Alopecia With Endocrine Therapies in Patients With Cancer.


Abstract

Background. Whereas the frequency of alopecia to cytotoxic chemotherapies has been well described, the incidence of alopecia during endocrine therapies (i.e., anti-estrogens, aromatase inhibitors) has not been investigated. Endocrine agents are widely used in the treatment and prevention of many solid tumors, principally those of the breast and prostate. Adherence to these therapies is suboptimal, in part because of toxicities. We performed a systematic analysis of the literature to ascertain the incidence and risk for alopecia in patients receiving endocrine therapies.

Methods. An independent search of citations was conducted using the PubMed database for all literature as of February 2013. Phase II–III studies using the terms “tamoxifen,” “toremifene,” “raloxifene,” “anastrozole,” “letrozole,” “exemestane,” “fulvestrant,” “leuprolide,” “flutamide,” “bicalutamide,” “nilutamide,” “fluoxymesterone,” “estradiol,” “octreotide,” “megestrol,” “medroxyprogesterone acetate,” “enzalutamide,” and “abiraterone” were searched.

Results. Data from 19,430 patients in 35 clinical trials were available for analysis. Of these, 13,415 patients had received endocrine treatments and 6,015 patients served as controls. The incidence of all-grade alopecia ranged from 0% to 25%, with an overall incidence of 4.4% (95% confidence interval: 3.3%–5.9%). The highest incidence of all-grade alopecia was observed in patients treated with tamoxifen in a phase II trial (25.4%); similarly, the overall incidence of grade 2 alopecia by meta-analysis was highest with tamoxifen (6.4%). The overall relative risk of alopecia in comparison with placebo was 12.88 (p < .001), with selective estrogen receptor modulators having the highest risk.

Conclusion. Alopecia is a common yet underreported adverse event of endocrine-based cancer therapies. Their long-term use heightens the importance of this condition on patients’ quality of life. These findings are critical for pretherapy counseling, the identification of risk factors, and the development of interventions that could enhance adherence and mitigate this psychosocially difficult event.

 

Source: The Oncologist.

 

 

Man In India Who Claims That He Has Not Eaten or Drunk Any Liquid In 70 Years Examined By Scientists | MyScienceAcademy


Doctors and experts are baffled by an Indian man who claims not to have eaten or drunk anything for 70 years – but is still in perfect health.

A team of scientists and doctors in Sterling Hospital, in the western Indian city of Ahmedabad, are studying the claims of Prahlad Jani, a local holy man, who is over 70 years old.

He claims to have been blessed by a goddess when he was 8-years-old, which has enabled him to survive without sustenance and that he derives energy through meditation.

Most people can live without food for several weeks, with the body drawing on its fat and protein stores. But the average human can survive for only three to four days without water.

watch the small video clip.

URL: http://www.youtube.com/watch?v=FGF7EY2Ucm8

Sugar Substitutes—What’s Safe and What’s Not.


Story at-a-glance

  • Sugar substitutes can be divided into four general categories: artificial sweetener, sugar alcohols, natural sweeteners, and dietary supplements such as Stevia and Lo Han
  • Artificial sweeteners can actually be far worse for you than sugar and fructose, and scientific evidence backs up that conclusion
  • Furthermore, numerous studies show they increase weight gain and worsen insulin sensitivity to a greater degree than sugar
  • Natural sweeteners such as honey and agave may seem like a healthier choice, but not only are they loaded with fructose, many are also highly processed
  • In moderation, some sugar alcohols can be a better choice than highly refined sugar, fructose or artificial sweeteners. Of the various sugar alcohols, xylitol is one of the best. When it is pure, the potential side effects are minimal
  • Three of the best sugar substitutes are all-natural Stevia from the whole plant, Lo Han Guo, and dextrose (pure glucose). Contrary to fructose, glucose can be used directly by every cell in your body and as such is a far safer sugar alternative.

Artificial Sweetener

With all the dire health effects associated with refined sugar and high fructose corn syrup (HFCS), many wonder what, if anything, is actually safe to use to sweeten your foods and beverages.

It’s certainly a good question. You do have to be cautious when choosing an alternative, as many sweeteners that are widely regarded as “healthy” are, in reality, anything but. A previous National Geographic article1 set out to compare eight different sugar substitutes, which fall into four general categories:

  • Artificial sweeteners
  • Sugar alcohols
  • Natural sweeteners
  • Dietary supplements

Sadly lacking from their review are any notations about adverse health effects of many of the sugar substitutes tested.

Despite copious scientific evidence of harm, artificial sweeteners, for example, are promoted in the featured article, and by “experts” in general, as safe because they “pass through your body undigested.” Needless to say, safety concerns will be front and center in this article.

The Case Against Artificial Sweeteners

Sweetener lesson 101: Avoid artificial sweeteners like the plague. While the mechanisms of harm may differ, they’re all harmful in one way or another. This includes aspartame (NutraSweet, Equal), sucralose (Splenda), saccharin(Sweet’N Low), acesulfame potassium, neotame, and others.

Twenty years ago I wasn’t sure, but now there’s little doubt in my mind  that artificial sweeteners can be far worse for you than sugar and fructose, and there is plenty of scientific evidence to back up that conclusion. In fact, there’s enough evidence showing the dangers of consuming artificial sweeteners to fill an entire book — which is exactly why I wrote Sweet Deception.

Aspartame is perhaps the most dangerous of the bunch. At least it’s one of the most widely used and has the most reports of adverse effects. There are also hundreds of scientific studies demonstrating its harmful effects.

This is why it’s so frustrating to see big companies like Coca-Cola Company purposely deceive you on this issue, which is exactly what they’re currently doing with their “public service” announcement-type ads, in which they “affirm” aspartame’s safety and benefits.

Center for Science in the Public Interest’s (CSPI) Executive Director Michael F. Jacobson issued the following statement in response to Coca-Cola’s new ad:2

“Aspartame has been found to cause cancer3leukemia, lymphoma, and other tumors—in laboratory animals, and it shouldn’t be in the food supply. We certainly want Coca-Cola to shift its product mix toward lower- and no-calorie drinks, but aspartame’s reputation isn’t worth rehabilitating with this propaganda campaign.

The company would be better off phasing out its use of aspartame and accelerating its research into safer, natural sweeteners such as those extracted from the stevia plant.”

Don’t Fall for Coca-Cola’s Deceptive “Public Announcement” Ads

Besides pulling the wool over your eyes with regards to the lack of overall safety of aspartame, I think the FTC would be warranted to sue Coke and the other diet soda manufacturers for fraudulent advertising, seeing how:

    1. There’s no scientific evidence showing that the use of diet sodas actually lead to weight loss.

On the contrary, studies have repeatedly shown that artificial sweeteners cause greater weight gain than regular sugar.4 Studies have also repeatedly linked artificial sweeteners with increased hunger. For example, one study published in the journal Physiology & Behavior in 19885 found that intense (no- or low-calorie) sweeteners can produce significant changes in appetite. Of the three sweeteners tested, aspartame produced the most pronounced effects.

    1. Scientific evidence shows that aspartame actually worsens insulin sensitivity to a greater degree than sugar.

This is quite the blow for diabetics who obediently follow the recommendation to switch to diet sodas to manage their condition. Unfortunately, in large part due to misleading and deceptive advertising, many doctors and registered nutritionists are still under the illusion that artificial sweeteners are a safe and effective alternative for their diabetic patients.

Artificial sweeteners also appear to cause many of the same health effects associated with high sugar consumption.  Most recently, a report published in the journal Trends in Endocrinology & Metabolism6 highlighted the fact that diet soda drinkers suffer the same exact health problems as those who opt for regular soda, including excessive weight gain, type 2 diabetes, cardiovascular disease and stroke.7, 8 According to the authors:

“This paper… considers the hypothesis that consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned responses that normally contribute to glucose and energy homeostasis. Because of this interference, frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing metabolic derangements.”

So the very reason anyone would consider using diet instead of sugared sweeteners has no basis in fact. Anyone using them would get the same problems as using regular sugar and expose themselves to the well documented risks of artificial sweeteners.

Be Critical of “All Natural” Sweetener Claims

With artificial sweeteners are out of the picture, let’s look at some all-natural sweeteners. Natural sweeteners such as honey and agave may seem like a healthier choice, but not only are they loaded with fructose, many are also highly processed. In that regard, you’re not gaining a thing. The health effects will be the same, since it’s the fructose that causes the harm.

Agave syrup can even be considered worse than HFCS because it has a higher fructose content than any commercial sweetener, ranging from 70 to 97 percent depending on the brand. HFCS, in comparison, averages 55 percent fructose. What’s worse, most agave “nectar” or agave “syrup” is nothing more than a laboratory-generated super-condensed fructose syrup, devoid of virtually all nutrient value.

Honey is also high in fructose, averaging around 53 percent, but contrary to agave it is completely natural in its raw form,and has many health benefits when used in moderation. Keep in mind you’re not likely to find high quality raw honey in your local grocery store. Most of the commercial Grade A honey is highly processed and of poor quality. All in all, it’s important to realize that regardless of the source (be it HFCS, honey or agave), refined fructose:

  • Tricks your body into gaining weight by fooling your metabolism, as it turns off your body’s appetite-control system. Fructose does not appropriately stimulate insulin, which in turn does not suppress ghrelin (the “hunger hormone”) and doesn’t stimulate leptin (the “satiety hormone”), which together result in your eating more and developing insulin resistance.
  • Activates a key enzyme that causes cells to store fat; this is the so-called “fat switch” revealed in Dr. Richard Johnson’s book by the same name.
  • Rapidly leads to weight gain and abdominal obesity (“beer belly”), decreased HDL, increased LDL, elevated triglycerides, elevated blood sugar, and high blood pressure—i.e., classic metabolic syndrome.
  • Is broken down in your liver just like alcohol, and produces many of the side effects of chronic alcohol use, including non-alcoholic fatty liver disease (NAFLD). Interestingly enough, research has shown that soft drinks increase your risk of NAFLD independently of metabolic syndrome9.
  • Over time leads to insulin resistance, which is not only an underlying factor of type 2 diabetes and heart disease, but also many cancers.

What About Sugar Alcohols?

Sugar alcohols can be identified by the commonality of “ol” at the end of their name, such as xylitol glucitol, sorbitol, maltitol, mannitol, glycerol, and lactitol. They’re not as sweet as sugar, and they do contain fewer calories, but they’re not calorie-free. So don’t get confused by the “sugar-free” label on foods containing these sweeteners. As with all foods, you need to carefully read the food labels for calorie and carbohydrate content, regardless of any claims that the food is sugar-free or low-sugar.

One reason that sugar alcohols provide fewer calories than sugar is because they’re not completely absorbed into your body. Because of this, eating too many foods containing sugar alcohols can lead to abdominal gas and diarrhea. It’s also worth noting that maltitol, a commonly used sugar alcohol, spikes blood sugar almost as much as a starchy new potato. Xylitol, in comparison, does not have a great effect on your blood sugar, so from that perspective may be a better choice.

So, in moderation, some sugar alcohols can be a better choice than highly refined sugar, fructose or artificial sweeteners. Of the various sugar alcohols, xylitol is one of the best. When it is pure, the potential side effects are minimal, and it actually comes with some benefits such as fighting tooth decay. All in all, I would say that xylitol is reasonably safe, and potentially even a mildly beneficial sweetener. (As a side note, xylitol is toxic to dogs and some other animals, so be sure to keep it out of reach of your family pets.)

Three of the Safest Sugar-Alternatives

Two of the best sugar substitutes are from the plant kingdom: Stevia and Lo Han Guo (also spelled Luo Han Kuo). Stevia, a highly sweet herb derived from the leaf of the South American stevia plant, is sold as a supplement. It’s completely safe in its natural form and can be used to sweeten most dishes and drinks.

Keep in mind that the same cannot be said for the sugar substitute Truvia, which makes use of only certain active ingredients and not the entire plant. Rebaudioside A is the agent that provides most of the sweet taste of the plant. Usually it’s the synergistic effect of all the agents in the plant that provide the overall health effect, which oftentimes includes “built-in protection” against potentially damaging effects, but what the FDA has approved as GRAS (generally recognized as safe) are just a couple of the active ingredients, including rebaudioside A used in Truvia.

In one toxicology review,10 the researchers point out that stevioside compounds and rebaudioside A are metabolized at different rates, making it impossible to assess the risk of rebaudioside A from toxicity assessments of stevioside (which has been used as food and medicine in Japan and South America for decades or longer). Additionally, in a human metabolism study, stevioside and rebaudioside A had different pharmacokinetic results. In layman’s terms, that means that your body reacts differently to the two compounds; each compound is metabolized differently and remains in your body for different lengths of time.

Truvia may turn out to be a very good substitute to sugar, but I’d have to see more details before giving it an enthusiastic thumbs-up – for the same reason the FDA uses as the basis for their refusal to consider Stevia GRAS: there’s just not enough evidence to prove its safety. Lo Han Kuo is another natural sweetener similar to Stevia, but it’s a bit more expensive and harder to find. In China, the Lo Han fruit has been used as a sweetener for centuries, and it’s about 200 times sweeter than sugar. It received FDA GRAS status in 2009.

A third alternative is to use pure glucose. You can buy pure glucose (dextrose) for about $5-7 per pound. It is only 70 percent as sweet as sucrose, so you’ll end up using a bit more of it for the same amount of sweetness, making it slightly more expensive than regular sugar—but still well worth it for your health as it does not contain any fructose whatsoever. Contrary to fructose, glucose can be used directly by every cell in your body and as such is a far safer sugar alternative.

Consider Dampening Your Sweet-Tooth…

Keep in mind though that if you have insulin issues, high blood pressure, high cholesterol, diabetes, or if you’re overweight, you’d be best to avoid all sweeteners, including Stevia, Lo Han and dextrose, since any sweetener can decrease your insulin sensitivity. (Most important of all, remember that this goes for artificial sweeteners too!) If you’re having trouble weaning yourself off sweet foods and beverages, try Turbo Tapping. It’s a clever use of the Emotional Freedom Techniques (EFT), specifically designed to resolve many aspects of an addiction in a concentrated period of time.

Tell Coke They’re a Joke!

Obesity and related metabolic diseases are serious public health problems in the United States, and you are being sorely misled by companies pretending to have a solution that, in reality, only worsen the problem. I strongly urge you to let the Coca-Cola Company know how you feel by telling them to stop their deceptive marketing of soda products. Especially their fake “public announcement” ads for aspartame.

Secrets of Effective Office Humor.


Making colleagues laugh takes timing, self-confidence—and the ability to rebound from a blooper.

Margot Carmichael Lester loves making good-natured jokes at work. As owner of The Word Factory, a Carrboro, N.C., content-creation company, she looks for employees with a sense of humor. “I only want to work with people who can take a joke.”

Sometimes, though, her jokes fall flat. Last month, at a meeting with insurance-industry clients, she poked fun—gently—at how people often view their insurers: “I mean, who really expects to hear, ‘I’m calling from your insurance company and I’m here to help?’ ” The joke died amid a few titters, she says. While she recovered and completed the client project successfully, the memory lingers. “If you are funny and putting yourself out there, making yourself vulnerable, and people don’t respond? That hurts.”

Employers like to hire people with a sense of humor, research shows. And mixing laughter and fun into a company culture can attract skilled workers, according to a study last year in the journal Human Relations. A 2011 study at Pennsylvania State University found that a good laugh activates the same regions of the brain that light up over a fat bonus check.

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But the office can be a comedic minefield. Making colleagues laugh takes timing, self-confidence—and the ability to rebound from a blooper.

“People will like you better if they find you funny. They will also think you are smarter,” says Scott Adams, creator of the popular syndicated cartoon “Dilbert.” But “if you’ve never been funny before, trying to start in the workplace—the most important place you’ll ever be in your life”—is a terrible idea, says Mr. Adams, author of a new book, “How to Fail at Almost Everything and Still Win Big.”

Fred Kilbourne says his knack for funny banter has helped his career as an actuary, making him a sought-after speaker and participant in professional groups. “Actuarial work can be pretty dull and deadly, and I’m always looking for a way to make it a little lighter,” says Mr. Kilbourne, of San Diego. “People say, ‘I can’t tell when you’re kidding.’ My usual answer is, ‘If my lips are moving, I’m kidding.’ “

Not that he hasn’t had a few missteps. He once cracked a joke in the middle of a serious discussion by a committee on auto-insurance risk, prompting a fellow participant to say, ” ‘You know, we’re trying to get something serious done here, and this is not helpful,’ ” recalls Mr. Kilbourne. “He was right,” he says. “I was a serious contributor for the rest of the meeting.”

Office jokesters must be ready with a funny comeback if they drop a clunker, making sure to deliver it in a warm, non-sarcastic tone, says Michael Kerr, a Calgary, Alberta, speaker, author and consultant on humor at work. Turn the joke on yourself. For example: “It takes a special human being to do what I just did,” or, “This is great. I was feeling a little under-stressed today,” Mr. Kerr says.

It is also important to read the nuances of co-workers’ moods and attitudes and pick the right context for jokes, says Andrew Tarvin, a New York City humor coach. Mr. Adams says he watches listeners’ body language. If they tense up, or they avert their gaze or narrow their eyes, it isn’t a good time to crack wise.

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Most people know the taboos: Divisive racist, ethnic or sexist jokes, are out. Beyond those boundaries, a jokester should consider the ramifications if a joke showed up on Twitter or Facebook.

One way to keep humor positive is to apply the “yes–and” technique used in improvisational comedy, says Zach Ward, managing director of ImprovBoston, a Cambridge, Mass., theater and humor-training school. (Many students come there, he says, to build interpersonal skills they can use in the workplace.) A co-worker who hears a joke might “actively add to what you have you have said,” he says. If the sound system crashes during a presentation, for example, the speaker might say, “Was it something I said?” while other employees might play off and extend the witticism with, “It must have been your electrifying humor,” or “Whose turn was it to pay the electrical bill?”

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The best office humor brings people together, often through shared pranks or inside jokes, Mr. Tarvin says. For nearly three years, employees at Silver Lining Ltd. held monthly “corporate jargon days” when they tried to use as much vague, bureaucratic language as possible, says Carissa Reiniger, founder and chief executive of the New York City-based small-business management consulting firm.

A study published earlier this year in the Leadership & Organization Development Journal says executives and managers who use self-deprecating humor appear more approachable and human to subordinates.

Paul Spiegelman, co-founder of BerylHealth, a Bedford, Texas, medical call-center company, stars in annual office videos. One year, he was shown applying for jobs as a short-order cook and a theater projectionist because he didn’t “feel valued any more at the company.” Another year, in a parody of “Dancing with the Stars,” he donned in-line skates and a matador costume and danced with his chief operating officer.

Humor “breaks down silos and flattens the organization,” fostering employee loyalty and productivity, says Mr. Spiegelman, who recently sold the company to SteriCycle Inc., where he is chief culture officer.

Any employee, however, can use “self-enhancing” humor to make light of failures, polish her image or rise above stress, Dr. Cruthirds says. One study cited a team of co-workers who kidded each other almost constantly. In a meeting where one employee delivered a document with a mistake in it, a laughing co-worker accused him of failing his word-processing training. The perp’s comeback drew another laugh: “I find it really hard to be perfect at everything.”

Beth Slazak’s part-time job in a physician’s office requires taking calls about medical records from people who are often tense and rushed. To lighten things up, Ms. Slazak, of Cowlesville, N.Y., answers the phone with fictitious job titles. Her first one, “This is Beth, Office Ray of Sunshine,” made a co-worker sitting nearby spit out her coffee, Ms. Slazak says. Others include Dragon Slayer, Narnia Tour Guide, Zombie Defender and Hope for All Mankind.

Her boss and co-workers in the small office approve, she says, since they’re not the only ones who laugh: Callers almost always do, too. “If you can get somebody who sounds uptight to giggle, it’s totally a win,” says Ms. Slazak.

Source: WSJ.

Money Isn’t a Dirty Word: How to Use Money to Serve Your Purpose.


“What we really want to do is what we are really meant to do. When we do what we are meant to do, money comes to us, doors open for us, we feel useful, and the work we do feels like play to us.” ~ Julia Cameron

So many of us cringe at the image of a person who loves money. We tend to think it’s tacky, greedy, and not noble to strive to be rich. And for those of us who want to do work that serves the world in a positive way, money can start to feel like a dirty word.

how-to

And I’m here to change that.

I don’t believe money is the root of all evil. Nor do I believe money can buy happiness. But I do believe that when we can get rid of our hang-ups around money, it allows us to serve the world in a bigger way. Especially if your career is centered around doing good in the world, it’s important for you to embrace making money as a part of your making-a-difference strategy.

It’s time to stop shaming yourself for wanting to make money in your career or your passion-based business. You might think it’s noble to work for free or low cost and help the less fortunate, but there is nothing noble about not being able to pay your rent.

In order to do good in the world, you must be able to take care of yourself first. And when you do that, you stop playing small and you can fully step into what you were put here to do – fulfill your purpose through your work.

Here’s how you can start shifting your money mindset right now:

1. Acknowledge that what you do has value

And even more than that, acknowledge that who you are has value. All of us have our own unique gifts that we don’t think are that remarkable, when in fact, these are the very traits that others admire in us. The more you can play up who you are at your core, the more you will see the value that you bring to the world around you. And the more value you can find in your own self worth, just the way you are, the easier it is to see why people would pay you for these qualities. You are different and special, and you deserve to be paid well for doing that special thing that only you can do.

2. Start to love money

Like, really love it. Part of this practice is being grateful for all the things that money helps you do in your life. With money, you can buy yourself healthy organic food, you can support your local charities, you can give your kids an education. When you start to realize how the money you make is able to be filtered back into your life s a source of growth, you start to become grateful for every penny you earn, because you know it allows you to give back to yourself and your community.

3. Stop discounting money as something you don’t need

Stop discounting money as something you don’t need, and imagine a life where money flows freely. Recognize that you DO need money to live, and pay attention to how it would feel to no longer have to be penny pinching, or budgeting carefully every month. Imagine a life where you had all the money you wanted, more than you knew what to do with. How would you spend it? What would you do with it? Imagine the possibilities of how you could use that extra money as a force for good in the world, how many lives you could shape with it, how many of the world’s problems you could solve by re-investing it back into your community.  Start thinking of money as possibility instead of burden, and notice how much energy that brings to your purpose in the world. Money could help you build that school in Africa, or support your local animal shelter, or run the women’s group you volunteer at. Money is essential in helping support your purpose and passions.

When you stop fearing money and start allowing yourself to fall in love with it, doors open for you like you might never have imagined. Making money is not a sin and wanting money is not a sin. Money gives you the gift of taking care of yourself and those around you, which allows you to live a life that lets you help the world in a bigger way.

Money can be used as a force of good in the world. You just have to let it in.

Do you believe money is the root of all evil? What are some of the limiting beliefs you borrowed from others when it comes to money? Share your insights by joining the conversation in the comment section bellow.

Source:Purpose fairy

Rattling ions limit heat flow in materials used to reduce carbon emissions.


A new study published today in the journal Nature Materialss has found a way to suppress the thermal conductivity in sodium cobaltate so that it can be used to harvest waste energy.

Led by scientists at Royal Holloway University, the team conducted a series of experiments on crystals of sodium cobaltate grown in the University’s Department of Physics. X-ray and neutron scattering experiments were carried out at the European Synchrotron Radiation Facility and in the Institut Laue-Langevin in Grenoble, using the UK’s national supercomputer facility HECToR to make their calculations.

They believe their approach can easily be applied to other substances, since they only require tiny crystals and will, therefore, guide the design of the next generation of thermoelectric materials.

“The global target to reduce carbon emissions has brought research into thermoelectric materials centre stage,” said Professor Jon Goff from the Department of Physics at Royal Holloway.

“If we can design better thermoelectric materials, we will be able to reduce the energy consumption of cars by converting waste heat in exhausts into electrical power, as well as cooling hot spots on computer chips using solid state refrigerators.”

Thermoelectric coolers are also used in air conditioners and in scientific equipment where a rapid response to changes in temperature is required. Energy harvesting is also important in miniaturised electronic devices, including “systems on a chip“, and power recovery using this method is useful for any off-grid electricity applications, including in space.

“The development of thermoelectric oxides offers an environmentally clean alternative to current materials that contain elements that are harmful, such as lead, bismuth or antimony, or those that are in limited supply, such as tellurium,” added Professor Goff.

Source: http://phys.org

10 Steps to Create What Your Desire.


Want to Change Something in Your Life? If so, here are 10 Steps to Create What Your Desire:

1. Name that which you want but do not have

This first step actually requires some new awareness, as what you want may be combobbled up with a mess of thinking that now rests in “I’m not happy or satisfied.” So pause, take a breath, and let rise to the surface new clarity about what you are missing and now want.

2. Consider this: is what you want solely about you, or might it benefit others as well?

In my view, corporations that focus on profit, rather than on a bigger mission or service, are missing the boat. Those corporations typically operate in a low-trust culture that limits innovation and inspired action. Conversely, corporations that have a service or products to offer that benefit others, and work toward that vision, profit is acquired naturally. Same is true for people. If you find yourself solely on the “me plan” (as Sakyong Mipham says), you may be limiting yourself in achieving bigger outcomes that serve both you and others.

3. Your “because” statement

Answer: “Why don’t you have it?” Your “because” statement probably points you to an old mind set (thought-belief-habit) that is keeping you from having what you want.

Good to write out your “because” statement and not just think about it. Once you get it on paper you will automatically gain the awareness of what has been stopping you that may seem real, but actually is not true. Check out the actual facts, and take care of what’s physically missing that you have control over, like needed training or experience. If you have the necessary resources, then a good deal of what’s keeping you from what you want is locked in an unconscious limiting belief and needs to be unearthed and reinvented.

4. Name a new condition that you want present in your life.

Saying “a million dollars” is not useful, because it won’t come flying in the window. But rather than being practical, be thoughtfully specific. Delve into the possibilities, and come up with what calls to you. If you think it is about money, first ask yourself how a certain amount of money would actually make a difference. If you answer, “an updated or new car model”, hold the vision on that car instead of a dollar amount.  If you really want to target a money amount, identify the specific target outcome you desire and are committed to.  For example, “more money” won’t work; but “add $20,000 to my bank account in the next five years,” does work. (Then you might brainstorm how you can add to your current income flow or cost reductions to achieve your goal.)

5. Visualize the outcome as present, now.

Experience how achieving your intention feels. See it visually accomplished. Think how the achievement will benefit you. Relish in your success. Give yourself a ‘high five’ and say out loud: “Yes!” (Fist pump appropriate!)

6. Adopt a new mindset that affirms the reality you desire.

Best to start with “I am . . . (fill in the blank) and lovingly repeat this affirmation throughout the days ahead. Again, in addition to saying it, see it completed, and how great it feels!

7. Listen to your inner guide (intuition) for inspired ideas.

Jump on any insights and quickly take action. Do whatever you can to move closer to your target achievement. I find that sitting quietly and asking a pertinent question if most often followed by a thought/answer “popping” in my mind. Acting on intuitive hunches can open up new possibilities. Keep going~ committed persistence is powerful!

8. Track and acknowledge small gains you are making.

More fist pumps are very good! Any small celebration actually creates greater inner confidence, which in turn leads to additional risk-taking and more powerful outcomes.

9. If you notice you are on the wrong track, immediately take a “come-back” action such as:

Sometimes you just need to break through some resistance, or add-in a fresh affirmation that inspires action. Reinvent a way back or ahead, and keep going.

Check out new resources you made need, including education, training, or coaching assistance. Having a trusted partner is hugely important.

Modify your approach based on new information coming your way. (The analogy of an airplane being off course most of the time on its way to the destination applies; because the pilot keeps making small course corrections, the flight arrives at its destination pretty much on time.)

10.  Arrive at your target destination

Arrive at your target destination, (or next step on your path), pat yourself on the back, and appropriately celebrate big time! (Fist pumps are now mandatory!)

Source: http://www.purposefairy.com

 

Making Clinical Trials More Efficient, Informative, and Effective


recent op-ed in the New York Times by journalist and cancer advocate Clifton Leaf asked the question, do clinical trials work? The answer is a straightforward yes. A clinical trial is a tool that when correctly employed can identify more-effective treatments for patients with cancer and other diseases.

It is important to acknowledge that some clinical trials have not been as informative as we would like. Some have shown “improvements” that might not be considered groundbreaking. But others have truly changed the standard of care for a given disease in a single day.

The questions today are, how do we increase the number of informative trials that can change practice and save lives? How do we evaluate promising therapies in the shortest possible time? And when do we stop and move on when the results are not as positive as expected? A well-designed clinical trial can accomplish these goals.

My colleagues and I are focusing on streamlining our clinical research program, which will allow more patients to participate in more trials, and also bring novel compounds and therapies to those who can benefit from them in a timely manner. At Memorial Sloan-Kettering, patients and researchers are typically involved in more than 900 total clinical trials at any given time.

The Traditional Paradigm

The standard approaches for developing most cancer treatments have been built on a rigid sequence of clinical trials. Historically these studies advanced the field slowly over time with incremental improvements. Each step reset the benchmark to which subsequent treatments were compared. This approach served us for many years as standard chemotherapy agents with broad applicability across many patients and diseases were being developed.

The development of agents such as cisplatin, carboplatin, and paclitaxel all occurred in this way and these agents still form the backbone of many cancer treatments.

The traditional paradigm of evaluating agents required them to move through phase I, II, and III trials, often over a protracted period of time. The phase I trial was intended to establish a dose — the “maximum tolerated dose” — and to establish safety. These phase I trials were generally small, and an assessment of the effectiveness of the agent was usually not the goal.

The next step involved a phase II trial classically with 35 or so patients enrolled to see if a certain group of patients would have tumor shrinkage and for what period of time. We often accepted a rather low number of patients showing improvement as evidence of activity.

If results of the phase II trial were positive, the investigation would move to randomized phase III trials with large numbers of patients, known in clinical trials as cohorts. Large numbers are required to detect a difference between a new and old treatment, particularly if the differences are expected to be small. Phase III trials often are done at many medical centers around the nation, and sometimes around the world, making orchestration complex, and the time required to get results can be long.

Rethinking the Large Trial

Just as the computing tools we used five years ago would seem completely inadequate to support us now, the rigid clinical trial paradigm described above has also become outmoded in many situations. Clinical trials remain the best way to improve cancer treatments, but what we need to rethink and avoid is the large clinical trial with long follow-up looking for very small improvements. (Several examples were discussed in the op-ed by Mr. Leaf.)

In particular, this approach will not serve us well in the era of mechanism-based or targeted therapies in which the therapy being tested may only work in a small group of patients but may be highly effective in that group.

The idea of aligning patients who carry a specific therapeutic target with a specific drug has resulted in higher response rates than have been previously seen, and now combination therapy is being considered to overcome the resistance that tumors often develop to anticancer drugs. New cancer drugs are initially tested in phase I trials, but we have become more nimble in confirming these responses early on rather than moving down the traditional paradigm.

The Basket Trial

The development of the “basket” trial is one example. Instead of starting with multiple clinical trials in different diseases (which requires duplication of regulatory and infrastructure efforts), we start with one trial — the basket — and one or more targets, and allow patients with multiple diseases to enroll in cohorts or groups.

If one group shows good response, we expand this group to immediately assess whether others could benefit from the new therapy. If another group is unfortunately not showing evidence of effectiveness, this group may be closed and the patients can move on to consider other therapy. In this way, the exploration of the effectiveness of a treatment occurs early, quickly, and in one trial.

The optimal phase I trial today often explores drugs with innovative mechanisms. When a robust response rate is seen and the group is expanded sufficiently (called an expansion cohort), this can sometimes bring enough confidence of effectiveness in the phase I trial that smaller randomized trials can be immediately done to confirm the findings.

For example, a recent Memorial Sloan-Kettering study of nivolumab and ipilimumab in patients with advanced melanoma, conducted by medical oncologist Jedd Wolchok and colleagues, was expanded so that 53 patients received the combination therapy in the initial trial. In this study, 53 percent of patients had significant reduction in tumor size by 80 percent or more. This trial rapidly confirmed the activity of this combination without having to go to a traditional phase II trial.

Smaller, Smarter Trials

There are two ways to increase the likelihood that a new treatment shows benefit in contemporary clinical trials. The first is to align the right patient with the right target in trials of therapeutic agents that target a specific mutation or pathway. The second is to identify biomarkers for response — for example, an abnormality measurable in the blood or detectable in the tumor specimen that when present can predict response to a particular agent — as a critical part of new drug development. In this way, we can give a new treatment to those people who are most likely to benefit.

We also need to continue to develop new statistical designs. One of these is called the Bayesian approach, where treatment arms in a given trial are frequently reviewed. The ones that are better performing will enroll more patients, and those doing less well get closed as soon as possible.

We are essentially moving toward smaller and smarter trials looking for clearly meaningful improvements. This allows us to evaluate strategies faster and, most importantly, increase the chance of benefit for individual patients.

When a clinical trial is well designed — whether the results are positive or negative — we learn important next steps. In addition, if we can match the right patient to the right trial, the number of successful approaches will continue to rise.

The clinical trial remains our best tool to identify new therapies, but as with all tools, innovation is required if trials are to remain relevant. We have more novel agents and approaches to consider than ever before, and well-designed clinical trials remain the best way forward.

Source: http://www.mskcc.org

 

Common fruit provide a dietary source of melatonin.



Abstract Title:

Dietary Intake of Melatonin from Tropical Fruit Altered Urinary Excretion of 6-Sulfatoxymelatonin in Healthy Volunteers.

Abstract:

This study assessed the melatonin content of six tropical fruits and examined whether human consumption could contribute to dietary melatonin as measured by 6-sulfatoxymelatonin (aMT6-s, a marker of circulating melatonin in the body). Melatonin was extracted using methanol and analyzed by high-performance liquid chromatography. In a clinical crossover study, 30 healthy volunteers consumed selected fruits one at a time, with a 1week wash-out period between fruits, until completing all six fruits. Most fruits had moderate melatonin content. Significant increases in urine aMT6-s concentrations were seen after the consumption of pineapple (266%, p = 0.004), banana (180%, p = 0.001), and orange (47%, p = 0.007). The need to analyze melatonin both in fruit and as in vivo uptake was demonstrated. Further study is warranted regarding the clinical effect of fruit consumption in people with age-related melatonin reduction problems such as sleeplessness and illnesses involving oxidative damage.

Source: http://www.greenmedinfo.com