Single atom quantum dots created by researchers at Canada's National Institute for Nanotechnology and the University of Alberta make possible a new level of control over individual electrons, a development that suddenly brings quantum dot-based devices within reach.

Composed of a single atom of silicon and measuring less than one nanometre in diameter, these are the smallest quantum dots ever created.

Quantum dots have extraordinary electronic properties, like the ability to bottle-up normally slippery and speedy electrons, that allow controlled interactions among electrons to be put to use to do computations. Until now, quantum dots have been useable only at impractically low temperatures, but the new atom-sized quantum dots perform at room temperature.

Often referred to as artificial atoms, quantum dots have previously ranged in size from 2-10 nanometers in diameter. While typically composed of several thousand atoms, all the atoms pool their electrons to "sing with one voice", that is, the electrons are shared and coordinated as if there is only one atomic nucleus at the centre. That property enables numerous revolutionary schemes for electronic devices.

Research project leader Robert A. Wolkow described the potential impact saying, "Because they operate at room temperature and exist on the familiar silicon crystals used today's computers, we expect these single atom quantum dots will transform theoretical plans into real devices."

The single atom quantum dots have also demonstrated another advantage - significant control over individual electrons by using very little energy. Wolkow sees this low energy control as the key to quantum dot application in entirely new forms of silicon-based electronic devices, such as ultra low power computers. "The capacity to compose these quantum dots on silicon, the most established electronic material, and to achieve control over electron placement among dots at room temperature puts new kinds of extremely low energy computation devices within reach."

http://www.ualberta.ca/

People with a genetic condition called Williams syndrome are famously gregarious. Scientists, looking carefully at brain function in individuals with Williams syndrome, think they may know why this is so.

The researchers at the Stanford University School of Medicine showed that parts of a particular brain region known as the amygdala react more powerfully in Williams syndrome patients than in developmentally normal subjects - or in subjects with delays in development not caused by Williams syndrome - when exposed to facial expressions conveying positive emotions.

The study will be published Jan. 28 in the Journal of Neuroscience . Biopsychologist Brian Haas, PhD, a postdoctoral researcher at Stanford, shares first authorship of the study with Debra Mills, PhD, of Bangor University in Gwynned, Wales. Haas conducts research in the laboratory of Allan Reiss, MD, the Howard C. Robbins Professor of Psychiatry and Behavioral Sciences at Stanford, who is the paper's senior author. The work is part of an ongoing multicenter collaboration.

Williams syndrome, a rare genetic disorder affecting perhaps one in 10,000 individuals in whom a specific and well-defined chunk of DNA in one chromosome is missing, manifests in a distinctive pattern of physical and behavioral abnormalities including greatly reduced spatial and mathematical reasoning, but relatively less loss of certain verbal abilities or capacity to read others' emotions.

"If you give people with Williams syndrome a picture of a bicycle to copy, they are able to draw the individual components of the bike - the wheels, the handlebars and so forth - but these components will be all over the page. It wouldn't look like a bike," said Haas. "But if you give them pictures of faces and ask them to describe the expressions, or ask them to talk about a story they've heard, they not only show just as much skill as you or I, but in some cases use even more socially and emotionally descriptive language. It's been speculated that they may even be better than the rest of us at picking up social information from facial expressions. We aimed to study the neurological underpinnings of social functioning in these people."

Sociability is one trait emphatically not lacking in people with Williams syndrome. On the contrary, they are invariably sociable - so much so that they will not uncommonly approach and strike up conversations with total strangers. Indeed, these individuals' famous gregariousness can be so pronounced as to occasionally place them in harm's way.

The investigators reasoned that the link between stereotypical sociability associated with Williams syndrome and the characteristic genetic deletion causing the condition might be mediated by a region deep within the brain called the amygdala. This almond-shaped, peanut-sized structure is known to be key to social and emotional processing - reading facial expressions or voices, for example. Lesions of the amygdala can cause a person to lose the ability to make quick "friend or foe" assessments, which have undoubtedly had life-or-death implications in human evolution.

Using two different techniques for objectively measuring brain response, the team showed that when 14 individuals with Williams syndrome looked at photos of faces judged by an independent team of normal reviewers to be especially reflective of a positive emotional state - like happiness - their amygdalas responded much more forcefully than did those of 13 age-matched normally developing subjects. One of those techniques, functional magnetic resonance imaging, was able to localize the increased activity to specific nerve clusters in the amygdala, while another technique, involving monitoring the brain's electrical signals with a device placed on subjects' heads, charted the course of this activity over time.

Earlier work by others had already shown that Williams syndrome patients' amygdalas respond less vigorously to negatively charged stimuli (such as a face exhibiting fear) than do those of developmentally normal subjects. The new study both confirmed that finding and showed, for the first time, that exposure to a positive facial expression triggers a jump in signaling within the amygdala in these individuals, but not in healthy control subjects.

To rule out the possibility that the different response merely reflected IQ differences between normal and Williams syndrome subjects, the researchers also compared the latter with 15 other developmentally challenged subjects whose IQs matched those of the Williams syndrome group. They saw the same result here, as well.

Their reduced amygdala response to negatively charged facial expressions may provide a physiological basis for Williams syndrome patients' relative lack of reticence about approaching and engaging strangers, said Haas. Likewise, he said, the heightened response to positively charged facial expressions suggests that exposure to these smiling faces may be profoundly rewarding to these patients and, therefore, enhance their sociability. It may also mean that social rather than, say, monetary rewards may prove to be better incentives for training persons with the syndrome to compensate for their deficits, Haas speculated.

This differential processing in the amygdala appears to have its roots in Williams syndrome's defining DNA deletion, implying a genetic basis for the difference - and, perhaps, for individual differences among normal people.

In some ways, both the deficits and strengths of the syndrome are the polar opposites of those that typify the far more common syndrome called autism, in which mathematical and visuospatial skills may be not only unimpaired but sometimes pronouncedly enhanced, while functions such as eye contact or gregarious behavior are markedly diminished. But in contrast to Williams syndrome, which is always attributable to the same distinct genetic lesion, "autism is an umbrella covering many different conditions with similar symptoms but a wide range of causes," said Reiss, complicating brain-function analysis of the sort his lab is doing. However, he said, another genetic disorder, called Fragile X syndrome, stems from a genetic abnormality as distinctive and well-characterized as Williams syndrome but often produces the symptoms of autism.

Reiss has applied for funding to study and compare brain function in very young children with these two conditions, in the hope of determining how the loss of specific genes results in specific behavioral changes, how and where these changes are mediated in the brain and what role the environment plays in modifying outcome.

This research holds implications for neurologically normal individuals, too. Studies have shown that more-extroverted people's amygdalas are more responsive to happy faces than less-extroverted people's are, suggesting the involvement of physiological hardwiring in shaping personality traits. "The more we understand about what makes us more or less social beings," said Reiss, "the better we may be able to tolerate one another's differences."

http://med-www.stanford.edu/MedCenter/MedSchool

You come into a doctor's office with severe knee pain. The physician orders an MRI, which reveals substantial loss of cartilage - osteoarthritis, that is - in your knee joint. At this point, not much can be done beyond gulping down palliatives and trying to keep your weight off the joint. But the damage may have started building as much as 20 years earlier, possibly due to a traumatic injury to the affected joint.

Just ask Garry Gold, MD, an associate professor of radiology at the Stanford University School of Medicine. Now 45, Gold sustained a knee injury 20 years ago while playing in a pickup basketball game. These days, he's starting to wish his house, currently being remodeled, didn't have any stairs.

Gold, who has been diagnosed with osteoarthritis, is working with an imaging technology called sodium MRI to diagnose osteoarthritis as long as decades before the onset of physical symptoms. That may spawn new therapies that could possibly have blocked his disease before it put an end to his basketball days.

Gold is collecting young athletes who've suffered damage to the anterior cruciate ligament, or ACL, in their knee - an injury afflicting several hundred thousand people annually in the United States alone. This knee insult is especially common among female athletes. "A good fraction of the Stanford women's basketball and soccer teams either have torn their ACL sometime in the past or will tear it while they're still at Stanford," Gold said. Even when the initial ligament lesion is repaired surgically, victims remain at almost doubled risk for symptomatic osteoarthritis in the injured knee a decade or two down the road, compared with uninjured people.

Using the new imaging technology, Gold and colleagues have been able to spot, soon after such an injury, telltale signs of cartilage deterioration consistent with the development of osteoarthritis.

MRI now in routine use works by pulsing the area to be observed with electromagnetic energy, at a frequency that preferentially excites the protons in water molecules. As the protons settle back to a relaxed state, they send out an electromagnetic burst of their own, which can be picked up by sensors in the apparatus. Because cartilage has lots of water compared with nearby bone, it shows up on a computer-generated image of the region.

But while standard MRI gives a reasonable display of overall cartilage structure, it doesn't tell a diagnostician much about the quality of that cartilage.

"If you look into a big house and you see that it's standing up," Gold said, "you may assume it's going to be safe in the event of an earthquake. But without closer inspection, you don't know much about the integrity of the structure."

If standard MRI is akin to a view of standing timber in the house, the version Gold is using, called sodium MRI, enables the visualization of dry rot infecting and weakening the wood.

A key structural material in cartilage, called glycosaminoglycan, occurs in a complex with sodium, an elemental metal that has its own set of excitation and relaxation frequencies and is more restricted to cartilage than water is.

Sodium MRI has been around for years, but until recently it couldn't be used in clinical settings. For one thing, the magnets employed to excite sodium atoms were too puny, making crisp resolution possible only with tiny creatures such as mice. Gold and his colleague Brian Hargreaves, PhD, assistant professor of radiology at Stanford, have designed improved magnets and software to scale up the technology for human application.

They're on the right track, said Ari Borthakur, a University of Pennsylvania scientist who is not involved in Gold's research but has done pioneering work with sodium MRI since writing his PhD thesis on it some years ago. "Everything his lab has developed is going to be applicable in the clinics," said Borthakur. "As America ages, we're expecting to see a huge increase in osteoarthritis, and any technique that could be used for its early diagnosis, or that could help developing therapies for curing it, or even slowing the progression of cartilage loss, would be tremendous."

Gold and Hargreaves' project is being conducted with funding from the National Institutes of Health and GlaxoSmithKline, an international pharmaceutical company. Neither researcher owns stock in, or receives consulting fees from, the company.

Working with Hargreaves, Gold has imaged the knees of about a dozen volunteers who have suffered a recent ACL injury. In every case so far, significant losses of glycosaminoglycan can be glimpsed under sodium MRI scanning, despite the absence of any sign of damage to cartilage observed with standard MRI. Almost invariably, sodium MRI scans of the injured knee - but not of the other, uninjured one - reveal glycosaminoglycan deficits within three years of the injury, potentially enabling a vastly accelerated diagnosis.

This ought to speed the development of new therapies, and radically lower the cost of doing so, Gold said. The idea is to be able to use glycosaminoglycan loss as a "surrogate marker" of impending osteoarthritis, much as high LDL levels are used to flag people at risk of heart disease - perhaps years before actual symptoms of heart disease manifest. While not everybody with elevated LDL develops cardiovascular disease, this marker has been sufficiently predictive of that condition that regulatory authorities routinely approve drugs based on their ability to lower LDL.

Catching osteoarthritis during its stealth phase may spur clinical trials that would be prohibitively time-consuming and costly if standard MRI were employed, because of the huge lag from the time of an ACL injury until the time cartilage deterioration can be detected by that old method.

With sodium MRI, cohorts of treated vs. untreated at-risk patients could be imaged over time to see if, within a few years of the injury, a drug or a lifestyle change is reducing or arresting the loss of glycosaminoglycan from the ligament. Once promising drugs or lifestyle changes are identified, they could then be administered to at-risk patients long before symptoms surface, Gold said.

As for Gold himself, he has yet to see what his own damaged knee looks like under sodium MRI. The 6-foot-6 once-avid amateur basketball center's knee is too big for even his improved new experimental apparatus to fit. It's probably too late for any kind of imaging to do Gold much good now, anyway. He already knows he's got arthritis. "I don't even want to look," he said.

http://med.stanford.edu/

Melanotan (an unlicensed medicine dubbed the "tan jab") can cause rapid changes in the appearance of moles, warn skin experts in this week's BMJ.

There are two types of Melanotan - Melanotan I and Melanotan II. They work by increasing the levels of melanin (the body's natural pigment that protects us from the sun) resulting in a suntan.

Melanotan has not been tested by the medicines regulator, but both products are being advertised and sold illegally as an injectable tan on the internet and in some tanning salons and body building gyms.

The authors describe two patients attending their dermatology clinic with rapidly changing moles and an intense tan, despite their fair skin type. They were both sunbed users and both had injected Melanotan I and II, bought from the internet, shortly before their moles changed.

The Medicines and Healthcare products Regulatory Agency (MRHA) recently raised concerns about the health risks of these counterfeit drugs, say the authors. These cases highlight a further area of concern - changes in the appearance of existing moles.

They warn that unregulated use of Melanotan may lead to an increase in the number of patients seeking medical advice about changing moles and may even confuse the diagnosis. They suggest healthcare professionals look out for unexpected tanning as a clue to such use.

http://www.bma.org.uk

Many studies have shown that breastfeeding appears to reduce the chance of children developing asthma.

But a newly published study led by a University of Alberta professor has found that eating fast food more than once or twice a week negated the beneficial effects that breastfeeding has in protecting children from the respiratory disease.

The article appears online in the international journal Clinical and Experimental Allergy based in London, England. A number of different findings led the researchers to their conclusion - showing links between fast food and asthma, breastfeeding and asthma, and all three together.

"Like other studies, we found that fast-food consumption was associated with asthma," said the senior author, Dr. Anita Kozyrskyj (pronounced koh-ZUHR-skee), an associate professor in the Department of Pediatrics in the U of A's Faculty of Medicine & Dentistry.

The research confirmed the findings of many other studies about the benefits of breastfeeding in relation to asthma. Kozyrskyj et al. found that breastfeeding for too short a time was linked to a higher risk of asthma, or conversely that children exclusively breastfed 12 weeks or longer as infants had a lower risk.

"But this beneficial effect was only seen in children who did not consume fast food, or only occasionally had fast food," she added.

More than half the children studied ate fast food more than twice a week.

The researchers suggested the prevalence of fast food in today's society may explain why asthma rates keep rising even though more mothers are breastfeeding.

The group did not look at why fast food might cause asthma. But the authors suggest the high fat content, and high salt levels (which can increase twitchy airways and wheezing) may be to blame.

Kozyrskyj, an authority in the area of child health and asthma research, was recruited to the University of Alberta from the University of Manitoba to assume the position of Research Chair, Maternal-Child Health and the Environment.

She conducted the study with Dr. Allan Becker while at the University of Manitoba. The team looked at about 700 Manitoba children, about 250 of whom had asthma and 475 who did not. The research was funded by the Canadian Institutes of Health Research and the analyses were conducted by Xiao-Mei Mai, a postdoctoral student at the U of M.

Kozyrskyj noted that nutrition is only one of many factors involved in asthma. "But this is an interesting finding, and we hope it will stimulate other researchers to follow up and investigate this in more depth, perhaps with a cohort study."

She was a co-author in a different study that received widespread publicity last year when the researchers reported children who received antibiotics in the first year of life were at higher risk of developing asthma later on.

Other research by Kozyrskyj, published in the journal Allergy last year, suggested that girls who do not drink enough milk and are overweight may be at greater risk for asthma.

http://www.med.ualberta.ca/