Web inventor says Internet should be ‘human right’


Tim Berners-Lee said on Thursday the Internet can help tackle inequality but only if it comes with the rights to privacy and freedom of expression.

The computer scientist credited with inventing the World Wide Web says affordable access to the Internet should be recognized as a human right, as a report showed that billions of people still cannot go online and government surveillance and censorship are increasing.

Tim Berners-Lee, the British scientist credited with inventing the World Wide Web, says affordable access to the Internet should be recognized as a human right. File photo

Tim Berners-Lee said on Thursday the Internet can help tackle inequality but only if it comes with the rights to privacy and freedom of expression. The Briton, who launched the Web in 1990, made the remarks as he released his World Wide Web Foundation’s latest report tracking the Internet’s global impact.

The Web Index found that laws preventing mass online surveillance are weak or nonexistent in more than 84 percent of countries. It also said that almost 40 percent of surveyed countries were blocking sensitive online content to a “moderate or extreme degree,” and that half of all Web users live in countries that severely restrict their rights online.

Almost 4.4 billion people most of them in developing countries still have no access to the Internet, the Web Index said.

“It’s time to recognize the Internet as a basic human right,” Mr. Berners-Lee said. “That means guaranteeing affordable access for all, ensuring Internet packets are delivered without commercial or political discrimination, and protecting the privacy and freedom of Web users regardless of where they live.”

Denmark, Finland, and Norway were ranked as top overall, meaning they were best at using the Internet for economic, political and social progress. At the bottom of a list of 86 countries were Yemen, Myanmar and Ethiopia.

Mr. Berners-Lee was working an engineer at the CERN laboratory in Geneva when he proposed the idea of a World Wide Web in 1989.

 

 

The $6.5m canyon: it’s the most expensive photograph ever – but it’s like a hackneyed poster in a posh hotel .


The $6.5m canyon: it’s the most expensive photograph ever – but it’s like a hackneyed poster in a posh hotel
Peter Lik’s hollow, cliched and tasteless black and white shot of an Arizona canyon isn’t art – and proves that photography never will be.

Phantom
Counterpoint: Photography is art and always will be

‘Beauty is cheap if you point a camera at a grand phenomenon of nature’ … Phantom. Photograph: Peter Lik
Jonathan Jones

Photography is not an art. It is a technology. We have no excuse to ignore this obvious fact in the age of digital cameras, when the most beguiling high-definition images and effects are available to millions. My iPad can take panoramic views that are gorgeous to look at. Does that make me an artist? No, it just makes my tablet one hell of a device.

The news that landscape photographer Peter Lik has sold his picture Phantom for $6.5m (£4.1m), setting a new record for the most expensive photograph of all time, will be widely taken as proof to the contrary. In our world where money talks, the absurd inflated price that has been paid by some fool for this “fine art photograph” will be hailed as proof that photography has arrived as art.

Yet a closer look at Phantom reveals exactly the opposite. This record-setting picture typifies everything that goes wrong when photographers think they are artists. It is derivative, sentimental in its studied romanticism, and consequently in very poor taste. It looks like a posh poster you might find framed in a pretentious hotel room.

Phantom is a black-and-white shot taken in Antelope Canyon, Arizona. The fact that it is in black and white should give us pause. Today, this deliberate use of an outmoded style can only be nostalgic and affected, an “arty” special effect. We’ve all got that option in our photography software. Yeah, my pics of the Parthenon this summer looked really awesome in monochrome.

Lik’s photograph is of course beautiful in a slick way, but beauty is cheap if you point a camera at a grand phenomenon of nature. The monochrome detailing of the canyon is sculptural enough, and a shaft of sunlight penetrating its depths becomes the phantom of the title. Yet, in fact, this downward stream of light is simply a natural aspect of Antelope Canyon. Look it up online and you will find a vast range of photographs that all show the same feature. They are all just as striking as Phantom. The photographer has added nothing of any value to what was there already. Google is full of “great” pictures of this awe-inspiring natural feature.

Someone has been very foolish with their money, mistaking the picturesque for high art.

As a colour picture without any arty claims, this would be a valuable record of nature. Instead, it claims to be more than that; it aspires to be “art”. It is this ostentatious artfulness that pushes it into the realm of the false. For the artistic ambition of this picture is so very derivative from paintings that were created more than a century ago. Just like the very first “art” photographers in the Victorian age, Lik apes the classics in order to seem classic.

Phantom aims for the sublime, that sense of awe in front of nature that was described by Edmund Burke in the 18th century and taken to lavish heights by painters in the 19th. American painters especially, such as Frederic Edwin Church and Albert Bierstadt, used a heightened romantic style to express the grandeur and amazement of the American landscape. Later, Georgia O’Keeffe added a surreal dreaminess to the west’s iconography. Film-makers, above all John Ford, were influenced by the American landscape painters when they put the west on screen.

Phantom comes along in the wake of all these representations of the American landscape in art – and lazily emulates them. It is a cliche: easy on the eye, easy on the brain, hackneyed and third-hand.

If this is the most valuable “fine art photograph” in history, God help fine art photography. For this hollow and overblown creation exposes the illusion that lures us all, when we’re having a good day with a good camera – the fantasy that taking a picture is the same thing as making a work of art

Staying healthy and surviving our toxic world


There’s no question our bodies were not meant to battle the number of toxins we are now exposed to each day. The rise in cancer rates is enough of a barometer to incite fear. We can also find warning in the rise of asthma, autism, ADHD, dementias, and auto-immune diseases. So how do we survive, and better yet, achieve optimal health?

organic

What to eat in a toxic world

First and foremost, eat organic whenever possible. This is such a no-brainer. Why would you want to add herbicides, fungicides, and pesticides to your body?

If you eat meat or dairy, remember you are eating on top of the food chain. Organic is vitally important for meat and dairy foods. If you eat conventional, you are exposing yourself to all of the toxins that animal has accumulated, which include those above plus GMOs, antibiotics, and hormones.

Do not ingest artificial chemicals. In other words, do not eat any food with artificial flavorings, colorings, or preservatives. No BHA, BHT, MSG, GMOs, or trans fats. And if you want your immune system to work right, stay away from processed sugar – all processed sugars. The bottom line is this: eat real food – unprocessed, fresh, organic, whole, nutrient dense food. The best possible diet is for 80% or more of your diet to consist of raw produce, more vegetables than fruit.

Drink clean water -distilled or spring water is best. At the very least, filter your water.

Diet is the most important factor in our survival – it is the basis of good health. Even in a cesspool of environmental toxicity (Okinawa) a good diet results in low cancer rates. Yet these same people immigrate to the United States, adopt a Western diet, and their cancer rates mirror our own.

How to cook and store food

Don’t use a microwave and never cook in aluminum. Don’t use non-stick bakeware of any kind. There is a new breed of non-stick pots and pans, but why risk it? Use cast iron, glass, enamel, ceramic, and stainless steel. Cast iron is the original non-stick pan. If you season it right, cast iron is always easy to clean. Even if food is glued to it, a ten-minute soak in hot water is all it takes to completely loosen the food. A quick scrub and it’s clean.

Don’t cook with high heat, and don’t cook quickly unless you’re boiling, steaming, or using a pressure cooker.

Cook with whole herbs that have superfood qualities like turmeric, ginger, garlic, onions, and oregano.

Don’t cook so often. Prepare raw meals and eat lots of raw produce and big salad with the aforementioned herbs.

Store leftovers in glass, not plastic. Chemicals from plastics leach into food. And do your best to avoid buying food in plastic containers. Again, whole foods avoid the packaging issue so common to processed foods.

Don’t pollute your environment

Whenever possible, surround yourself with non-toxic furnishings, carpeting, paints, etc. But since we can’t always take control of what’s already built in to our environment, the least we can do is avoid adding to our home’s toxic load. Use natural cleaners like vinegar, baking soda, and lemons or purchase toxic free cleaners. Do not use air fresheners. If necessary, use essential oils or boil citrus peels on the stove to freshen the air.

Don’t add toxins to your body through your skin

Our skin absorbs any and everything we put on it. So choose organic skin products – soaps, shampoos, conditioners, shaving cream, lotions, and make-up. Use oils for lotions (like coconut oil or almond oil).

Kill Candida and detox at least twice a year

A bi-annual detox is a necessity, even when you are living as clean a life as possible. There are just too many toxins in the food, water, and air to miss this opportunity to cleanse the body. For more on detoxification, check out Balance Your Eco-system and The Cheap and Easy Detox.

Sources:

http://www.organiclifestylemagazine.com

http://www.organiclifestylemagazine.com

http://www.organiclifestylemagazine.com

http://www.naturalnews.com

http://www.organiclifestylemagazine.com

http://truthwiki.org/Garlic

http://truthwiki.org/Oregano

Learn more: http://www.naturalnews.com/047926_toxic_environment_detoxification_healthy_cooking.html#ixzz3LnK6nBLt

Immunotherapy Drug Pembrolizumab Safe for Patients With Triple-negative Breast Cancer, Effective in Some


A phase Ib clinical trial to evaluate the efficacy and tolerability of  pembrolizumab in patients with metastatic triple-negative breast cancer showed the drug was well tolerated and yielded durable responses, according to data presented at the 2014 San Antonio Breast Cancer Symposium, held Dec. 9–13.

“We observed that 18.5 percent of patients with PD-L1 expressing triple-negative breast tumors had a response to therapy,” said Rita Nanda, MD, assistant professor of medicine and associate director of the Breast Medical Oncology Program at the University of Chicago. “Pembrolizumab therapy was well tolerated, with a manageable side effect profile.” For those patients who responded to therapy, responses were quite durable, and median duration of response was not yet reached at the time of presentation.

“Currently, there are no approved targeted therapies to treat metastatic triple-negative breast cancer (TNBC), and the median survival for patients with this disease is approximately one year,” Nanda added. “The promising activity of pembrolizumab seen in PD-L1-expressing triple-negative breast cancer is very exciting, and certainly worthy of further investigation.”

Nanda and colleagues recruited 32 patients to this multicenter, nonrandomized trial. Patients were aged 29 to 72 years, and had metastatic TNBC that had either relapsed after treatment for early-stage disease or progressed on therapy for advanced disease. All patients received intravenous infusions of 10 mg per kg of pembrolizumab every two weeks.

Primary endpoints of this study were to determine the safety, tolerability, and antitumor activity of pembrolizumab.

Five patients experienced at least one grade 3 to grade 5 drug-related adverse event, with one patient experiencing a grade 5 event.

Upon central review, of the 27 patients with measurable disease for best overall response, one patient had a complete response (CR), four had a partial response (PR), seven had stable disease, and 12 had progressive disease. In addition, three patients discontinued therapy prior to the first post-baseline scan due to clinical progression. At the time of this presentation, one patient with a CR and two patients with a PR continue to be treated with pembrolizumab.

Left-Handed People Make Less Money Than Righties


It pays to be right-handed.

According to a recent study published in the Journal of Economic Perspectives, lefties make about 10 to 12 percent less annually than righties. The paper, written by Joshua Goodman, an economist at Harvard’s Kennedy School, is the first study to document the income gap between right-handed and left-handed people.

Why the gap? It may have something to do with how left-handedness correlates with other attributes. Goodman found that left-handed people “have more emotional and behavioral problems, have more learning disabilities such as dyslexia, complete less schooling, and work in occupations requiring less cognitive skill.”

One interesting exception, however, is that lefties born to left-handed mothers don’t tend to show lower cognitive abilities than righties.

In his research, Goodman analyzed five data sets from the U.S. and the U.K. that all look at how handedness affects cognitive skill and income over a set amount of time. Goodman found that about 11 to 13 percent of the population is left-handed, a finding that prior research supports.

Lefties have historically been marginalized by society. As Goodman points out, during the Middle Ages, left-handed people were “thought to be possessed by the devil.” The medieval Jewish philosopher Maimonides said that lefties shouldn’t become priests. In 1903, the Italian criminologist Cesare Lombroso wrote, “What is sure… is, that criminals are more often left-handed than honest men, and lunatics are more sensitively left-sided than either of the other two.”

Even the word “left” itself has unpleasant connotations, if you go back to its roots. It’s a derivation of the Old English word “lyft,” which meant “idle, weak, or useless,” according to Goodman’s paper.

But today, “left-handedness has come into vogue,” Goodman points out, “with modern proponents who argue that left-handedness is overrepresented among highly talented individuals.”

After all, three out of the last four presidents have been left-handed, with George W. Bush being the only righty of the group. A bunch of successful people, like Bill Gates and Oprah Winfrey, are also lefties. And there’s new research suggesting that left-handed people may be more creative.

There are at least two widely cited studies that suggest there is a greater share of lefties among smart people. A study from 1986 found that lefties are more prevalent among students who got top scores on the SAT, while a study from 1980 found that there was a higher percentage of lefties among gifted elementary school students than among their non-gifted peers.

Goodman’s study seems to fly in the face of that. But as Peter Orszag recently pointed out at Bloomberg View, Goodman’s research doesn’t necessarily debunk the earlier findings.

Orszag wrote:

It is still possible that lefties are disproportionately represented among the very top of the skills distribution; the databases Goodman uses don’t contain enough detail about these extremes to say either way. The SAT study, for example, examined those in the top 1 out of 10,000, and IQs above 131 are found only in the top 2 percent of the population.

  LEFT HAND

In other words, among the successful crowd, being left-handed might correlate with certain advantages. But among the rest of us, statistically, it’s righties who come out on to

New approaches to treating depression .


A young woman sits curled up on her bed, her head in her hands.For years depression has been seen as a biological condition, with medication a commonly recommended treatment. However drugs don’t suit everyone and now researchers are trying a range of different approaches to treat depression, from clinical hypnosis to brain stimulation. Lynne Malcolm reports.

 

Depression is the most common mental health disorder in Australia, affecting around one million people nationally, and is a major contributor to the global burden of disease.

What we’ve discovered … is that the drugs have not been nearly as effective as people had been led to believe.

MICHAEL YAPKO, CLINICAL PSYCHOLOGIST

Chrissie, who is now in her 30s, began her struggle with depression when she was a teenager. At the time, her family was grieving over the death of her father, so her condition was not immediately acknowledged.

‘It just kind of turned into this ongoing, untreated issue for me which would come and go,’ she recalls. ‘In my kind of blind way I stumbled through lots of different attempts to sort it out. And when it would go, I’d think, “Okay, now I am a better and I don’t [need to] think about that anymore.” But there was this sort of dread that it would come back.’

Over the years she tried meditation and various forms of counselling, but it wasn’t until after the birth of her first child that anti-depressant medication was suggested. While this helped her get on with her life for a few years, she remembers feeling very flat emotionally.

‘I didn’t laugh. I just went through life like a machine,’ she says.

Chrissie decided to stop taking the medication and another big bout of depression followed—at the same time her marriage fell apart and her mother suffered a major stroke.

‘This is a condition that will play out over a long period of time. It’s not like a cold where the symptoms are sudden, you feel them, you know that you are subjected to this particular illness,’ she says.

‘It can be so vague … I guess people who have very extreme depression can’t get up and they can’t dress … for me I might have a day every now and again like that but that wouldn’t be every day. But still, every day is a struggle. So I’m just trying to swim and muddle through my life during these periods, and it makes it really tough.’

Whilst many people are helped by anti-depressant medication, the treatment doesn’t suit a significant proportion of people, either because it is ineffective or the side effects are too unpleasant.  Now, researchers and clinicians are exploring alternative approaches to treatment.

Clinical psychologist Michael Yapko from San Diego, California, suggests that a serious revision of people’s attitudes towards depression is now required, because while people focus on the biology of depression, they miss what goes on at the psychological and social levels.

‘Most depression experts have really stopped talking about the biochemical imbalance and certainly the shortage of serotonin and have started looking at other neurological factors, what are called trophic factors that increase certain proteins,’ Yapko says.

‘But what we’ve discovered, of course, is that the drugs have not been nearly as effective as people had been led to believe. The major medical journals have been publishing article after article about the deceptions of the pharmaceutical industry in deliberately overstating their value in order to sell them. And trying to define depression as a medical illness has really backfired.’

Yapko has been using clinical hypnosis as an effective therapeutic tool for the treatment of depression for many years.

‘What happens in depression is that people tend to focus on what’s wrong instead of what’s right, what has hurt them instead of what has helped them. They focus on things that work against them. Hypnosis is a focusing process … an efficient way of securing somebody’s attention … in the direction of focusing on what is positive, what’s useful,’ he says.

‘It encourages a greater flexibility, a greater willingness to have experiences that go beyond just feelings or just rationality and give people a chance to connect with and develop parts of themselves that are the best parts of themselves.’

Yapko says that there’s now a large body of research which shows the success rates of various depression treatments.

‘There are a number of psychotherapies, cognitive behavioural therapy and interpersonal therapy in particular that have the highest treatment success rates. Cognitive therapy teaches people skills. It helps people with information processing, clearer thinking, and better quality of decision making,’ he says.

‘Interpersonal therapy focuses on the social side, the relationships. Given how often relationship issues lead people into depression—divorces, betrayals, abuses, violence, all the kinds of things that can happen in relationships that lead people into depression—the interpersonal model really focuses on teaching social skills and helping people build more positive and healthier relationships.’

Yapko says it’s also clear that the more actively people are engaged in their treatment, the better they do, and just taking medication alone has the highest rate of relapse of any form of treatment.

Whilst some clinicians are concerned that cultural and social factors have too often been overlooked in past treatments, other researchers are investigating the potential of using techniques based in neuroscience, like brain stimulation.

Professor Colleen Loo from the school of psychiatry at the University of New South Wales and the Black Dog Institute leads a research team investigating transcranial direct current stimulation, or TDCS.

TDCS uses a tiny electrical current, about one 500th of the current that is used in the better known Electro Convulsive Therapy or ECT. TDCS is non-invasive and it gently stimulates the surface of the brain, via electrodes which are placed either side of the forehead.

It’s understood that when people are depressed the frontal part of the brain is under-active, and at the same time there is overactivity in other parts of the brain, such as the areas involved in emotion. Loo says that TDCS can correct this imbalance of activity.

‘It’s exciting because what some of the emerging evidence is starting to show is that effective treatments affect the whole connection, the functional connectivity between these different parts of the brain. So it kind of restores the balance between these different parts of the brain,’ Loo says.

So far the clinical trials of TDCS are looking good for the treatment of depression in people who haven’t responded well to other treatments. Loo says that there are very few, if any, side-effects and some participants have even noticed benefits beyond changes to their moods.

‘We were very excited when we got to the end of the study and we formally analysed the results of the test … it showed exactly what people were saying to us, that after the act of stimulation the actual thinking speed was faster, and that has led our team to develop a whole parallel line of research of using TDCS to improve memory and thinking.’

TDCS treatment is not yet available outside of research trials, but Loo sees promising potential for it in the future.

Chrissie, who has suffered from depression for many years, has been in the TDCS program at the Black Dog Institute since the beginning of this year. She feels that her symptoms of depression have significantly improved.

‘Well, I can function, I feel quite normal. My mood swings and my highs and my lows are manageable … I’m not overtaken by this tide of negative emotion. I think negative emotion is really natural and normal, but in depression it just gets really out of balance,’ she says.

‘The trial has been really great for that. It’s the treatment itself but at the same time every time I go in I have to evaluate my emotion. In a sense there has been this kind of therapeutic response to that too because I now just habitually go—well, how am I today? I’m just a bit more aware of my vulnerability and the imbalances that I can have.

‘It’s such a funny beast, depression, it can really trick you and you can trick it. It’s like flicking switches sometimes, [it’s] very strange.’

New anti-obesity drug can cut body weight by 30% .


A new anti-obesity drug has been developed that can cut excess weight by a third, and has cured lab animals of obesity and diabetes.

Researchers in Germany have developed a new drug that combines the actions of three gastrointestinal hormones to improve glucose sensitivity and calorie burning, while reducing appetite. And in pre-clinical trials with mice, it reduced their body weight by 30 percent.

The development of the drug was based on previous work showing that chemical compounds called peptides that have been engineered to influence the activity of gastrointestinal hormones can effectively treat adult-onset diabetes. Named GLP-1 and GIP, these two hormones are released by the body after you eat, so blood sugar levels can remain stable. GLP-1 is also responsible for curbing feelings of hunger when you’re full. A disruption of these hormones – experienced in people with type 2 diabetes – can lead to hypoglycaemia.

Expanding on that research, the team from Helmholtz Diabetes Centre in Germany has added another hormone to the mix – glucagon, which act very differently way to the other two hormones. It’s glucagon’s job to raise blood sugar levels by signalling the liver to convert fat into sugar, says Nsikan Akpan at Science Magazine. “As hyperglycaemia progresses in diabetes, the body shuts the hormone off in a presumed attempt to restore sugar balance, but that also stymies fat burning. In normal people and bariatric surgery patients, glucagon lowers fat and can trigger weight loss,” she says.

“This triple hormone effect in a single molecule shows results never achieved before,” one of the team, biochemist Brian Finan, said in a press release. “A number of metabolic control centres are influenced simultaneously, namely in the pancreas, liver, fat depots, and brain.”

When lab mice were treated with the new drug over a three-week period, their body weight dropped by a third, and their blood glucose levels were halved. According to Akpan, the fat mass was also reduced by a third, on average, but healthy lean mass was left alone. The results were published in Nature Medicine.

“Think of this as an injectable elixir that could reverse obesity and type 2 diabetes by cheating a body into believing that it just received a gastric bypass,” said one of the team, endocrinologist Matthias Tschöp, to Science Magazine

If they can get this drug ready for human trials, it could revolutionise how we treat obesity. It’s not just about dieting and exercising regularly, because once a person’s metabolism has been severely affected by high sugar and fat diets, their cells will be reprogrammed to act differently from the cells of a healthy person. This means obese people can’t lose weight in the same way that healthy, or even slightly overweight, people can.

Right now, obese people are given the treatment option of gastric bypass surgery – where sections of the intestines or stomach are removed to limit how much food the patient can each –  but it’s obviously an expensive and very invasive option. The hope is that drugs such as this new one will offer a way to force obesity-related hormones back into their regular, healthy routine in people affected by obesity.

Contact lens merges plastics and active electronics via 3-D printing


As part of a project demonstrating new 3-D printing techniques, Princeton researchers have embedded tiny light-emitting diodes into a standard contact lens, allowing the device to project beams of colored light.

Michael McAlpine, the lead researcher, cautioned that the lens is not designed for actual use—for one, it requires an external power supply. Instead, he said the team created the device to demonstrate the ability to “3-D print” electronics into complex shapes and materials.

“This shows that we can use 3-D printing to create complex electronics including semiconductors,” said McAlpine, an assistant professor of mechanical and aerospace engineering. “We were able to 3-D print an entire device, in this case an LED.”

The hard is made of plastic. The researchers used tiny crystals, called quantum dots, to create the LEDs that generated the colored light. Different size dots can be used to generate various colors.

“We used the quantum dots [also known as nanoparticles] as an ink,” McAlpine said. “We were able to generate two different colors, orange and green.”

The contact lens is also part of an ongoing effort to use 3-D printing to assemble diverse, and often hard-to-combine, materials into functioning devices. In the recent past, a team of Princeton professors including McAlpine created a bionic ear out of living cells with an embedded antenna that could receive radio signals.

Yong Lin Kong, a researcher on both projects, said the bionic ear presented a different type of challenge.

McAlpine and Yong Lin Kong, a graduate student in mechanical and aerospace engineering, use a custom-built 3-D printer to create the electronics described in their research. Credit: Frank Wojciechowski

“The main focus of the project was to demonstrate the merger of electronics and biological materials,” said Kong, a graduate student in mechanical and aerospace engineering.

Kong, the lead author of the Oct. 31 article describing the current work in the journal Nano Letters, said that the contact lens project, on the other hand, involved the printing of active electronics using diverse materials. The materials were often mechanically, chemically or thermally incompatible—for example, using heat to shape one material could inadvertently destroy another material in close proximity. The team had to find ways to handle these incompatibilities and also had to develop new methods to print electronics, rather than use the techniques commonly used in the electronics industry.

“For example, it is not trivial to pattern a thin and uniform coating of nanoparticles and polymers without the involvement of conventional microfabrication techniques, yet the thickness and uniformity of the printed films are two of the critical parameters that determine the performance and yield of the printed active device,” Kong said.

To solve these interdisciplinary challenges, the researchers collaborated with Ian Tamargo, who graduated this year with a bachelor’s degree in chemistry; Hyoungsoo Kim, a postdoctoral research associate and fluid dynamics expert in the mechanical and aerospace engineering department; and Barry Rand, an assistant professor of electrical engineering and the Andlinger Center for Energy and the Environment.

McAlpine said that one of 3-D printing’s greatest strengths is its ability to create electronics in complex forms. Unlike traditional electronics manufacturing, which builds circuits in flat assemblies and then stacks them into three dimensions, 3-D printers can create vertical structures as easily as horizontal ones.

“In this case, we had a cube of LEDs,” he said. “Some of the wiring was vertical and some was horizontal.”

To conduct the research, the team built a new type of 3-D printer that McAlpine described as “somewhere between off-the-shelf and really fancy.” Dan Steingart, an assistant professor of mechanical and and the Andlinger Center, helped design and build the new printer, which McAlpine estimated cost in the neighborhood of $20,000.

McAlpine said that he does not envision 3-D printing replacing traditional manufacturing in electronics any time soon; instead, they are complementary technologies with very different strengths. Traditional manufacturing, which uses lithography to create electronic components, is a fast and efficient way to make multiple copies with a very high reliability. Manufacturers are using 3-D printing, which is slow but easy to change and customize, to create molds and patterns for rapid prototyping.

Prime uses for 3-D printing are situations that demand flexibility and that need to be tailored to a specific use. For example, conventional manufacturing techniques are not practical for medical devices that need to be fit to a patient’s particular shape or devices that require the blending of unusual materials in customized ways.

“Trying to print a cellphone is probably not the way to go,” McAlpine said. “It is customization that gives the power to 3-D printing.”

In this case, the researchers were able to custom 3-D print electronics on a contact lens by first scanning the lens, and feeding the geometric information back into the printer. This allowed for conformal 3-D printing of an LED on the contact lens.

11 Reasons Dehydration Is Making You Sick And Fat


11-reasonnnsss-1050x603 Adverse effects from not drinking enough water include digestive, skin, bladder and kidney problems, fatigue, and even headaches. We need water as much as the air we breathe in! Keeping your body hydrated is not a joke.

Did you know that dehydration actually sets in just before you start feeling thirsty? Sipping water throughout the day is the best way to handle it. Always have a bottle or a glass of water handy! If you’re not a morning person, having two glasses of water right after you wake up will boost up your blood pressure to normal levels, and it’s way healthier than having your first coffee on an empty stomach.

Many of us believe that merely drinking fluids like sweetened juices, soda or tea will hydrate you as well as waterdoes. This is not true. It’s actually the opposite! To deal with the excess sugar and salt you are taking in your body wastes immense amounts of precious water just to clean it out from your system. And if you love your coffee, make sure to drink one extra glass of water for every cup you have.

Drinking water regularly speeds up your metabolism and makes you feel more ‘full’. You will eat less once you start drinking more! It’s the safest and healthiest way to lose weight. Drink up!

dehaydration

Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients With Noncancer Pain


Importance  Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia.

Objective  To assess whether tramadol use, when compared with codeine use, is associated with an increased risk of hospitalization for hypoglycemia.

Design, Setting, and Participants  A nested case-control analysis was conducted within the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database of all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012. Cohort and case-crossover analyses were also conducted to assess consistency of the results.

Main Outcomes and Measures  Cases of hospitalization for hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated comparing use of tramadol with codeine. A cohort analysis, with high-dimensional propensity score–adjusted hazard ratios (HRs) and 95% CIs, was performed comparing tramadol with codeine in the first 30 days after treatment initiation. Finally, a case-crossover analysis was also performed, in which exposure to tramadol in a 30-day risk period immediately before the hospitalization for hypoglycemia was compared with 11 consecutive 30-day control periods. Odds ratios and 95% CIs were estimated using conditional logistic regression analysis.

Results  The cohort included 334 034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11 019 controls. Compared with codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (OR, 1.52 [95% CI, 1.09-2.10]), particularly elevated in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the cohort (HR, 3.60 [95% CI, 1.56-8.34]) and case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]).

Conclusions and Relevance  The initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.

INTRODUCTION

Tramadol hydrochloride is a weak opioid analgesic whose use has increased steadily worldwide.1,2Recently, several spontaneous reports have raised concerns that its use might be associated with an increased risk of hypoglycemia.3– 8 In a pharmacovigilance study, tramadol-induced hypoglycemia occurred rapidly after initiation—within 10 days of treatment.8 Moreover, there were no known risk factors, such as diabetes mellitus, in more than 40% of the reports.8

Hypoglycemia is a serious clinical event that has been associated with elevated death rates in patients with diabetes.9– 11 Furthermore, prolonged and profound hypoglycemia can cause brain death, as well as fatal cardiac arrhythmia.12 With respect to tramadol, it is biologically plausible that it may induce hypoglycemia through its dual effects on μ opioid receptors and inhibitory activity on serotonin-norepinephrine reuptake.13

Given the increasing use of tramadol in the general population,1,2 there is a need to assess whether this drug is associated with an increased risk of hospitalization for hypoglycemia, a potentially fatal outcome. The objective of this large population-based study was to determine whether use of tramadol, when compared with use of codeine, another weak opioid not previously associated with hypoglycemia, is associated with an increased risk of hospitalization for hypoglycemia in individuals with noncancer pain.

METHODS

Data Sources

This study was conducted using the United Kingdom Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics (HES) database. The CPRD includes more than 13 million patients from more than 680 practices in the United Kingdom14 and records information on diagnoses, prescriptions, referrals, lifestyle habits, and anthropometric measurements such as body mass index. Information in the CPRD is regularly audited and has been shown to be highly valid (median proportion of patients with confirmed diagnoses is 89%).15,16 Since 1997, the HES database records all hospitalizations in England. The recorded information includes hospitalization dates, primary and secondary diagnoses (coded using International Classification of Diseases, 10th Revision [ICD-10]), and related procedures.

The study protocol was approved by the Independent Scientific Advisory Committee of the CPRD (protocol 14_099R) and by the Research Ethics Board of Jewish General Hospital, Montreal, Quebec, Canada. Patient informed consent was not necessary since the data were anonymized for research purposes.

Study Population

We assembled a population-based cohort of patients newly treated with oral formulations of tramadol or codeine between April 1, 1998, and March 1, 2012. Patients initiating treatment with a codeine formulation for cough or diarrhea were not included. Cohort entry was defined by the date of the first prescription for these drugs during the study period. At cohort entry, patients were required to be at least 18 years old and have at least 1 year of baseline medical history in the CPRD and HES. We excluded patients concurrently prescribed other opioids at cohort entry (listed in eTable 1 in the Supplement), thus limiting the cohort to patients using tramadol or codeine only. We also excluded patients who had received a cancer diagnosis (other than nonmelanoma skin cancer) at any time before cohort entry, as well as those previously hospitalized for hypoglycemia (ICD-10codes E15, E16.0, E16.1, and E16.2, in primary or secondary position) in the year before cohort entry.

Patients were followed from cohort entry until the study outcome of hospitalization for hypoglycemia (defined in the Methods), death from any cause, end of registration with the general practice, or end of the study period (March 31, 2012), whichever occurred first.

Case-Control Selection

A nested case-control analysis was conducted within the aforementioned cohort. This analytic approach was chosen because of the time-varying nature of exposure, the size of the cohort, and the long duration of follow-up.17

Cases were all patients with a first hospitalization for hypoglycemia (recorded within the first 2 days of hospitalization; ICD-10 codes E15, E16.0, E16.1, or E16.2, in primary or secondary position) during the study period. The index date was defined as the time of the case’s hospital admission. Up to 10 controls were randomly selected from the risk sets of each case and matched on age, sex, and duration of follow-up.

Exposure Definition

Cases and controls were classified into 1 of 3 mutually exclusive categories on the basis of their exposure status at index date: (1) codeine use, defined by a first prescription in the 30 days before index date, with no prior prescriptions of codeine or tramadol in the year before the index date; (2) tramadol use, defined by a prescription in the 30 days before the index date, but no codeine prescriptions in the year before the index date; and (3) other patterns and combinations, consisting of concurrent use of tramadol and codeine, previous use of either tramadol or codeine in the year before the index date, and no use of either medication in the year before the index date. The tramadol group included those who initiated tramadol therapy 30 days or less before the index date, as well as those who initiated tramadol therapy more than 30 days before the index date. This was done to assess whether the risk varies with timing of treatment initiation, an analysis motivated by the pharmacovigilance study that signaled a rapid onset of tramadol-induced hypoglycemia (ie, within 10 days).8 Thus, in a secondary analysis, tramadol use was further classified according to timing of the first prescription in the year before the index date (ie, first prescription ≤30 days and >30 days before index date). The reference category for all analyses consisted of codeine use.

Potential Confounders

The following predefined baseline covariates were considered in the models: calendar year of cohort entry, body mass index, excessive alcohol use (defined as alcohol-related disorders such as alcoholism, alcoholic cirrhosis of the liver, alcoholic hepatitis, and hepatic failure), comorbidities (chronic renal insufficiency, liver disease, pancreatic disease, other endocrine disease [including adrenal insufficiency and hypopituitarism], and dumping syndrome–inducing surgical procedures [gastrectomy and bypass surgery]; all measured in the year before cohort entry), use of prescription drugs (antidiabetic drugs [insulins, sulfonylureas, metformin hydrochloride, other antidiabetic drugs; entered individually in the models], β-blockers, angiotensin-converting enzyme inhibitors, fluoroquinolones, co-trimoxazole, antiepileptics, antidepressants [selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, other antidepressants], antipsychotics, aspirin, nonsteroidal anti-inflammatory drugs, propoxyphene hydrochloride, and other opioids [listed in eTable 1 in the Supplement]; all measured in the 90 days before cohort entry), and opioid-related indications (headache, abdominal and pelvic pain, musculoskeletal pain, neuralgia, other pain [including chest pain, otolaryngological pain, and unspecified pain], injury or trauma, and surgery; all measured in the 90 days before cohort entry). As additional proxies of health status, the models also included the number of general practice visits and number of hospitalizations in the year before cohort entry, as well as number of prescription drugs received in the 90 days before cohort entry. Variables with missing data were coded with an “unknown” category.

Statistical Analysis
Primary Analysis: Nested Case-Control Approach

Descriptive statistics were used to summarize the characteristics of the cohort, cases and matched controls. We calculated the crude incidence of hospitalization for hypoglycemia, along with 95% confidence intervals (CIs) based on the Poisson distribution. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% CIs of hospitalization for hypoglycemia, comparing tramadol use with codeine use. We also conducted 2 secondary analyses. The first assessed the association with tramadol use, categorized according to timing of the first prescription before the index date (≤30 days and >30 days). The second assessed whether the presence of antidiabetic drug use at baseline modified the association between tramadol use and hospitalization for hypoglycemia. For this analysis, effect modification was assessed by including an interaction term between exposure status and the antidiabetic drug covariate. In addition to the matching factors (age, sex, and duration of follow-up) on which the logistic regression was conditioned, the models were adjusted for the aforementioned potential baseline confounders.

We conducted 3 sensitivity analyses to ascertain the robustness of the findings of the nested case-control analysis. In the first, the accuracy of the outcome definition was assessed by restricting the events to those coded in primary position. In the second and third analyses, we assessed whether hospitalizations for any cause in the 30 days before the index date, and surgical procedures in the 90 days before the index date, were effect modifiers. Effect modification was assessed by including interaction terms in the model.

Secondary Analysis: Cohort Approach Among First-Time Users

By design, the nested case-control analysis may have included reinitiators of tramadol and codeine use—patients who may have used these agents in the past but did not experience hypoglycemia. The inclusion of such “survivors” may lead to an overall underestimation of the risk through the depletion of susceptibles phenomenon.18 Furthermore, because of the relatively long follow-up, adjustment for baseline covariates may introduce residual confounding given that they may no longer optimally predict future exposure and outcome. Thus, to address these concerns, we conducted a cohort analysis restricted to first-time tramadol and codeine users (ie, patients identified at cohort entry). These patients were observed for a maximum of 30 days or until a hospitalization for hypoglycemia (as defined in the Methods), a hospitalization unrelated to hypoglycemia, death from any cause, end of registration with the general practice, or end of the study period (March 31, 2012), whichever occurred first.

Kaplan-Meier curves were plotted to compare the cumulative incidence of hospitalization for hypoglycemia of tramadol use with that of codeine use up to 30 days after treatment initiation. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios with 95% CIs of hospitalization for hypoglycemia associated with tramadol use compared with codeine. The model was adjusted for high-dimensional propensity score (HD-PS) quartiles,19 which were calculated using multivariate logistic regression analysis as the probability of being exposed to tramadol vs codeine, conditional on the aforementioned 41 predefined baseline covariates and 500 empirically defined covariates from 7 data dimensions (additional information on this approach is provided in eMethods 1 in the Supplement). Overall, there was excellent overlap between the propensity score distributions, with a c-statistic of 0.69. The proportionality assumption of the Cox model was met and ascertained on the basis of Schoenfeld residuals.

Secondary Analysis: Case-Crossover Approach

As a means to address residual confounding, we also conducted a case-crossover analysis in which cases serve as their own controls. This method implicitly controls for all known and unknown time-independent confounders and can be used to investigate associations between transient exposures and acute outcome events.20

In this analysis, we used the same cases that were identified for the nested case-control approach. For each of these cases, we subdivided the year prior to the index date into 12 consecutive 30-day periods, with a risk period immediately prior to the index date, and 11 control periods (eFigure 1 in the Supplement). Thus, exposure to tramadol in the 30-day risk period prior to the hospitalization for hypoglycemia was compared with that of the 11 previous consecutive 30-day control periods. Because tramadol can be used over the long term by some patients (which can affect the precision of the point estimate by affecting the number of discordant pairs on which the analysis is based), the case series was restricted to those with fewer than 6 exposed control periods, an exposure distribution that corresponds more closely to a transient exposure.21

We conducted an additional analysis to assess whether tramadol use is associated with an increased risk of fatal hypoglycemia, defined as an in-hospital death following a hypoglycemia-related hospitalization. For this analysis, the cases with such in-hospital deaths were similarly restricted to those who transiently used tramadol (<6 exposed control periods). For both hypoglycemia hospitalization and fatal hypoglycemia, conditional logistic regression analysis was used to estimate ORs with 95% CIs comparing exposure in a 30-day risk period immediately before the hospitalization for hypoglycemia with that of 11 previous 30-day consecutive control periods. Overall, there was no evidence of an exposure time-trend in the year before the event date, thus satisfying one of the key assumptions of this approach (additional information regarding the assessment of the exposure time-trend can be found in eMethods 2 in the Supplement).22 All analyses described here were performed using SAS, version 9.3 (SAS Institute Inc).

RESULTS

A total of 334 034 patients met the study cohort inclusion criteria, which included 28 110 and 305 924 new users of tramadol and codeine, respectively (eFigure 2 in the Supplement). The use of tramadol increased more than 8-fold during the study period, from 25 334 prescriptions in 1999 to 215 709 prescriptions in 2011 (Figure 1). Overall, tramadol and codeine users were similar with respect to age, sex, comorbidities, and prescription drug use, including antidiabetic drugs. In contrast, tramadol users were more likely to have undergone surgery in the 90 days before cohort entry (eTable 2 in the Supplement).

Figure 1.
Prescribing Trends of Tramadol Hydrochloride in the United Kingdom Clinical Practice Research Datalink Between 1999 and 2011
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Primary Analysis: Nested Case-Control Approach

During a mean follow-up of 5.0 years, generating 1 680 000 person-years, there were a total 1105 cases of hospitalization for hypoglycemia (crude incidence, 0.7 [95% CI, 0.6-0.7] per 1000 person-years) in the entire cohort. Of these, 112 (10.1%) were fatal. Table 1 presents the baseline characteristics of the 1105 cases and 11 019 matched controls. Compared with matched controls, cases were less likely to have ever smoked, but more likely to be obese and less healthy, in terms of comorbidities and prescription drug use.

Table 1.  Baseline Characteristics of Cases Hospitalized for Hypoglycemia and Matched Controls of the Primary Nested Case-Control Approach

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Table 2 presents the results of the primary nested case-control approach. Compared with codeine use, tramadol use was associated with a 52% increased risk of hospitalization for hypoglycemia (adjusted OR, 1.52 [95% CI, 1.09-2.10]). In a secondary analysis, the risk was highest in patients who initiated the treatment within 30 days of the index date (adjusted OR, 2.61 [95% CI, 1.61-4.23]), whereas the OR was closer to the null in users who initiated the treatment more than 30 days before the index date (adjusted OR, 1.17 [95% CI, 0.78-1.75]). Finally, the presence of antidiabetic drug use modified the association between tramadol use and hypoglycemia. Specifically, the OR was higher in nonusers than in users of antidiabetic drugs (adjusted OR, 2.12 [95% CI, 1.18-3.79] vs 1.11 [95% CI, 0.76-1.64], respectively; P for interaction = .02).

Table 2.  Crude and Adjusted Odds Ratios of Hospitalization for Hypoglycemia Comparing Use of Tramadol With Codeine in the Primary Nested Case-Control Approach

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There were 507 cases with a hospitalization for hypoglycemia coded in primary position. Restricting the analysis to these cases and their matched controls led to an increase in the OR compared with the primary analysis (adjusted OR, 2.15 [95% CI, 1.33-3.48]). The presence of hospitalizations in the 30 days before the index date did not statistically modify the association, although the OR was higher among patients with no hospitalizations (no hospitalizations: adjusted OR, 1.73 [95% CI, 1.15-2.61] vs hospitalization: adjusted OR, 0.98 [95% CI, 0.57-1.68]; P for interaction = .19). Similarly, there was no statistically significant effect modification by surgical procedures in the 90 days before the index date, although the OR was higher among those with no surgical procedures (no surgical procedures: adjusted OR, 1.66 [95% CI, 1.03-2.67] vs surgical procedures: adjusted OR, 1.11 [95% CI, 0.71-1.73]; P for interaction = .14).

Secondary Analysis: Cohort Approach Among First-Time Users

Overall, tramadol use was associated with a higher cumulative incidence of hospitalization for hypoglycemia than codeine use in the first 30 days after treatment initiation (log rank P < .001) (Figure 2). The crude incidences of hospitalization for hypoglycemia were 3.0 (95% CI, 1.3-6.0) and 0.7 (95% CI, 0.4-1.1) per 10 000 person-months in tramadol and codeine users, respectively. In the HD-PS–adjusted model, the initiation of tramadol use was associated with a more than 3-fold increased risk of hospitalization for hypoglycemia, compared with codeine use (HD-PS–adjusted HR, 3.60 [95% CI, 1.56-8.34]) (eTable 3 in the Supplement).

Figure 2.
Cumulative Incidence of Hospitalization for Hypoglycemia in Patients Newly Treated With Tramadol Hydrochloride and Codeine in the First 30 Days After Treatment Initiation
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Secondary Analysis: Case-Crossover Approach

Among the 1105 cases hospitalized for hypoglycemia during the study period, 176 had received at least 1 prescription in the year before the index date, 141 (80.1%) of whom used tramadol transiently (eFigure 3 in the Supplement). Overall, transient tramadol use was associated with an increased risk of hospitalization for hypoglycemia (exposed risk vs control periods: 36.9% vs 13.2%; OR, 3.80 [95% CI, 2.64-5.47]). Transient tramadol use was also associated with an increased risk of fatal hypoglycemia (exposed risk vs control periods: 43.8% vs 9.7%; OR, 6.21 [95% CI, 2.23-17.26]).

DISCUSSION

To our knowledge, this is the first epidemiological study investigating the association between tramadol use and hospitalization for hypoglycemia. We found that tramadol use is associated with an increased risk of hospitalization for hypoglycemia, with the risk highest around the time of treatment initiation. These results were corroborated in cohort and case-crossover analyses, which also associated tramadol use with a more than 3-fold increased risk of hospitalization for hypoglycemia. Overall, these results remained robust in several secondary analyses, including among patients not using any antidiabetic drugs, as well as in sensitivity analyses.

The findings of this study confirm the reported signals of tramadol therapy potentially increasing the risk of hospitalization for hypoglycemia. Three recent case reports have described tramadol-induced hypoglycemia, which included patients with and without diabetes using the drug at the recommended doses.3,5,6 Hospitalization for hypoglycemia has also been reported in a woman with intentional tramadol overdose.7 An in-depth analysis of spontaneous reports from a French pharmacovigilance database identified 43 tramadol-associated hypoglycemia cases between 1997 and 2010.8 Most of these events occurred soon after initiation of tramadol therapy (77% within 10 days of treatment) and were more frequent in the elderly. Overall, our findings corroborate these signals because the increased risk seemed to be limited to the first 30 days of use and remained statistically significant in patients with no history of treated diabetes. The rarity of this outcome, approximately 7 per 10 000 per year, may explain why it was not observed in randomized clinical trials, which were underpowered to detect such events (a total of 1019 and 1378 tramadol-treated patients in osteoarthritis and lower back pain randomized clinical trials, respectively).23,24

The association between tramadol use and hypoglycemia is biologically plausible and may relate to its pharmacodynamic properties. Tramadol mainly acts through 2 mechanisms: the activation of µ opioid receptors and the inhibition of central serotonin and norepinephrine reuptake.13 Serotonin pathways are known to have complex effects on peripheral glucose regulation,25 with animal studies reporting that serotonin induces low glucose levels in diabetic mice and rats.26,27Moreover, use of antidepressants such as those acting through serotonin and norepinephrine reuptake inhibition has been previously associated with an increased risk of hypoglycemia.28,29 In addition to its effects on serotonin pathways, the activation of µ opioid receptors by tramadol may also increase the risk of hypoglycemia. In rats with streptozotocin-induced diabetes, a dose-dependent glucose-lowering effect was observed with tramadol.30 This effect persisted when these rats were depleted in serotonin with p-chlorophenylalanine, suggesting a serotonin-independent effect. Furthermore, this effect was weaker in rats previously treated with naloxone hydrochloride (a µ opioid receptor agonist), suggesting a strong implication of the µ pathways.30 Given the novelty of this association, these hypotheses remain speculative and will require additional investigation.

This study has several strengths. First, we assembled a large population-based cohort of patients initiating tramadol or codeine therapy. Second, the use of the CPRD and HES databases allowed us to control for a large number of potential confounders. Third, the use of a new-user design eliminated biases related to the inclusion of prevalent users.31 Fourth, confounding by indication was likely minimized by using codeine therapy as an active comparator. Indeed, tramadol and codeine users were similar on nearly all baseline potential confounders, likely owing to the fact that both agents have similar indications. Finally, we observed consistent results with the cohort and case-crossover approaches, which addressed concerns related to possible residual confounding.

This study has some limitations. First, CPRD prescriptions represent those written by general practitioners, and thus treatment adherence is unknown, although this misclassification tends to bias the point estimates toward the null hypothesis. Second, to our knowledge, HES-defined hypoglycemia has not been formally validated, although it has been used as an outcome in a previous unrelated study.32 However, similar results were obtained after the case definition was limited to those diagnoses in primary position. Third, because of the observational nature of the study, residual confounding needs to be considered. Reassuringly, we observed consistent results using different study design and analytic approaches (such as cohort analysis adjusted for HD-PS quartiles and case-crossover analysis). Moreover, it is important to note that, given the strong observed associations (point estimates ranging between 1.52 and 3.80), any unmeasured or unknown confounder would need to be strongly associated with both the exposure and outcome to completely confound the observed association. It is unclear whether such a confounder exists beyond those considered in the models. Finally, despite the large sample size, the rarity of the outcome led to wide confidence intervals in secondary analyses, and thus these should be interpreted with caution.

The initiation of tramadol use was significantly associated with a more than 2-fold increased risk of hospitalization for hypoglycemia, when compared with codeine use. Although rare, tramadol-induced hypoglycemia is a potentially fatal adverse event. The clinical significance of these novel findings requires additional investigation.

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