along, keeping the team afloat at both ends of the court, making plays while his two high-scoring teammates wait around to get hot. Decoding Draymond Green is almost beside the point because he’s so damn effective. Green isn’t just the glue that holds the Warriors together, he’s their insurance. As long as he’s on the floor, Golden State—who over the course of the playoffs, have gone from indestructible to beset by doubt—will be some semblance of their 73-9 selves. The so-called “Line-Up of Death,” which puts Green at center, isn’t just the signal best example of the team’s innovative thinking—it’s a virtual showcase for everything that makes Green so special.
“Curry and Klay Thompson can be frighteningly streaky; Green, on the other hand, reliably chugs along, keeping the team afloat at both ends of the court, making plays while his two high-scoring teammates wait around to get hot.”
What this suspension reminds us, though, is that the Green—and the Warriors’—story is still very much unfolding and it’s never quite added up. The Warriors went from unlikely champions to world-historic force in a single season. Stephen Curry, already an All-Star, took it upon himself to redefine the way time and space work on a basketball court. Green went from a curiosity to one of the game’s few indispensable players. And as has already been said a thousand times, in the playoffs we’ve seen them both learn to lose and—depending on how you see the relationship between perception and reality in sports—either “turn heel” or finally face an unavoidable backlash.
The lingering doubts about the Warriors’ legitimacy have less to do with bullshit claims about the relative competitiveness of NBA eras and more to do with the sheer strangeness of their rise. The Green suspension is only the latest quirk: On the verge of a championship, he simply couldn’t resist playing like an asshole. Golden State’s reliance on an unstable isotope is a high-stakes gamble that has finally blown up in their face. That’s not to in any way diminish Draymond’s sheer talent or his overall value. But the degree to which Golden State depends on Green—something that tonight’s game will shed much light on—might itself be a problem. This team doesn’t need Green pushing limits or hedging against utter bedlam; this isn’t a Russell Westbrook-like situation where a player’s outlandish tendencies are exactly what make him so valuable. Draymond Green doesn’t have to be a deal with the devil. You can imagine a version of him who didn’t constantly risk shooting his team in the foot.
Through much of the season, that’s the player we were watching. Apparently, though, Green was barely keeping himself in check all along. That’s been one of the great revelations of the playoffs, and given how important Draymond is to this team, it raises all sorts of questions about the Warriors going forward. If Green’s distractions become a habit, how exactly are the Warriors supposed to sustain a dynasty? Can Steve Kerr, who lucked out on his first coaching gig, effectively manage Green and his moods? Has success made a monster out Draymond Green, with meltdowns and prima donna-ish behavior just lurking on the horizon?
It’s really impossible to say, and we probably won’t know for sure until the 2016-17 season. One thing’s for certain: The Warriors are a team whose identity is still in flux and Draymond Green is central to almost all of the ever-shifting narratives around the team. His volatility has turned Golden State into a moving target, a work-in-progress whose past performance means very little as long as he continues to show up in new, interesting, and potentially damaging ways. It’s almost too obvious to call Green the heart and soul of the Warriors. He’s way more than that. He’s the one we look to when trying to figure out what exactly this team means—and where exactly they are headed.
BY: BETHLEHEM SHOALS
Researchers have had promising results treating tumours with everyday medicines. So why aren’t the big pharma companies investing in trials
Helen Hewitt lost her mother, her younger brother and her baby son to cancer. Having successfully overcome breast cancer herself, she is currently battling several tumours in her lungs, and – thanks to an inherited mutation in her DNA – is at high risk of developing other cancers as well. Yet Helen, 41, is pioneering an unfamiliar approach against this all too familiar foe. Alongside conventional chemotherapy, surgery, and radiotherapy, she is taking a cocktail of experimental yet well-known medicines. Some of them might even be in your bathroom cabinet.
One is the diabetes drug metformin, which besides making healthy cells more sensitive to the effects of the hormone insulin may also help to starve sugar-hungry cancer cells. The cholesterol-lowering statin and the antibiotic she’s been prescribed have the added benefit of dampening inflammation – a process cancer cells use to help them grow. Then there’s mebendazole, a common treatment for threadworm, which may also inhibit the growth of the blood vessels to her tumours.
Helen sought out these drugs after undergoing surgery to remove one tumour from her lung, only to discover that a different tumour had set up offshoots there as well. “It just made sense to try something that might weaken the tumours but wasn’t going to have a big impact on me in terms of side effects,” says Helen, an NHS podiatrist who lives inWolverhampton.
An early success story is thalidomide, whose resurrection as a cancer drug began in the 90s
Although the jury is still out on whether such drugs really make a difference, these aren’t the only medicine cabinet stalwarts undergoing a makeover. From aspirin to antacids, beta blockers to ibuprofen, all are being reinvestigated and utilised as potential anti-cancer drugs.
Unlike older therapies, which directly target and destroy dividing cancer cells, many of these repurposed drugs appear to work by targeting the healthy cells that cancers team up with to support their growth. Though widely accepted, this view of cancer as a mixture of deranged and healthy cells is still relatively new – which in part explains why the anti-cancer properties of drugs like aspirin may have been missed the first time around. “When many of these drugs were developed, we had a very simplistic view of cancer and all the focus was on finding ways of killing cancer cells,” says Pan Pantziarka, joint coordinator of the Repurposing Drugs in Oncology project, which aims to identify the most promising medicines for adaptation and get them into clinical trials. “But the whole system depends on developing a supporting blood supply, subverting the immune system, and producing certain growth factors. A lot of these repurposed drugs address these other things that cancer is dependent on to survive.”
An early success story is the controversial drug thalidomide. Originally developed as a sedative during the 1950s, it was later used to curb morning sickness during pregnancy, until it was found to increase the risk of severe birth defects and confined to the scrapheap. Thalidomide’s resurrection as a cancer drug began in the 90s, following the discovery that it inhibited the growth of new blood vessels. A series of case reports also indicated that it might suppress the immune system. Angus Dalgleish, a professor of oncology at St George’s hospital in Tooting, London, became interested in the drug after witnessing the dramatic turnaround of a patient with autoimmune disease who was treated with thalidomide. “I started doing some more reading and it struck me that here was a gem that had been thrown out with the rubbish,” he says. At around the same time, the results of a small trial of thalidomide in patients with the bone marrow cancer myeloma were published. The patients had failed to respond to standard therapy and were given thalidomide as a last resort; a quarter of them saw a reduction in their cancer as a result. But thalidomide had other side effects besides the awful deformities it generated in foetuses. So working with a startup company called Celgene, Dalgleish helped to develop several less toxic analogues, which were put into clinical trials. One of them was lenalidomide, today a blockbuster myeloma drug, which generates around $4bn in worldwide sales per year.
For now at least, thalidomide stands alone as a successfully repurposed anti-cancer drug. But it could soon be joined by aspirin, which has already taken on a new guise as a treatment for heart attacks and stroke. “There’s now some very interesting evidence suggesting that it might be a useful anti-cancer drug as well,” says Ruth Langley, a medical oncologist at the MRC Clinical Trials Unit in London. She is currently recruiting for a clinical trial of aspirin in around 11,000 patients who have already undergone the best available treatment for breast, colorectal, gastro-oesophageal or prostate cancer. “We are trying to see if, by giving aspirin, we can either delay the cancers coming back or even prevent them coming back altogether,” Langley says.
The idea comes from previous observations that people who take aspirin to prevent heart attacks seem to have lower rates of cancer than the general population, and if they do develop cancer it’s less likely to spread to other organs. Aspirin acts on particles in the blood called platelets and makes them less sticky. This reduces the likelihood of blood clots, which is why it’s used to treat cardiova scular disease. One theory is that platelets also surround cancer cells as they travel around the body, making them less visible to the immune system, but they do this less efficiently if someone is taking aspirin. Another theory is that platelets help cancer cells to anchor in new sites and set up new tumours.
Several trials are under way around the world, investigating the use of the beta-blocker propranolol (more commonly used to treat high blood pressure) in breast, ovarian and other cancers. These follow the discovery that propranolol can be used to treat non-cancerous birthmarks called haemangiomas – also known as strawberry marks – in children. “We said to ourselves, if it works in haemangioma, these drugs must inhibit the growth of blood vessels, so they could be useful to treat cancer too,” says Nicolas André, a paediatric oncologist at Hôpital de La Timone Enfants in Marseilles, France, who is about to start a trial of propranolol in angiosarcoma – a cancer of the lining of blood vessels.
And there are other candidates. The ReDo project has drawn up a list of the six most promising drugs based on their low toxicity, plausible mechanism of action and strong evidence of potential efficacy in humans. They are: the aforementioned anti-worm drug mebendazole; an antacid used to treat stomach ulcers called cimetidine; the angina drug nitroglycerin; a broad-spectrum anti-fungal called itraconazole; an antibiotic used to treat chest infections called clarithromycin; the anti-inflammatory painkiller diclofenac.
Yet despite the excitement surrounding these drugs, getting them into clinical trials is a long and arduous process. Unlike thalidomide, whose anti-cancer properties were spotted relatively early by someone with the clinical contacts to quickly move things forward, many of these drugs have been ignored, despite preliminary human trials with encouraging results.
Why is this? Surely pharma companies should be jumping up and down at the prospect of an effective, low toxicity cancer drug – particularly when the number of new cancer cases is projected to increase by 70% worldwide over the next two decades. In the UK alone, the number of people living with cancer is predicted to rise to 4 million by 2030, compared with 2.5 million currently. The trouble is that many of the existing drugs showing promise as anti-cancer agents have already lost their patents. “A drug company that invests money in supporting a clinical trial is not guaranteed to recoup that money if the trial is successful because some other manufacturer could come in and sell the same drug at a lower price,” says Pantziarka. “It’s a return-on-investment question.” Where clinical trials of these drugs have been done, they’ve generally been conducted by doctors and small groups of investigators. “They don’t have the time, experience or the money to take their positive results and change practice,” Pantziarka adds.
Ironically, their low cost is one reason repurposed drugs are such an attractive prospect. The average cost of new cancer drugs has increased from around £70 per month in the 1990s to more than £7,000 per month today; if this trajectory continues then we can expect the first £70,000 a month cancer drug by 2035, says Paul Cornes, an oncologist at the Bristol Oncology Centre. Part of the reason they’re so expensive is because it takes years of testing to ensure that any new treatment is safe and effective. But with repurposed drugs, many of these questions have already been answered. “We know they’re relatively safe, because they’re widely used,” says André. “Even so, we need sound, state-of-the-art clinical trials to confirm they work in cancer, and in order to get those we need funding.”
With investment from big pharma lacking, some groups are coming up with creative ways of getting these drugs into clinical trials. In November, doctors at St George’s hospital used crowdfunding to raise £50,000 to test the benefits of the anti-malarial drug artesunate on 140 patients with colorectal cancer. In an earlier pilot study of 20 patients, the cancer spread in six of the 11 given a placebo, compared with just one of the nine given artesunate. In this case, the drug appears to kill cancer cells directly, and it costs just 70p per day.
One of the huge advantages of using repurposed drugs is that you have a lot of toxicity information available already
Despite promising results like these, it could still be years before we know for sure if repurposed drugs work against cancer, and if so, how best to use them. But unfortunately, time is a luxury many cancer patients can’t afford. This has prompted some to take matters into their own hands.
One of them is Ben Williams, an experimental psychologist at the University of California in San Diego, who was diagnosed with an extremely aggressive brain cancer called a glioblastoma in 1995, aged 50. He immediately underwent surgery, and then radiotherapy, but his prospects looked bleak: the average life expectancy for patients with glioblastoma is just 15 months, with younger people more likely to survive. Williams expected to die within the year.
With little left to lose, he started searching for other drugs that might complement the chemotherapy he was about to start, using the biomedical literature database PubMed. This provided published studies of alternative glioblastoma treatments, many of which were repurposed drugs. When he identified a relevant-looking drug, he’d contact the researchers directly, asking for further information and advice about taking it. “Part of my strategy was that I needed to make the chemotherapy more effective, because it didn’t work most of the time,” says Williams. “If you’ve got a lethal diagnosis, then you’re going to have to take some risks to beat it.”
As a result, he started taking a cocktail of drugs more commonly prescribed for acne, insomnia and high blood pressure, as well as the breast cancer drug tamoxifen, which early studies had suggested might help to overcome resistance to chemotherapy. His oncologist was unimpressed. “He said, ‘you’re going to hurt yourself’, but I knew that I was less likely to hurt myself doing this than taking some of the stuff that he was offering,” says Williams, who travelled to Mexico to buy some of the drugs he wanted. “I was very much aware of the risks. But one of the huge advantages of using repurposed drugs is that you have a lot of toxicity information available already, because they have been used for such a long time.”
In Williams’s case, his treatment worked; against the odds, he remains cancer-free to this day. But even he admits he may have just got lucky and been one of the minority who responds well to chemotherapy: “I will never know whether any of these things I took made a big difference, and neither will anyone else.”
However, there are good reasons why cancer patients should talk to their doctors, rather than self-medicating – even with something as seemingly innocuous as aspirin. “Firstly, we don’t know if it works, and secondly, even though aspirin is a very common drug, there are side effects,” says Langley. “There is a small risk of bleeding from your gut, or more seriously, even from your brain. We need to do proper studies and monitor safety very carefully.”
The same goes for other common medicines that may or may not have anti-cancer effects. “Even if they are effective, they are drugs that you probably need to take for long periods of time to see the effect – otherwise their effects would have been recognised before,” Langley adds.
Pantziarka, too, advises patients to work with their doctors rather than go it alone – and also certainly not to see repurposed drugs as an alternative to conventional treatments.
“When we supply information to people, we encourage them to talk to their medical teams; we do not encourage them to go off and self-medicate.”
But not all doctors are open to new approaches, as Pantziarka knows only too well. He first became interested in the idea of drug repurposing when his teenage son, George, was diagnosed with terminal cancer in his jaw bone. Like Williams, he started researching published trials for his son’s condition on PubMed and then directly contacting the clinicians who had run them. The suggestions they came back with included a diabetes drug called pioglitazone, and another anti-inflammatory painkiller called celecoxib, in combination with continuous low doses of chemotherapy.
“My son’s doctor was not very positive,” Pantziarka says. “She said, ‘We don’t have any experience of these drugs’, and the argument that millions of people take pioglitazone for diabetes had no sway.” Eventually, she suggested a different combination of drugs, based on a protocol another doctor at her hospital had used previously. It was ineffective, and only made George feel worse. He died in April 2011, aged 17.
Doctors are understandably cautious about prescribing drugs for unlicensed uses; their peers may think them strange, and they may also find themselves in trouble if something goes wrong. But Dalgleish is one of those who is prepared to take these risks. He prescribes repurposed drugs for some of his cancer patients, and also liaises with their GPs and asks them to prescribe them, where appropriate. “I’ve had a lot of hassle for that,” he says. “There’s no room for freedom to do the best thing for your patients, just because someone hasn’t put up millions of pounds to do a big drugs trial.”
This is something that should at least partly be addressed with the Access to Medical Treatments Act which gained royal assent in March. It empowers the health secretary to create a database of innovative medical treatments, including off-label uses of existing drugs for cancer and other diseases. However, doctors still won’t be protected against medical negligence claims should something go wrong.
“It aims to raise awareness of the off-label use of repurposed drugs, to combat concerns about prescribing them and to ensure that they are used more consistently by clinicians,” says Nick Thomas-Symonds, Labour MP for Torfaen, who campaigned for it.
The government has also agreed to have information about the off-label use of drugs included in the British National Formulary – the pharmaceutical reference book used by doctors when prescribing medicines – and to develop an action plan to make it easier to gain new licences for drugs when they’re proven to be effective.
Helen Hewitt also found her NHS oncologist unwilling to prescribe the repurposed drugs she’d identified, so she found a private clinic in London where she could get them instead. She has been taking them since September, but last month she received disappointing news: the tumours in her lung have grown bigger. The next step is chemotherapy – something she’s been through before, but this time she’ll be taking her cocktail of non-cancer medications at the same time. “My hope, and the possibility, is that taking these drugs will weaken the tumour, so that when I do have chemotherapy there’s a better chance of it having an effect,” she says.
Her hope isn’t necessarily misplaced. If repurposed drugs do work, most experts agree they’re more likely to do so in combination with other drugs, rather than on their own. “I don’t believe in magic bullets; they are going to be part of combinations, and since they are fairly non-toxic and inexpensive you could use several agents more easily than when using standard drugs,” says André.
One of the problems with tumours is that they evolve, and most new cancer drugs are directed against a single molecular target. “Basic evolutionary biology tells us that cancer is a complex, adaptive system that evolves resistance to very closely targeted agents,” says Pantziarka. An advantage of these older, repurposed drugs is that they often hit multiple targets. Take diclofenac: it is often viewed as a relatively dirty drug because besides dampening pain and inflammation, it can irritate the stomach and slightly raise the risk of heart attacks and stroke. However, it may also inhibit the growth of blood vessels, modulate the immune system, and make the body more sensitive to the effects of radiotherapy and chemotherapy. It might be cheap and dirty, but that’s a lot of bang for a single tablet. Patients certainly shouldn’t see repurposed drugs as a panacea, but they’re at least worthy of hope.
By: Linda Geddes
For more key trends go check out Daily Key Knowledge
When it comes to identifying heart disease in midlife, Dr. Nissen says there are a lot of “strange myths” floating around.
Keeping tabs on your blood’s cholesterol and triglyceride levels is really the only hard-and-fast measure of future heart trouble, he says.
Still, research has turned up a handful of odd symptoms that might—emphasis on might—predict heart disease later in life.
While experiencing one of these symptoms is no reason to freak out, consider them a good reminder to go see your doctor about your cholesterol and triglyceride levels, which Dr. Nissen says every adult should have a handle on.
One way to think about work-life balance issues is with a concept known as The Four Burners Theory. Here’s how it was first explained to me: Imagine that your life is represented by a stove with four burners on it. Each burner symbolizes one major quadrant of your life.
The Four Burners Theory says that “in order to be successful you have to cut off one of your burners. And in order to be really successful you have to cut off two.”
My initial reaction to The Four Burners Theory was to search for a way to bypass it. “Can I succeed and keep all four burners running?” I wondered.
Perhaps I could combine two burners. “What if I lumped family and friends into one category?”
Maybe I could combine health and work. “I hear sitting all day is unhealthy. What if I got a standing desk?” Now, I know what you are thinking. Believing that you will be healthy because you bought a standing desk is like believing you are a rebel because you ignored the fasten seatbelt sign on an airplane, but whatever.
Soon I realized I was inventing these workarounds because I didn’t want to face the real issue: life is filled with tradeoffs. If you want to excel in your work and in your marriage, then your friends and your health may have to suffer. If you want to be healthy and succeed as a parent, then you might be forced to dial back your career ambitions. Of course, you are free to divide your time equally among all four burners, but you have to accept that you will never reach your full potential in any given area.
Essentially, we are forced to choose. Would you rather live a life that is unbalanced, but high-performing in a certain area? Or would you rather live a life that is balanced, but never maximizes your potential in a given quadrant?
What is the best way to handle these work-life balance problems? I don’t claim to have it figured out, but here are three ways of thinking about The Four Burners Theory.
We outsource small aspects of our lives all the time. We buy fast food so we don’t have to cook. We go to the dry cleaners to save time on laundry. We visit the car repair shop so we don’t have to fix our own automobile.
Outsourcing small portions of your life allows you to save time and spend it elsewhere. Can you apply the same idea to one quadrant of your life and free up time to focus on the other three burners?
Work is the best example. For many people, work is the hottest burner on the stove. It is where they spend the most time and it is the last burner to get turned off. In theory, entrepreneurs and business owners can outsource the work burner. They do it by hiring employees.
In my article on The 3 Stages of Failure, I covered Sam Carpenter’s story about building business systems that allowed him to work just 2 hours per week. He outsourced himself from the daily work of the business while still reaping the financial benefits.
Parenting is another example. Working parents are often forced to “outsource” the family burner by dropping their children off at daycare or hiring a babysitter. Calling this outsourcing might seem unfair, but—like the work example above—parents are paying someone else to keep the burner running while they use their time elsewhere.
The advantage of outsourcing is that you can keep the burner running without spending your time on it. Unfortunately, removing yourself from the equation is also a disadvantage. Most entrepreneurs, artists, and creators I know would feel bored and without a sense of purpose if they had nothing to work on each day. Every parent I know would rather spend time with their children than drop them off at daycare.
Outsourcing keeps the burner running, but is it running in a meaningful way?
One of the most frustrating parts of The Four Burners Theory is that it shines a light on your untapped potential. It can be easy to think, “If only I had more time, I could make more money or get in shape or spend more time at home.”
One way to manage this problem is to shift your focus from wishing you had more time to maximizing the time you have. In other words, you embrace your limitations. The question to ask yourself is, “Assuming a particular set of constraints, how can I be as effective as possible?”
This line of questioning pulls your focus toward something positive (getting the most out of what you have available) rather than something negative (worrying about never having enough time). Furthermore, well-designed limitations can actually improve your performance.
Of course, there are disadvantages as well. Embracing constraints means accepting that you are operating at less than your full potential. Yes, there are plenty of ways to “work smarter, not harder” but it is difficult to avoid the fact that where you spend your time matters. If you invested more time into your health or your relationships or your career, you would likely see improved results in that area.
A third way to manage your four burners is by breaking your life into seasons. What if, instead of searching for perfect work-life balance at all times, you divided your life into seasons that focused on a particular area?
The importance of your burners may change throughout life. When you are in your 20s or 30s and you don’t have children, it can be easier to get to the gym and chase career ambitions. The health and work burners are on full blast. A few years later, you might start a family and suddenly the health burner dips down to a slow simmer while your family burner gets more gas. Another decade passes and you might revive relationships with old friends or pursue that business idea you had been putting off.
You don’t have to give up on your dreams forever, but life rarely allows you to keep all four burners going at once. Maybe you need to let go of something for this season. You can do it all in a lifetime, but not at the same damn time. In the words of Nathan Barry, “Commit to your goal with everything you have—for a season.”
For the last five years, I have been in my entrepreneurship season. I built a successful business, but it came with costs. I turned my friends burner way down and my family burner is only running halfway.
What season are you in right now?
The Four Burners Theory reveals an inconsistency everyone must deal with: nobody likes being told they can’t have it all, but everyone has constraints on their time and energy. Every choice has a cost.
Which burners have you cut off?
By: James Clear
These are the top 5 things that could possibly kill your iPhone.
In my days of being on team iPhone I’ve definitely dealt with a few of these factors.
Share this message to raise awareness of ways to lengthen the life of iPhones to other users and potential users. You just never know who will view this message and be massively impacted by it.
The new tax deal has given the $2,500 a year American Opportunity Tax Credit (AOTC) permanent life instead of expiring at the end of 2017. The credit reduces your federal tax bill dollar-for-dollar by up to $2,500 per year for each eligible college student for whom you pay qualified tuition expenses. It can be claimed on behalf of an undergraduate for four years—that’s a $10,000 tax subsidy, over four years. And if you have more than one child in college at the same time, you can claim more than one credit.
This break had been set to expire at the end of 2017, after the fiscal cliff deal extended it for tax years 2013-2017. The new (December 2015) tax deal makes the credit permanently available, and that is good news for parents trying to pay for the high cost of college. The tax deal also made computers, iPads and tablets a qualified expense under 529 college savings plan rules.
The American Opportunity Tax Credit is worth more than the older college-related tax credits you might have heard of: the Hope Scholarship and Lifetime Learning Credits. It’s also more valuable than another tax break, the tuition and fees deduction. But understandably, having all of those credits creates a lot of confused taxpayers and leads some to miss out.
This is my tribute to ‘The Greatest’ Muhammad Ali. He was absolutely a beast in the ring. See for yourself below. Really?! 21 Punches dodged in 10 seconds. Ridiculous!