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Microneedles help target therapeutics to the back of the eye

Thanks to tiny microneedles, eye doctors may soon have a better way to treat diseases such as macular degeneration that affect tissues in the back of the eye. That could be important as the population ages and develops more eye-related illnesses—and as pharmaceutical companies develop new drugs that otherwise could only be administered by injecting into the eye with a hypodermic needle.

For the first time, researchers from the Georgia Institute of Technology and Emory University have demonstrated that microneedles less than a millimeter in length can deliver drug molecules and particles to the eye in an animal model. The injection targeted the suprachoroidal space of the eye, which provides a natural passageway for drug injected across the white part (sclera) of the eye to flow along the eye’s inner surface and subsequently into the back of the eye. The minimally invasive technique could represent a significant improvement over conventional methods that inject drugs into the center of the eye—or use eyedrops, which have limited effectiveness in treating many diseases.

The study was reported in Investigative Ophthalmology & Visual Science. The research was supported by the National Eye Institute, which is part of the National Institutes of Health, and by the organization Research to Prevent Blindness.

“This research could lead to a simple and safe procedure that offers doctors a better way to target drugs to specific locations in the eye,” said Samirkumar Patel, the paper’s first author and a postdoctoral researcher at Georgia Tech when the research was conducted. “The design and simplicity of the microneedle device may make it more likely to be used in the clinic as a way to administer drug formulations into the suprachoroidal space that surrounds the eye.”

Patel, who is now director of research for Clearside Biomedical—a startup company formed to commercialize the technology—said the study also showed that the suprachoroidal space could accommodate a variety of drugs and microparticles. That could open the door for the use of timed-release drugs that could reduce the need for frequent injections to treat chronic eye diseases.

The suprachoroidal space is located between two important structures in the eye: the sclera and the choroid. Fluids injected into that space travel circumferentially around the eye, which flows drug solution directly over the choroid and adjacent retina—which are the targets for many drug compounds. The new study showed that injections of fluids containing molecules and particles into that space not only reach the targeted structures, but also remain there for extended time periods. And equally important, the molecules and particles do not significantly reach the lens or front part of the eye, where side effects from drugs can occur.

“The study showed that if we inject non-degradable particles into the suprachoroidal space and wait as long as two months, the particles remain,” said Mark Prausnitz, a Regents professor in Georgia Tech’s School of Chemical and Biomolecular Engineering. “That means there is no natural mechanism to remove the particles from the eye. Knowing this, we can design biodegradable particles with drugs encapsulated in them that can slowly release those drugs over a period of time that we could control.”

Currently, doctors typically have two choices for administering drugs to the eye: eye drops and injection with a traditional hypodermic needle into the vitreous at the center of the eye. While injections into the vitreous do reach their target, they also affect other portions of the eye where the drug may not be desirable. Eye drops, which are simple to use, often fail to reach the structures being targeted, Prausnitz said.

Henry Edelhauser, a professor of ophthalmology at Emory School of Medicine, said pharmaceutical companies are now developing new compounds to treat eye diseases. Those drugs will be most effective if they can be delivered directly to the portion of the eye that requires treatment, such as the choroid and retina that this new delivery method targets.

“With this technique, we are keeping the drug right where it needs to be for most therapies of interest in the back of the eye,” he said.

The microneedles used in the technique are made of stainless steel and are less than one millimeter long. The researchers believe that they will cause less trauma to the eye than the larger hypodermic needles, and reduce the risk of infection.

The model compounds used in this study fluoresced inside the eye, showing researchers that they had reached their targets. But the compounds studied were not drugs, so the next step, according to Edelhauser, will be to study how well the microneedle technique can get real drugs to the eye structures of interest.

The technology has been licensed to an Atlanta-based startup, Clearside Biomedical, which plans to advance the micro-injection technology developed in collaboration between the research groups of Mark Prausnitz at Georgia Tech and Henry Edelhauser at Emory.

Microneedle

Researcher Samirkumar Patel displays a prototype microneedle used to inject therapeutics into specific locations in the eye. The technology could allow doctors to target drugs to locations in the eye that are now difficult to reach. Image: Gary Meek

Source: Georgia Institute of Technology

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Scientists show new compound virtually eliminates HIV in cell culture

A new study by scientists on the Florida campus of The Scripps Research Institute shows, in cell culture, a natural compound can virtually eliminate human immunodeficiency virus (HIV) in infected cells. The compound defines a novel class of HIV anti-viral drugs endowed with the capacity to repress viral replication in acutely and chronically infected cells.

The HIV/AIDS pandemic continues to affect 34 million individuals worldwide, including more than 3 million children, according to the World Health Organization. Current treatment involves the use of several antiretroviral drugs, termed Highly Active Antiretroviral Therapy (HAART), which can extend the life expectancy of HIV-positive individuals and decrease viral load without, however, eradicating the virus.

“We know that there are reservoirs of HIV that aren’t being eliminated by current treatment and that keep replenishing the infection,” said Susana Valente, a Scripps Research biologist who led the study. “Viral production from these cellular reservoirs that harbor an integrated viral genome is not affected by current antiretroviral drugs, which only stop novel rounds of infection. The compound in the current study virtually eliminates all viral replication from already-infected cells where HIV hides.”

The new study, published in the July 20, 2012 issue of the journal Cell Host and Microbe, focused on a medically promising compound known as Cortistatin A. This natural product was isolated in 2006 from a marine sponge, Corticium simplex, discovered more than 100 years ago. In 2008, Scripps Research chemist Phil Baran and his team won the global race to synthesize the compound, presenting an efficient and economical method.

In the new study, Valente and her colleagues collaborated with the Baran lab, using a synthetic version of the compound, didehydro-Cortistatin A, to study the compound’s effect on two strains of HIV. The strains were HIV-1, the most common form of the virus, and HIV-2, which is concentrated in West Africa and some parts of Europe.

The results showed that the compound reduced viral production by 99.7% from primary CD4+T cells (a type of immune cell) isolated from patients without levels of the virus in their bloodstream and who had been under HAART treatment for a long period of time. When the compound was added to other antiviral treatments, it further reduced by 20 percent viral replication from CD4+T cells isolated from patients with detectable amounts of virus in their bloodstreams.

The inhibitor works by binding tightly to the viral protein known as Tat, a potent activator of HIV gene expression, effectively preventing the virus from replicating even at miniscule concentrations—making it the most potent anti-Tat inhibitor described to date, Valente said.

Another interesting feature of this compound is that withdrawal of the drug from cell culture does not result in virus rebound, which is normally observed with other antiretrovirals.

While most antiretroviral compounds block only new infections, didehydro-Cortistatin A reduces viral replication from already-infected cells, potentially limiting cell-to-cell transmission.

The new inhibitor already has a drug-like structure, is effective at very low concentrations, and has no toxicity associated with it, at least at the cellular level, the study noted.

The first author of the study “Potent Suppression of Tat-dependent HIV Transcription by didehydro-Cortistatin A” is Guillaume Mousseau of Scripps Research. In addition to Valente and Baran, other authors include Mark A. Clementz, Wendy N. Bakeman, Nisha Nagarsheth, Michael Cameron, and Jun Shi of Scripps Research; and Rémi Fromentin and Nicolas Chomont of the Vaccine and Gene Therapy Institute.

The study was supported by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) and the Landenberger Foundation.

The Scripps Research Institute

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Artificial jellyfish built from rat cells

 

Bioengineers have made an artificial jellyfish using silicone and muscle cells from a rat’s heart. The synthetic creature, dubbed a medusoid, looks like a flower with eight petals. When placed in an electric field, it pulses and swims exactly like its living counterpart.

“Morphologically, we’ve built a jellyfish. Functionally, we’ve built a jellyfish. Genetically, this thing is a rat,” says Kit Parker, a biophysicist at Harvard University in Cambridge, Massachusetts, who led the work. The project is described today in Nature Biotechnology1.

Parker’s lab works on creating artificial models of human heart tissues for regenerating organs and testing drugs, and the team built the medusoid as a way of understanding the “fundamental laws of muscular pumps”. It is an engineer’s approach to basic science: prove that you have identified the right principles by building something with them.

A jellyfish made of silicone and rat heart cells ‘swims’ in water when subjected to an electric field.HARVARD UNIV./CALTECH

In 2007, Parker was searching for new ways of studying muscular pumps when he visited the New England Aquarium in Boston, Massachusetts. “I saw the jellyfish display and it hit me like a thunderbolt,” he says. “I thought: I know I can build that.” To do so, he recruited John Dabiri, a bioengineer who studies biological propulsion at the California Institute of Technology (Caltech) in Pasadena. “I grabbed him and said, ‘John, I think I can build a jellyfish.’ He didn’t know who I was, but I was pretty excited and waving my arms, and I think he was afraid to say no.”

Janna Nawroth, a graduate student at Caltech who performed most of the experiments, began by mapping every cell in the bodies of juvenile moon jellies (Aurelia aurita) to understand how they swim. A moon jelly’s bell consists of a single layer of muscle, with fibres that are tightly aligned around a central ring and along eight spokes.

To make the bell beat downwards, electrical signals spread through the muscle in a smooth wave, “like when you drop a pebble in water”, says Parker. “It’s exactly like what you see in the heart. My bet is that to get a muscular pump, the electrical activity has got to spread as a wavefront.”

Form and function

Nawroth created a structure with the same properties by growing a single layer of rat heart muscle on a patterned sheet of polydimethylsiloxane. When an electric field is applied across the structure, the muscle contracts rapidly, compressing the medusoid and mimicking a jellyfish’s power stroke. The elastic silicone then pulls the medusoid back to its original flat shape, ready for the next stroke.

When placed between two electrodes in water, the medusoid swam like the real thing. It even produced water currents similar to those that wash food particles into jellyfish’s mouths. “We thought if we’re really good at this, we’re going to recreate that vortex, and we did,” says Parker. “We took a rat apart and rebuilt it as a jellyfish.”

“I think that this is terrific,” says Joseph Vacanti, a tissue engineer at Massachusetts General Hospital in Boston. “It is a powerful demonstration of engineering chimaeric systems of living and non-living components.”

Parker says his team is taking synthetic biology to a new level. “Usually when we talk about synthetic life forms, somebody will take a living cell and put new genes in. We built an animal. It’s not just about genes, but about morphology and function.”

The team now plans to build a medusoid using human heart cells. The researchers have filed a patent to use their design, or something similar, as a platform for testing drugs. “You’ve got a heart drug?” says Parker. “You let me put it on my jellyfish, and I’ll tell you if it can improve the pumping.”

They also hope to reverse-engineer other marine life forms, says Parker. “We’ve got a whole tank of stuff in there, and an octopus on order.”

Nature

 doi:10.1038/nature.2012.11046

References

  1. Nawroth, J. C. et al. Nature Biotechol. http://dx.doi.org/10.1038/nbt.2269 (2012).

 

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NIH tools facilitate matching cancer drugs with gene targets

NIH tools facilitate matching cancer drugs with gene targets

A new study details how a suite of web-based tools provides the research community with greatly improved capacity to compare data derived from large collections of genomic information against thousands of drugs. By comparing drugs and genetic targets, researchers can more easily identify pharmaceuticals that could be effective against different forms of cancer.

The newly updated software, called CellMiner, was built for use with the NCI-60, one of the most widely utilized collections of cancer cell samples employed in the testing of potential anti-cancer drugs. The tools, available free, provide rapid access to data from 22,379 genes catalogued in the NCI-60 and from 20,503 previously analyzed chemical compounds, including 102 U.S. Food and Drug Administration-approved drugs.

The study, written by the scientists that developed the tools at the National Cancer Institute (NCI), part of the National Institutes of Health, appeared in the July 16, 2012, issue of Cancer Research.

“Previously you would have to hire a bioinformatics team to sort through all of the data, but these tools put the entire database at the fingertips of any researcher,” explained Yves Pommier, M.D., Ph.D., of the NCI’s Center for Cancer Research. “These tools allow researchers to analyze drug responses as well as make comparisons from drug to drug and gene to gene.”

Genomic sequencing and analysis have become increasingly important in biomedicine, but they are yielding data sets so vast that researchers may find it difficult to access and compare them. As new technologies emerge and more data are generated, tools to facilitate the comparative study of genes and potentially promising drugs will be of even greater importance. With the new tools, available at http://discover.nci.nih.gov/cellminer, researchers can compare patterns of drug activity and gene expression, not only to each other but also to other patterns of interest. CellMiner allows the input of large quantities of genomic and drug data, calculates correlations between genes and drug activity profiles, and identifies correlations that are statistically significant. Its data integration capacities are easier, faster, and more flexible than other available methods, and these tools can be adapted for use with other collections of data.

Researchers looking at a particular drug can use the tools to access data from previous experiments done on that drug and analyze how the drug relates to other drugs and various gene profiles. As a case example for this study, the researchers compared drug activity levels and gene expression patterns from previous research to identify an investigational compound, called NSC732298, which is not currently being studied for colon cancer, but could be a potential therapy for the disease based on a CellMiner gene-drug match. In the same exercise, the researchers were able to identify that a second investigational drug that is being tested for colon cancer, called selumetinib, might also be effective against melanoma.

“We’re looking forward to seeing how other people are going to use this tool to look at gene co-regulation, regulation of gene expression, and the relationship between gene expression and cancer,” said Pommier.

This work was supported by NCI’s Center for Cancer Research and Division of Cancer Treatment and Diagnosis under intramural project number ZIA BC 006150.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference: Reinhold WC, Sunshine M, Liu H, Varma S, Kohn KW, Morris J, Doroshow J, and Pommier Y. Web-based genomic and pharmacologic tools for gene and microRNA transcript levels, drug activities, and their pattern comparisons across the NCI-60. Cancer Research. July 16, 2012.

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NCI spotlights cancer gene-drug matchmaker software

An updated set of web-based analysis tools rapidly finds drugs with the potential to combat certain cancers, matching the drugs with tumors based on vast amounts of genetic information about the cancers and data on thousands of tested compounds. The NIH’s National Cancer Institute developed the software called CellMiner for use with its extensive collection of cancer cell samples, but researchers anywhere can use the tools for free as they drill into existing and new datasets to identify anti-cancer drugs.

If the nirvana of personalized medicine is to match patients with the right drugs based on the specific genetic traits of their disease, the NCI has advanced some technology in CellMiner to help realize that ideal in oncology.

The software takes advantage of the way new drugs are developed to target specific genes rather than entire organs where cancers crop up, enabling researchers to find uses of drugs in whichever tumor type the misfit genes appear. For instance, researchers used CellMiner to uncover that an experimental drug called selumetinib, which has been trialed in patients with colon cancer, might also work as an attack against deadly skin cancer or melanoma. The findings were published in the journal Cancer Research.

The NCI’s tools have been developed with information overload in mind. Drug researchers have access to many massive datasets on cancer genomes and other molecular information to aid their hunt for new treatments, yet some of the existing analysis software might require scads of bioinformatics specialists to correlate target gene data with information on compounds. And the NCI says that CellMiner is easier to use than those previous tools. The ease of use alone could speed up data-driven discovery of potential cancer drugs.

“Previously you would have to hire a bioinformatics team to sort through all of the data, but these tools put the entire database at the fingertips of any researcher,” the NCI’s Dr. Yves Pommier said in a statement. “These tools allow researchers to analyze drug responses as well as make comparisons from drug to drug and gene to gene.”

– here’s the release
– see the abstract

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Researchers develop first software simulation of an entire organism

Drawing on data from more than 900 scientific papers, scientists at Stanford have produced a complete computational model of the bacterium Mycoplasma genitalium. Researchers say the work will yield new insights into basic cellular principles and vastly speed up the scientific process.

The model was recently published in Cell, and a recent Stanford Report article describes the significance of the work:

By encompassing the entirety of an organism in silico, the paper fulfills a longstanding goal for the field. Not only does the model allow researchers to address questions that aren’t practical to examine otherwise, it represents a stepping-stone toward the use of computer-aided design in bioengineering and medicine.

“This achievement demonstrates a transforming approach to answering questions about fundamental biological processes,” said James M. Anderson, director of the National Institutes of Health Division of Program Coordination, Planning and Strategic Initiatives. “Comprehensive computer models of entire cells have the potential to advance our understanding of cellular function and, ultimately, to inform new approaches for the diagnosis and treatment of disease.”

Photo by Erik Jacobsen, Covert Lab

Source:http://scopeblog.stanford.edu/2012/07/23/researchers-develop-first-software-simulation-of-an-entire-organism/

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They all said : Try to live together peacefully !

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The Best Treks In The World

These 10 classic treks are for serious walkers. All of them require a sturdy pair of lungs, fit legs and a good amount of preparation. However, if you choose to go on any of these trails then you will be rewarded with experiences that last a lifetime. In no particular order:

1. GR20, France


Image by Jean-Baptiste Bellet

This demanding 15- day (168km, 104mi) slog through Corsica is legendary for the diversity of landscapes it traverses. There are forests, granite moonscapes, windswept craters, glacial lakes, torrents, peat bogs, maquis, snow-capped peaks, plains and névés (stretches of ice formed from snow). But it doesn’t come easy: the path is rocky and sometimes steep, and includes rickety bridges and slippery rock faces – all part of the fun. Created in 1972, the GR20 links Calenzana, in the Balagne, with Conca, north of Porto Vecchio.

2. Inca Trail, Peru


Image by funkz

This 33km (20mi) ancient trail was laid by the Incas and is currently traversed by thousands each year. The trail leads from the Sacred Valley to Machu Picchu winding its way up and down and around the mountains, taking three high passes en route. Views of white-tipped mountains and high cloud forest combine with the magic of walking from one cliff-hugging ruin to the next – understandably making this South America’s most famous trail.

3. Pays Dogon, Mali


Image by Crazy Joe Devola

‘The land of the Dogon people’ is one of Africa’s most breathtaking regions. A trek here can last anywhere between two and 10 days, and takes in the soaring cliffs of the Bandiagara escarpment inlaid with old abandoned cliff dwellings. Dogon villages dot the cliffs and are an extraordinary highlight of the journey. The Dogon are known for their masked stilt dancers, intricately carved doors and pueblo-like dwellings built into the side of the escarpment.

4. Everest Base Camp, Nepal


Image by lampertron

Reaching a height of 5,545m (18,193ft) at Kala Pattar, this three-week trek is extremely popular with those who want to be able to say, ‘I’ve been to the base of the world’s highest mountain’. The difficult trek passes undeniably spectacular scenery and is trafficked by Sherpa people of the Solu Khumbu. The heights reached during this trek are literally dizzying until you acclimatise to the altitude, and the continuous cutting across valleys certainly has its ups and downs.

5. Indian Himalayas, India


Image by Chandramohan Burly V

Fewer folk trek on the Indian side of the world’s greatest mountain range. So, if isolation’s your thing try trekking in Himachal Pradesh. Hardcore hikers can try teetering along the mountain tops for 24 days from Spiti to Ladakh. This extremely remote and challenging walk follows ancient trade routes. The bleak high-altitude desert terrain inspired Rudyard Kipling to exclaim, ‘Surely the gods live here; this is no place for men’.

6. Overland Track, Australia


Image by brewbooks

Tasmania’s prehistoriclooking wilderness is most accessible on the 80km (50mi, five- to six-day) Overland Track. Snaking its way between Cradle Mountain and Lake St Clair (Australia’s deepest natural freshwater lake), the well-defined path (boardwalked in parts) passes craggy mountains, beautiful lakes and tarns, extensive forests and moorlands. Those who want more can take numerous side walks leading to waterfalls, valleys and still more summits including Mt Ossa (1,617m, 5,305ft) – Tassie’s highest.

7. Routeburn Track, New Zealand


Image by kiwinz

See the stunning subalpine scenery of New Zealand’s South Island surrounding this medium three-day (32km, 20mi) track. At the base of New Zealand’s Southern Alps, the track passes through two national parks: Fiordland and Mt Aspiring. Highlights include the views from Harris Saddle and atop Conical Hill – from where you can see waves breaking on the distant beach. The main challenge for this popular hike is actually securing a place among the limited numbers who are allowed on the track at any time.

8. The Narrows, USA


Image by Adam Belles

A 26km (16mi) journey through dramatic canyons carved over centuries by the Virgin River, the Narrows in Zion National Park is a hike like no other. The route is the river, with over half of the hike spent wading and sometimes swimming. The hike can be traversed in a day, though some choose to take the hanging gardens and natural springs at a more leisurely pace – spending a night at one of the park’s 12 camp grounds.

9. The Haute Route, France-Switzerland


Image by perry_maurice

Leading from Chamonix in France through the southern Valais to Zermatt in Switzerland, the Haute Route traverses some of the highest and most scenic country accessible to walkers anywhere in the Alps. The summer Haute Route walk (which takes a different course than the more famous winter skitouring route) takes around two weeks to complete. It mainly involves ‘pass hopping’ and demands a high level of fitness, with every section containing a high huff factor.

10. Baltoro Glacier & K2, Pakistan


Image by mariachily

This corridor of ice leads to the colossal peak of K2 (8,611m, 28,251ft), the world’s second-highest peak. This incomparable trek traverses some of the most humbling scenery on the planet. What begins following icy rivers boldly goes to the guts of the glacier before leading to the granite pyramidal mountains including Paiju (6,610m, 21,686ft), Uli Biaho (6,417m, 21,053ft), Great Trango Tower (6,286m, 20,623ft) and ultimately K2. If the 15 days doesn’t floor you, take side trips to more moraine-covered glaciers.

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The Science of Success

1) How to Break Bad Habits

If you are trying to stop smoking, swearing, or chewing your nails, you have probably tried the strategy of distracting yourself – taking your mind off whatever it is you are trying not to do – to break the habit. You may also have realized by now that it doesn’t work. Distraction is a great way to resist a passing temptation, but it turns out to be a terrible way to break a habit that has really taken hold.

That’s because habit-behaviors happen automatically – often, without our awareness. So thinking about George Clooney isn’t going to stop me from biting my nails if I don’t realize I’m doing it in the first place.

What you need to do instead is focus on stopping the behavior before it starts (or, as psychologists tend to put it, you need to “inhibit” your bad behavior). According to research by Jeffrey Quinn and his colleagues, the most effective strategy for breaking a bad habit is vigilant monitoring – focusing your attention on the unwanted behavior to make sure you don’t engage in it. In other words, thinking to yourself “Don’t do it!” and watching out for slipups – the veryopposite of distraction. If you stick with it, the use of this strategy can inhibit the behavior completely over time, and you can be free of your bad habit for good.

2) How to Make Everything Seem Easier

Most of us have grown accustomed to the idea that our moods, and even our judgments, can be influenced by unrelated experiences of sight and sound – we feel happier on sunny days, more relaxed when listening to certain kinds of music, and more likely to lose our tempers when it’s hot and humid. But very few of us have even considered the possibility that our tactile experience – the sensations associated with the things we touch, might have this same power.

New research by Joshua Ackerman, Christopher Nocera, and John Bargh shows that the weight, texture, and hardness of the things we touch are, in fact, unconsciously factored into our decisions about things that have nothingto do with what we are touching.

For instance, we associate smoothness and roughness with ease and difficulty, respectively, as in expressions like “smooth sailing,” and “rough road ahead.” In one study, people who completed a puzzle with pieces that had been covered in sandpaper later described an interaction between two other individuals as more difficult and awkward than those whose puzzles had been smooth.

3) How To Manage Your Time Better

Good time management starts with figuring out what tasks you need to accomplish, and how long each will take. The problem is, human beings are generally pretty lousy when it comes to estimating the time they will need to complete any task. Psychologists refer to this as the planning fallacy, and it has the very real potential to screw up our plans and keep us from reaching our goals.

New research by Mario Weick and Ana Guinote shows that, somewhat ironically, people in positions of power are particularly poor planners. That’s because feeling powerful tends to focus us on getting what we want, ignoring the potential obstacles that stand in our way. The future plans of powerful people often involve “best-case scenarios,” which lead to far shorter time estimates than more realistic plans that take into account what might go wrong.

The good news is, you can learn to more accurately predict how long something will take and become a better planner, if you stop and consider potential obstacles, along with two other factors: your own past experiences (i.e., how long did it take last time?), and all the steps or subcomponents that make up the task (i.e., factoring in the time you’ll need for each part.)

4) How to Be Happier

Most of us tend to think that if we just had a bit more money we’d get more satisfaction out of life, but on the whole, this turns out not to be true. So whydoesn’t money make us happier? New research by Jordi Quoidbach and colleagues suggests that the answer lies, at least in part, in how wealthier people lose touch with their ability to savor life’s pleasures.

Savoring is a way of increasing and prolonging our positive experiences. Taking time to experience the subtle flavors in a piece of dark chocolate, imaging the fun you’ll have on an upcoming vacation (and leafing through your trip photos afterward), telling all your friends on Facebook about the hilarious movie you saw over the weekend – these are all acts of savoring, and they help us to squeeze every bit of joy out of the good things that happen to us.

Why, then, don’t wealthier people savor, if it feels so good? It’s obviously not for a lack of things to savor. The basic idea is that when you have the money to eat at fancy restaurants every night and buy designer clothes from chic boutiques, those experiences diminish the enjoyment you get out of the simpler, more everyday pleasures, like the smell of a steak sizzling on your backyard grill, or the bargain you got on the sweet little sundress from Target.

Create plans for how to inject more savoring into each day, and you will increase your happiness and well-being much more than (or even despite) your growing riches. And if you’re riches aren’t actually growing, then savoring is still a great way to truly appreciate what you do have.

5) How to Have More Willpower

Do you have the willpower to get the job done, or have you found yourself giving in to temptations, distractions, and inaction when trying to reach your own goals? If it’s the latter, you’re not alone. But more importantly, you can do something about it. New research by Mark Muraven shows that our capacity for self-control is surprisingly like a muscle that can be strengthened by regular exercise.

Do you have a sweet tooth? Try giving up candy, even if weight-loss and cavity-prevention are not your goals. Hate exerting yourself physically? Go out and buy one of those handgrips you see the muscle men with at the gym – even if your goal is to pay your bills on time. In one study, after two weeks of sweets-abstinence and handgripping, Muraven found that participants had significantly improved on a difficult concentration task that required lots of self-control.

Just by working your willpower muscle regularly, engaging in simple actions that require small amounts of self-control – like sitting up straight or making your bed each day – you can develop the self-control strength you’ll need to tackle all of your goals.

6) How to Choose a Mate

What role does personality play in creating marital bliss? More specifically, is it your personality, yourpartner’s personality, or the similarity between the two that really matters when it comes to being happy in your marriage? A study of over 10,000 couples from three countries provides us with some answers.

Your own personality is in fact a powerful predictor of your marital satisfaction. People who were more agreeableconscientious, and emotionally stablereported being significantly happier with their spouse. That spouse’s personality was also a reliable, though slightly less powerful, predictor of relationship satisfaction. Keep these same traits – the “Big 3” for happiness in a marriage – in mind when you are seeking Mr. or Ms. Right.

Finally, there’s personality similarly – which, as it happens, doesn’t seem to matter at all. The extent to which married couples matched one another on the Big Five traits had no predictive power when it came to understanding why some couples are happy together and others not. This is not to say that having similar goals or values isn’t important – just that having similar personalities doesn’t seem to be.

So if you are outgoing and your partner is shy, or if you are adventurous and your partner doesn’t really like to try new things, it doesn’t mean you can’t have a satisfying marriage. Whether you are birds of a feather, or opposites that attracted, you are equally likely to live a long and happy life together.

Just try to be generally pleasant, responsible, and even-tempered, and find someone willing to do the same.

7) How to Feel More Powerful

In the animal kingdom, alphas signal their dominance through body movement and posture. Human beings are no different. The most powerful guy in the room is usually the one whose physical movements are most expansive – legs apart, leaning forward, arms spread wide while he gestures. He’s the CEO who isn’t afraid to swing his feet up onto the conference room table, hands behind his head and elbows jutting outward, confident in his power to spread himself out however he damn well pleases.

The nervous, powerless person holds himself very differently – he makes himself physically as small as possible: shoulders hunched, feet together, hands in his lap or arms wrapped protectively across his chest. He’s the guy in the corner who is hoping he won’t be called on, and often is barely noticed.

We adopt these poses unconsciously, and they are perceived (also unconsciously) by others as indictors of our status. But a new set of studies by Dana Carney, Amy Cuddy, and Andy Yap reveals that the relationship between power and posing works in both directions. In other words, holding powerful poses can actually make you more powerful.

In their studies, posing in “high power” positions not only created psychological and behavioral changes typically associated with powerful people, it createdphysiological changes characteristic of the powerful as well. High power posers felt more powerful, were more willing to take risks, and experienced significant increases in testosterone along with decreases in cortisol (the body’s chemical response to stress.)

If you want more power – not just the appearance of power, but the genuinefeeling of power – then spread your limbs wide, stand up straight, and lean into the conversation. Carry yourself like the guy in charge, and in a matter of minutes your body will start to feel it, and you will start to believe it.

8) How To Tell If He Loves You

“If he really loved me, then he would…”

Everyone who’s ever been in a relationship has had thoughts like this one. If he loved me he would bring me flowers, or compliment me more often, or remember my birthday, or remember to take out the damn garbage. We expect feelings of love to translate directly into loving behaviors, and often judge the quality and intensity of our partner’s feelings through their more tangible expressions. When it comes to love, actions speak louder than words, right?

Well, not necessarily. According to new research by psychologists Lara Kammrath and Johanna Peetz, romantic feelings like love, intimacy, and commitment reliably lead to some loving behaviors, but not others. In their studies, love predicted spontaneous, in-the-moment acts of kindness andgenerosity, like saying “I love you,” offering a back rub, or surprising your partner with a gourmet dinner – the kinds of loving actions that don’t require much in the way of forethought, planning, or memory.

On the other hand, love does a lousy job of predicting the kinds of “loving” behaviors that are harder to perform, often because they have to be maintained over longer periods of time (e.g., remembering to do household chores without being asked, being nice to one’s in-laws) or because there is a delay between the thought and the action (remembering to buy your wife a gift for her birthday next week, keeping a promise call home during your conference in Las Vegas.). When it comes to the harder stuff, it’s how conscientious you are, rather than how much in love you are, that really matters.

So if you’re trying to get a sense of how your partner really feels about you, the smaller, spontaneous acts of love that occur without much forethought are a much better indicator of the depth of his love than whether or not he remembers your birthday or to take out the trash.

9) How to Make It Easier to Cut Your Losses

Sometimes, we don’t know when to throw in the towel. As a project unfolds, it becomes clear that things aren’t working out as planned, that it will cost too much or take too long, or that someone else will beat you to the punch. But instead of moving on to new opportunities, we continue to devote our time, energy, and money to doomed projects (or even doomed relationships), digging a deeper hole rather than trying to climb our way out of it.

Why? The most likely culprit is our overwhelming aversion to sunk costs – the resources that we’ve put into an endeavor that we can’t get back out. We worry far too much about what we’ll lose if we just move on, and not nearly enough about the costs of not moving on – more wasted time and effort, and more missed opportunities.

But thanks to recent research by Daniel Molden and Chin Ming Hui, there is a simple way to be sure you are making the best decisions when your endeavor goes awry: focus on what you have to gain, rather than what you have to lose.

Psychologists call this adopting a promotion focus. When Molden and Hui had participants think about theirgoals in terms of potential gains, they became more comfortable with accepting the losses they had to incur along the way. When they adopted a prevention focus, on the other hand, and thought about their goals in terms of what they could lose if they didn’t succeed, they were much more sensitive to sunk costs.

If you make a deliberate effort to refocus yourself prior to making your decision, reflecting on what you have to gain by cutting your losses now, you’ll find it much easier to make the right choice.

10) How to Fight With Your Spouse

Having a satisfying, healthy relationship with your partner doesn’t mean never fighting – it means learning to fight well. But what is the best way for two people to cope with their anger, frustration, and hurt, without undermining their mutual happiness?

Thankfully, recent research by James McNulty and Michelle Russell provides the answer. The best way to deal with conflict in a marriage, it turns out, depends on how serious or severe the problem is. Did your spouse drink too much at the party last night, or is he drinking too much every night? Did she splurge a little too much on clothes last month, or are her spending habits edging you closer and closer to bankruptcy? Did he invite his mother to dinner without discussing it with you first, or did he invite his mother to live with youwithout discussing it first? Little problems and big problems require very different approaches if you want to have a lasting, happy marriage.

When it comes to minor problems, direct fighting strategies – like placing blame on your spouse for their actions or expressing your anger – results in a loss of marital satisfaction over time. Flying off the handle when he forgets to pick up the dry cleaning yet again, or when she spends a little too much money on a pricey pair of shoes, is going to take its toll on your happiness in the long run. You really are better off letting the small stuff go.

In response to major problems, however, these same direct fighting strategies predict increased marital satisfaction! Expressing your feelings, blaming your partner and demanding that they change their ways will lead to greater happiness when the conflict in question is something significant – something that if left unresolved could ultimately tear your relationship apart.

Issues involving addiction, financial stability, infidelity, child-rearing, and whether or not you live with your mother-in-law need to be addressed, even if it gets a little ugly. Couples who battle it out over serious issues do a better job of tackling, and eventually resolving those issues, than those who swept big problems under the carpet.

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Medical Tales

These are true tales from the medical profession.

A man comes into the ER and yells, “My wife’s going to have her baby in the cab!” I grabbed my stuff, rushed out to the cab, lifted the lady’s dress, and began to take off her underwear. Suddenly I noticed that there were several cabs, and I was in the wrong one.

Dr. Mark MacDonald, San Antonio, TX

 

At the beginning of my shift I placed a stethoscope on an elderly and slightly deaf female patient’s anterior chest wall. “Big breaths,” I instructed. “Yes, they used to be,” remorsed the patient.

Dr.Richard Byrnes, Seattle, WA

 

One day I had to be the bearer of bad news when I told a wife that her husband had died of a massive myocardial infarct. Not more than five minutes later, I heard her reporting to the rest of the family that he had died of a “massive internal fart.”

Dr. Susan Steinberg, Manitoba, Canada

 

I was performing a complete physical, including the visual acuity test. I placed the patient twenty feet from the chart and began, “Cover your right eye with your hand.” He read the 20/20 line perfectly

“Now your left.” Again, a flawless read.

“Now both,” I requested.

There was silence. He couldn’t even read the large E on the top line. I turned and discovered that he had done exactly what I had asked; he was standing there with both his eyes covered. I was laughing too hard to finish the exam.

Dr. Matthew Theodropolous, Worcester, MA

 

During a patient’s two week follow-up appointment with his cardiologist, he informed me, his doctor, that he was having trouble with one of his medications. “Which one?” I asked. “The patch. The nurse told me to put on a new one every six hours and now I’m running out of places to put it!” I had him quickly undress and discovered what I hoped I wouldn’t see… Yes, the man had over fifty patches on his body! Now the instructions include removal of the old patch before applying a new one.

Dr. Rebecca St. Clair, Norfolk, VA

 

I was caring for a woman from Kentucky and asked, “So how’s your breakfast this morning?” “It’s very good, except for the Kentucky Jelly. I can’t seem to get used to the taste,” the patient replied. I then asked to see the jelly and the woman produced a foil packet labelled “KY Jelly.”

Dr. Leonard Kransdorf, Detroit, MI

 

A Nurse was on duty in the Emergency Room, when a young woman with purple hair styled into a punk rocker Mohawk, sporting a variety of tattoos, and wearing strange clothing, entered. It was quickly determined that the patient had acute appendicitis, so she was scheduled for immediate surgery. When she was completely disrobed on the operating table, the staff noticed that her pubic hair had been dyed green, and above it there was a tattoo that read, “Keep off the grass.” Once the surgery was completed, the surgeon wrote a short note on the patient’s dressing, which said “Sorry, had to mow the lawn.” 

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Best Places to Live for Escaping World Conflict

Where would you be the safest if World War 3 broke out tomorrow? Perhaps it’s a grim subject, but safety and distance from world conflict can be a motivating factor in your choice to expatriate. At the very least, conflict around the world can weigh heavy on the soul, and it’s nice to know there are some places still left in the world where you might be left in peace. Thus, we’ve assembled a list of the 10 best places to live if you want to escape world conflict.

10. Switzerland

switzerland

Switzerland’s long history of neutrality and its tucked away location among the valleys of the Alps still make it a safe bet, even despite having a high number of bordering nations. It helps that neighboring Austria is also considered a neutral nation.

 

9. Costa Rica

Costa Rica

Costa Rica has a stable democracy, a disbanded military and a national policy of neutrality. It also ranks highly on the Global Peace Index, Happy Planet Index, and Life Satisfaction Index. Although it sits in the middle of a tumultuous region, there are far worse places to sit in peace as the world goes down in flames all around.

8. Papua New Guinea

papua

There are regions of Papua New Guinea that are still being discovered for the first time. The canopy covered, mountainous nation contains some of the most isolated places in the world. Tuck yourself away in a nook here and it may be one of the few places left where you can completely insulate yourself from the outside world.

7. Canada

Canada

Canada is the second largest nation in the world, yet it only shares a land border with one other country– the U.S.A.– and it is a peaceful border. That means there is a great expanse to escape to, if need be. Furthermore, Canada has few world enemies, ranks consistently high on the Global Peace Index, and is relatively homogeneous.

6. Seychelles

Seychelles

Aside from being safely isolated from the rest of the world in the middle of the Indian Ocean, this beautiful island nation is a great place to forget about your worries. Isolation is the key here. And conflict is as transparent as the water.

5. Finland

finland

Finland has a long history of desiring to stay out of international conflicts, is recognized as neutral and always ranks in the top 10 of the Global Peace Index. It’s northerly location also typically means the remote areas of this country are a perfect place to disappear.

4. Tuvalu

Tuvalu

Isolated in the middle of Micronesia, Tuvalu is among the safest and most remote places in the world. It is the third least populated country on Earth, and the forth smallest. There are only a few places more distant from the world’s strife than Tuvalu.

3. Iceland

iceland

Iceland, of course, has no borders, has remote locations, is stable as a country and has virtually no world enemies. Its people are happy and the nation always ranks highly on the Global Peace Index. If world conflict erupts, Iceland is one of the few stable nations in the world unlikely to get caught up in the middle.

2. Bhutan

Bhutan

Landlocked among the Himalaya mountains, Bhutan is one of the most isolated nations in the world. It also showcases one of the most stable balances in the world between moderization and retention of ancient culture. Its religious population believes in peaceful resolution to all conflict, and although it sits in a troubled region, it remains protected by its geography.

1. New Zealand

New Zealand

New Zealand might be the most isolated and expansive fully developed nation in the world. It shares no borders, sits relatively distant from any other nation, has no real national enemies, has a safe democracy and a diverse landscape with many remote places to hide away within. Furthermore, it ranked #1 on the Global Peace Index in 2009.

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The most infamously outlawed novels – Top 10 Banned Books

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Throughout history, fiction has always rattled the cages of the censors. Whether it be themes of politics, religion, or it just has a lot of sex in it, people the world over have shook their fists at an author at one time or another. But, in today’s book friendly society (thanks Steve Jobs!) we can now read about complex themes of heavy handed governments, violence, and drugs without the fear of being tapped on the shoulder by “the man”. To celebrate this fact, we’ve collected our ten favourite books, that have been hauled off the shelves in favour of something more wholesome.Brave New World by Aldous Huxley (1932)

1. BRAVE NEW WORLD BY ALDOUS HUXLEY (1932)

The gist: Written in 1931 and published a year later, Huxley’s parody of H. G. Wells’ utopian future in his novel, Men Like Gods isn’t wholly dissimilar to George Orwell’s 1984. Addressing the period’s core theme of industrialisation, Huxley explored the loss of identity and increasing dividision of society to devastating effect.

Why was it banned? Initially, Ireland pulled it off the shelves for its controversial themes on child birth, before several states in the US tried to have it removed from school curriculums due to its “themes on negativity.”

The Grapes of Wrath by John Steinbeck (1939)

2. THE GRAPES OF WRATH BY JOHN STEINBECK (1939)

The gist: Steinbeck’s Pullitzer Prize winning novel, released in 1939, told the all too familiar story of the effects of the Great Depression on the rural poor. Focusing on a family of sharecroppers, the Joads, who were driven from their Oklahoma home by drought, economic hardship, and changes in the agriculture industry. With nowhere left to turn, they set out for California along with thousands of other “Okies” in search of land, jobs and dignity.

Why was it banned? Despite the book being championed by the literary elite, it was publicly banned in the US and burned en masse by the general population. People were shocked by its description of the poor, which Steinbeck later admitted was a sanitised version of what was really going on in these remote communities.

Tropic of Cancer by Henry Miller (1934)

3. TROPIC OF CANCER BY HENRY MILLER (1934)

The gist: Set in France during the 1930s, the book follows the life of its author, Miller, who at the time was a struggling writer. Written in the first person, he wrote about his sexual encounters with friends and colleagues, it was an expose on the lives of American expats living abroad.

Why was it banned? Almost as soon as it was released, the Pennsylvania Supreme Court Justice Michael Musmanno wrote Cancer is, “not a book. It is a cesspool, an open sewer, a pit of putrefaction, a slimy gathering of all that is rotten in the debris of human depravity.” As you can imagine, people weren’t ready for what George Orwell would later call “the most important book of the mid-1930s”.

Slaughterhouse-Five by Kurt Vonnegut (1969)

4. SLAUGHTERHOUSE-FIVE BY KURT VONNEGUT (1969)

The gist: Billy Pilgrim, a disoriented, and ill-trained American soldier, is captured by the Germans during the Battle of the Bulge and taken prisoner in Dresden. Housed in a disused slaughterhouse, known as “Slaughterhouse number 5”, he and the other POWs and German guards alike hide in a deep cellar; sheltering from the firestorm during the Bombing of Dresden in World War II. During this period, time begins to warp, and Pilgrim starts to see visions of the future and the past, including his death.

Why was it banned? The good old USA thought better than to let its children be exposed to such themes, residing it to the ranks of the American Library Association’s 100 Most Frequently Challenged books.

The Satanic Verses by Salman Rushdie (1988)

5. THE SATANIC VERSES BY SALMAN RUSHDIE (1988)

The gist: Rushdie’s book tells the story of an Indian expat living in modern day England. After surviving a plane crash, Gibreel Farishta, a Bollywood superstar is left to rebuild his life, while the other survivor, the emigrant Saladin Chamcha has his life torn apart.

Why was it banned? Many in the Islamic community saw Rushdie’s take on Islam to be blasphemous. In Venezuela, you would be imprisoned for 15 months if caught reading the book, while Japan issued fines for people who sold the English-language edition. Even in the US, two major bookshops refused to sell the book after death threats were received.

The Perks of Being a Wallflower by Stephen Chobsky (1999)

6. THE PERKS OF BEING A WALLFLOWER BY STEPHEN CHOBSKY (1999)

The gist: Inspired by the late J. D. Salinger’s The Catcher in the Rye, the book, published in 1999, tells the story of a teenager, “Charlie” who writes a series of letters to an anonymous friend. Being a teenager, Charlie goes to great lengths to describe his introversion, teenage sexuality, abuse, and his drug use.

Why was it banned? Its explicit sexual content, particularly the homosexual aspects, has led it to be withdrawn from libraries across the US, and it regularly makes the American Library Association’s top 10 most challenged books list.

Things Fall Apart by Chinua Achebe (1958)

7. THINGS FALL APART BY CHINUA ACHEBE (1958)

The gist: One of the most celebrated pieces of African literature, Achebe’s story of Okonkwo, a leader and local wrestling champion in Umofia – a fictional group of nine villages in Nigeria – recalls the influences of British colonialism and Christian missionaries on his traditional Igbo community during an unspecified time period in the late nineteenth or early twentieth century.

Why was it banned? Reportedly banned in Malaysia, it is critical of colonialism and its consequences.

American Psycho by Brett Easton Ellis (1991)

8. AMERICAN PSYCHO BY BRETT EASTON ELLIS (1991)

The gist: Easton Ellis’s tale of serial killer and impeccable business man Patrick Bateman, starts off as merely the retelling of one man’s experiences living in an affluent part of New York city during the 1980s. As the book progresses however, the shiny veneer of Yuppie life soon reveals a far more sinister side.

Why is it banned? Anyone who has seen the film will know why. Germany deemed it harmful to minors when it first appeared in 1991, and restricted its sales. It was banned in Canada until very recently, and it’s banned in the Australian state of Queensland and is restricted to over 18s only in all other states.

The Metamorphosis by Franz Kafka (1915)

9. THE METAMORPHOSIS BY FRANZ KAFKA (1915)

The gist: One day, Gregor Samsa, a travelling salesman supporting his parents and sister, awakes to find he’s turned into a giant bug. Once the most beloved member of his family, so begins his estrangement from his beloved, and the rest of society, to the point where he is locked away in his room and plainly forgotten about.

Why was it banned? All of Kafka’s work was banned under the Nazi and Soviet regimes, and also in Czechoslovakia because he refused to write in Czech, using only German.

10. LOLITA BY VLADIMIR NABOKOV (1955)

The gist: Humbert Humbert, a scholar born in Paris, is obsessed with young women, or “nymphets” as he calls them. Moving to a small New England town, he comes obsessed with the 12-year-old daughter of Charlotte Haze, and secretly covets her, using his marriage to her mother as a ruse. Humbert and the girl abscond and begin hopping from town to town trying to conceal their true relationship.

Why was it banned? After being called ‘the filthiest book I have ever read’ by the editor of the Sunday Express, the Home Office seized all copies of the book in 1955 on the grounds that it was pornography. The French banned it the following year, but curiously, it was published without issue in the USA.

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