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Brain Size May Determine Whether You Are Good at Keeping Friends

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Researchers are suggesting that there is a link between the number of friends you have and the size of the region of the brain -- known as the orbital prefrontal cortex -- that is found just above the eyes. A new study shows that this brain region is bigger in people who have a larger number of friendships.

Their study is published on 1 February 2012 in the journal, Proceedings of the Royal Society B.

The research was carried out as part of the British Academy Centenary 'Lucy to Language' project, led by Professor Robin Dunbar of the University of Oxford in a collaboration with Dr Joanne Powell and Dr Marta Garcia-Finana at Liverpool University, Dr Penny Lewis at Manchester University and Professor Neil Roberts at Edinburgh University.

The study suggests that we need to employ a set of cognitive skills to maintain a number of friends (and the keyword is 'friends' as opposed to just the total number of people we know). These skills are described by social scientists as 'mentalising' or 'mind-reading'- a capacity to understand what another person is thinking, which is crucial to our ability to handle our complex social world, including the ability to hold conversations with one another. This study, for the first time, suggests that our competency in these skills is determined by the size of key regions of our brains (in particular, the frontal lobe).

Professor Dunbar, from the Institute of Cognitive and Evolutionary Anthropology, explained: '"Mentalising" is where one individual is able to follow a natural hierarchy involving other individuals' mind states. For example, in the play 'Othello', Shakespeare manages to keep track of five separate mental states: he intended that his audience believes that Iago wants Othello to suppose that Desdemona loves Cassio [the italics signify the different mind states]. Being able to maintain five separate individuals' mental states is the natural upper limit for most adults.'

The researchers took anatomical MR images of the brains of 40 volunteers at the Magnetic Resonance and Image Analysis Research Centre at the University of Liverpool to measure the size of the prefrontal cortex, the part of the brain used in high-level thinking. Participants were asked to make a list of everyone they had had social, as opposed to professional, contact with over the previous seven days. They also took a test to determine their competency in mentalising.

Professor Robin Dunbar, said: 'We found that individuals who had more friends did better on mentalising tasks and had more neural volume in the orbital frontal cortex, the part of the forebrain immediately above the eyes. Understanding this link between an individual's brain size and the number of friends they have helps us understand the mechanisms that have led to humans developing bigger brains than other primate species. The frontal lobes of the brain, in particular, have enlarged dramatically in humans over the last half million years.'

Dr Joanne Powell, from the Department of Psychology, University of Liverpool, said: 'Perhaps the most important finding of our study is that we have been able to show that the relationship between brain size and social network size is mediated by mentalising skills. What this tells us is that the size of your brain determines your social skills, and it is these that allow you have many friends.'

Professor Dunbar said: 'All the volunteers in this sample were postgraduate students of broadly similar ages with potentially similar opportunities for social activities. Of course, the amount of spare time for socialising, geography, personality and gender all influence friendship size, but we also know that at least some of these factors, notably gender, also correlate with mentalising skills. Our study finds there is a link between the ability to read how other people think and social network size.'

Professor Dunbar's research was funded by the British Academy Centenary Research Project and by the British Academy Research Professorship. His research has already examined the different brain sizes of different species, but this study looks at the differences within species. Professor Dunbar published a paper last year, which found that people living near to the Poles needed larger brains for visual processing because of the dimmer light conditions.

Super-human brain technology sparks ethics debate

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A British ethics group has launched a debate on the ethical dilemmas posed by new technologies that tap into the brain and could bring super-human strength, highly enhanced concentration or thought-controlled weaponry.

With the prospect of future conflicts between armies controlling weapons with their minds, the Nuffield Council on Bioethics launched a consultation on Thursday to consider the risks of blurring the lines between humans and machines.

"Intervening in the brain has always raised both hopes and fears in equal measure. Hopes of curing terrible diseases, and fears about the consequences of trying to enhance human capability beyond what is normally possible," said Thomas Baldwin, a professor of philosophy at Britain's York University who is leading the study.

"These challenge us to think carefully about fundamental questions to do with the brain: What makes us human? What makes us an individual? And how and why do we think and behave in the way we do?."

The Council, an independent body which looks at ethical issues raised by new developments in biology and medicine, wants to focus on three main areas of neurotechnologies that change the brain: brain-computer interfaces (BCIs), neurostimulation techniques such as deep brain stimulation (DBS) or transcranial magnetic stimulation (TMS), and neural stem cell therapy.

These technologies are already at various stages of development for use in the treatment of medical conditions including Parkinson's disease, depression and stroke, and experts think they could bring significant benefits, especially for patients with severe brain disease or damage.

GROWING FAST

But they also have huge potential outside the health context. In military applications, BCIs are being used to develop weapons or vehicles controlled remotely by brain signals, and there is big commercial scope in the gaming industry with the development of computer games controlled by people's thoughts.

Speaking at a briefing to launch the consultation, Baldwin said the estimated total global market for all neurotechnologies - including pharmaceuticals for the treatment of brain disorders - is around dollarsignr150 billion.

"Setting pharmaceuticals aside, the value of the market for the devices and technologies we are dealing with is something in the region of dollarsignr8 billion, and growing fast," he said.

Kevin Warwick, a professor of Cybernetics at the University of Reading and a supporter of more neurotechnology research, said some experimental brain technologies had great potential in medicine.

"From the brain signals, a brain computer interface could translate a person's desire to move ... and then use those signals to operate a wheelchair or other piece of technology," he said. "For someone who has locked-in syndrome, for example, and cannot communicate, a BCI could be life-changing."

But he and Baldwin also stressed there are concerns about safety of some experimental techniques that involve implants in the brain, and about the ethics of using such technology in other medicine and other fields.

"If brain-computer interfaces are used to control military aircraft or weapons from far away, who takes ultimate responsibility for the actions? Could this be blurring the line between man and machine?" Baldwin said.

The ethics council's consultation is at www.nuffieldbioethics.org/neurotechnology. The deadline for responses is April 23 and it expects to publish a report with recommendations in 2013.

High Blood Sugar Lowers Chances of Surviving a Heart Attack

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Patients with high blood sugar run an increased risk of dying if they have a heart attack, and diabetics are less likely to survive in-hospital cardiac arrest than non-diabetics, reveals research at the Sahlgrenska Academy, at the University of Gothenburg, Sweden.

Diabetes is common among patients with coronary artery disease, and this is a potentially lethal combination: a thesis from the University of Gothenburg's Sahlgrenska Academy reveals that diabetes in coronary artery disease patients brings a significantly increased risk of premature death.

Smaller chance of surviving

Doctoral student and researcher Petur Petursson investigated the connection between blood sugar disorders and survival following heart attacks and cardiac arrest. His thesis shows that patients with diabetes have a smaller chance of surviving in-hospital cardiac arrest. Diabetes and pre-diabetes are also associated with a less favourable prognosis following coronary artery surgery.

"Type 2 diabetics with suspected coronary artery disease who are on insulin therapy have lower survival," he explains. "We've not been able to demonstrate the exact cause, but much of it may be because those on insulin therapy have more severe disease."

Need for careful management

Petur Petursson says that the results underline the need for careful management of patients with coronary artery disease and the importance of accurately diagnosing and managing blood sugar disorders.

"Medical personnel can pretty much assume that coronary artery disease patients will have some kind of blood sugar disorder, so there must be established strategies for managing these disorders at every heart clinic in the country."

The thesis Aspects of Abnormal Glucose Regulation in Various Manifestations of Coronary Artery Disease was defended on 23 February.

Paul Allen gives $300 million to expand brain research

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Microsoft Corp co-founder Paul Allen has donated an additional dollarsignr300 million to a foundation aimed at expanding research into how the brain works and how best to treat brain-related disorders.

The Allen Institute for Brain Science, based in Seattle, was established with a 2003 contribution of dollarsignr100 million from the former Microsoft executive, who then donated another dollarsignr100 million.

The latest contribution of dollarsignr300 million will support the first four years of a 10-year plan to address critical questions about how the brain works.

Allen Jones, the institute's chief executive officer, said the questions had to be answered if "we are to understand and treat autism, Alzheimer's disease, depression, traumatic brain injury and the myriad other brain-related diseases and disorders that affect all of us either directly or indirectly."

Obesity Raises Death Risk Tied to Sleeping Pills

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Obesity appears to significantly increase the risk of death tied to sleeping pills, nearly doubling the rate of mortality even among those prescribed 18 or fewer pills in a year, researchers have reported.

"Obesity emerged as a marker of increased vulnerability," said Robert Langer, M.D., M.P.H., at the annual American Heart Association's Epidemiology and Prevention | Nutrition, Physical Activity and Metabolism 2012 Scientific Sessions in San Diego.

"The associations between sleeping pills and increased mortality were present, and relatively stronger, even in people aged 18 to 54," said Dr. Langer, a family physician and epidemiologist with the Jackson Hole Center for Preventive Medicine in Jackson, Wyo.

"Obese patients appear particularly vulnerable, perhaps through interaction with sleep apnea," said study co-author Daniel Kripke, a psychiatrist with Scripps Clinic's Viterbi Family Sleep Center in San Diego.

He noted that sleeping pills were previously associated with more and longer pauses in breathing in people with sleep apnea.

Among obese patients, use of sleeping pills was associated with about one extra death per year for every 100 people who were prescribed the medications, Dr. Langer said.

Higher risk for men

Additionally, men who took sleeping pills were about twice as likely to die as women who received the medications, after accounting for other factors, he said.

These new findings were the latest to emerge from a Scripps Clinic-led study of almost 40,000 patients, which was initially published in late February in the open-access online journal BMJ Open.

The research was the first to show that eight of the most commonly used hypnotic drugs were associated with increased hazards of mortality and cancer, including the popularly prescribed medications zolpidem (known by the brand name Ambien) and temazepam (also known as Restoril), Dr. Kripke said.

Those drugs had been thought to be safer than older hypnotics because of their shorter duration of action but were found to have associations with excess deaths no different from the older drugs they have largely replaced.

In order to eliminate the possibility that other factors led to the results, study participants who were prescribed sleeping pills were matched with control patients of similar ages, gender and health who did not receive hypnotics.

The newest findings were delivered by Dr. Langer during an oral session at the American Heart Association conference that focused on drug safety.

For obese patients in the study who had an average body mass index of 38.8, the risk of death was 8.1 times higher on average among those who were prescribed the smallest number of pills (18 or fewer annually) when compared with similar study participants who did not take the medications. The mortality rate was 9.3 times higher on average among obese patients receiving the largest number of pills (132 or more annually).

Death was 4.6 times more likely on average among all patients who received any amount of sleeping pills.

The study cast a shadow over a growing segment of the pharmaceutical industry that expanded by 23 percent in the United States from 2006 to 2010 and generated about dollarsignr2 billion in annual sales.

Using data stored in an electronic medical record that has been in place for more than a decade, the researchers obtained information on almost 40,000 patients cared for by a large integrated health system in the northeastern United States.

The research included 10,531 sleeping pill users who were prescribed the medications for an average of 2.5 years and 23,674 control participants who were not prescribed the drugs. Information came from outpatient clinic visits conducted between Jan. 1, 2002, and Sept. 30, 2006.

"It is important to note that our results are based on observational data, so even though we did everything we could to ensure their validity, it's still possible that other factors explain the associations," said co-author Lawrence Kline, D.O., who is medical director of the Viterbi Family Sleep Center. "We hope our work will spur additional research in this area using information from other populations."

Funding for the study came from the Scripps Health Foundation and other philanthropic sources.

Alternatives to medications

The research should prompt physicians to consider alternatives to hypnotic medications, Dr. Kline said.

Clinicians at the Viterbi Family Sleep Center focus on cognitive therapy that teaches patients to better understand the nature of sleep. For example, some people suffering from insomnia might require less than the eight hours of sleep commonly recommended for each night.

Patients also can benefit from practicing good sleeping habits and relaxation, as well as taking advantage of the body's natural clock, which is driven by the rising and setting of the sun, Dr. Kline said. "Understanding how to use the circadian rhythm is a very powerful tool that doesn't require a prescription," he said.

When insomnia results from emotional problems such as depression, doctors should treat the psychological disorder rather than prescribe sleeping pills that could prove to be harmful, Dr. Kripke said.

Leukemia gene mutations linked to survival odds

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Advances in genetic profiling are paving the way for more precise, and effective, treatment of the aggressive bone marrow cancer known as acute mylogenous leukemia, or AML, according to new research.

Two studies, published in the latest edition of the New England Journal of Medicine, show that genetic testing can guide doctors in how best to use current therapies as well as identify new drug targets.

"As lots of studies identify new alterations in genes in leukemia and other cancers, we need to begin to understand how these alterations in DNA can predict outcomes and determine differences in treatment," said Dr. Ross Levine of Memorial Sloan-Kettering Cancer Center in New York, the lead author of one of the studies.

Such personalized therapy is considered the new frontier for medical practice, and hopes for its success underpin a dollarsignr5.7 billion hostile bid by drugmaker Roche Holding for gene sequencing company Illumina.

The second study, from Washington University in St. Louis, found that 85 percent of bone marrow cells in patients with myelodysplastic syndrome, a blood-related disorder that can precede AML, were linked to mutations in progressive cancer.

The Sloan-Kettering study analyzed bone marrow samples from 502 AML patients for mutations in 18 genes associated with the disease. The researchers were able to categorize two-thirds of the patients into groups clearly defined by their survival chances.

The study found that high-dose chemotherapy improved the rate of survival for patients with three specific genetic mutations, compared with standard-dose chemo.

It also showed that genetic profiling makes it possible to more precisely determine which patients are most likely to have their leukemia return after treatment.

AML is typically cured in about 40 percent of adults between the ages of 18 and 60, according to Levine.

"We were able to identify a very large subset of patients who need new therapies," he said. "Another set was found to do incredibly well with existing therapies, and that is very informative."

The American Cancer Society estimates that AML will be diagnosed in nearly 14,000 Americans this year and that more than 10,000 people will die from the disease.

Gene profiling for AML, and most other cancers, is not currently part of standard clinical practice.

"There are aspects of this that are ready to be adopted," Levine said, adding that the immediate hurdles are the cost of genetic testing and intellectual property rights pertaining to genes that have been patented.

And questions remain about the number of genetic mutations that AML patients should be screened for.

"It is exciting to think that the goal of personalized medicine is quickly approaching," Dr. Lucy Godley said in a NEJM editorial. "But it will require careful thought to implement genomic-based clinical evaluation in a way that is meaningful for patients."

Magnitude 7.2 quake hits central Chile

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A magnitude 7.2 earthquake hit central Chile on Sunday, shaking buildings in the capital of Santiago and the government emergency agency, ONEMI, said it was preventively evacuating some areas of the coast.

The quake struck 64 miles west north west of the town of Talca at a depth of 6.2 miles, the U.S. Geological Survey said.

Magnitude 7.0 quakes or greater are capable of causing widespread, heavy damage.

ONEMI said, however, that the quake was not expected to generate a tsunami off the coast.

The latest earthquake hit near the same central region that struck by a massive 8.8 magnitude earthquake in 2010 and ensued tsunamis in 2010 that killed about 500 people.

The central area is home to some important copper mines, but the bulk of output in the world's top copper exporting nation is concentrated in the far northern region.

Forming Social Memories

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Does a specific memory exist for events involving humans? French researchers from the Vulnerability, Adaptation and Psychopathology Laboratory (CNRS/Université Paris VI) and Canadian researchers from Douglas Hospital, McGill University (Montreal) have identified the internal part of the prefrontal cortex as the key structure for the memory formation of social information.

Social events like a party with friends, a work meeting or a row with a spouse are an integral part of daily life. Our ability to remember these events, and more particularly to remember the people and the relationship we have with them, is absolutely vital if we are to be well adapted to our social life. Different parts of the brain, particularly the hippocampus, are directly involved in learning and memory. Some of these regions are specialized in learning certain types of information, such as the amygdala, which is specialized in the memory of emotions.

The French team (led by Philippe Fossati ) and Canadian team have just identified a specific region of the frontal cortex which, they claim, is specialized in recording and learning social information. They used functional magnetic resonance imaging to measure the brain activity of 17 volunteers as they performed memory tasks involving pictures of social scenes (people and interactions) and nonsocial scenes (landscapes with no humans). This enabled them to identify the internal part of the prefrontal cortex, called the medial prefrontal cortex, as the key structure for encoding the social information in an image.

Previous studies carried out by the same researchers had associated this prefrontal region to processes of thinking about oneself and others. Their work suggests that, over and above emotions, the analysis of specifically human information could facilitate learning and remembering, by using brain structures specialized in the analysis of mental states and empathy. This opens up important perspectives for understanding the mechanisms of human expressions and mental disorders (e.g. schizophrenic disorders and autism), which affect social and relational skills.

Reference: Modulation of memory formation by stimulus content: specific role of the medial prefrontal cortex in the successful encoding of social pictures, Harvey, P.O., Fossati, P., Lepage, M. Journal of Cognitive Neuroscience, February 2007.

Study finds electrotherapy dampens brain connections

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Scientists have discovered how electroconvulsive or electric shock therapy - a controversial but effective treatment - acts on the brains of severely depressed people and say the finding could help improve diagnosis and treatment of mental illness.

Electroconvulsive therapy (ECT) involves first anaesthetizing the patient and then electrically inducing a seizure.

It has a controversial reputation - gained in part because of its role in the 1975 film "One Flew Over The Cuckoo's Nest" starring Jack Nicholson - but is a potent and effective treatment for patients with mood disorders like severe depression.

Yet despite it being used successfully in clinical practice around the world for more than 70 years, scientists have until now not been entirely clear how or why it works.

Now a team from Aberdeen University in Scotland has shown for the first time that ECT affects the way different parts of the brain involved in depression communicate with each other.

In a study published in the Proceedings of the National Academy of Sciences (PNAS) journal they found ECT appears to turn down overactive connections between parts of the brain that control mood and parts that control thinking and concentrating.

This stops the overwhelming impact that depression has on patients' ability to enjoy life and carry out day-to-day activities, they said.

"We've solved a 70-year-old therapeutic riddle," said Ian Reid, a professor of psychiatry at the University of Aberdeen who led the study.

"Our key finding is that if you compare the connections in the brain before and after ECT, ECT reduces the connection strength," he said in a statement.

"For the first time we can point to something that ECT does in the brain that makes sense in the context of what we think is wrong in people who are depressed."

In recent years, experts have developed a new theory on how depression affects the brain that suggests there is a "hyperconnection" between the areas of the brain involved in emotional processing and mood change and the parts of the brain involved in thinking and concentrating.

David Nutt, a professor of neuropsychopharmacology at Imperial College London who was not involved in the ECT study, said its findings "make a lot of sense.

"The disabling of connections between different areas of the brain is what I would have predicted from the depression literature," he said in an emailed comment.

He said the results also chime with a study Nutt published in January which found that psilocybin, the active ingredient in the psychedelic drug known as magic mushrooms, also disrupts this network of connections and may also be effective in treating severe depression.

The electrotherapy study involved using functional magnetic resonance imaging (fMRI) to scan the brains of nine severely depressed patients before and after ECT and then applying complex mathematical analysis to investigate brain connectivity.

Aberdeen University's chair of neuroimaging Christian Schwarzbauer, who devised the new method for analyzing the connectivity data, said it enabled the team to see to what extent more than 25,000 different brain areas communicated with each other.

He said the new method could also be applied to a wide range of other brain disorders such as schizophrenia, autism, or dementia, and "may lead to a better understanding of the underlying disease mechanisms and the development of new diagnostic tools."

The researchers said they now hope to continue monitoring the patients to see if the depression and hyperconnectivity returns. They also want to compare their ECT findings with the effects of other therapies used to treat depression such as psychotherapy and anti-depressants.

Windows Phone struggles to break catch-22 as app makers hold off

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Apps, apps, apps! That is the main challenge that Microsoftand Nokia, who are trying to claw back market share from Apple Inc's iPhone and Google's Android in the red hot smartphone market, face now.

And so far the going does not look too good for the challengers and their warhorse Windows Phone platform.

Apps, short for applications, are small pieces of software that do useful or fun things on cellphones. The huge number and variety of apps in Apple and Google stores are a key factor that has helped the companies emerge as dominant players in the lucrative smartphone market.

On Monday, Microsoft and Nokia said they would invest a total of 18 million euros (dollarsignr23.9 million) into a new mobile application development program, AppCampus, at Helsinki's Aalto University during the next three years.

The move underscores the seriousness with which the two companies view the problem.

Most popular global apps such as Facebook, Twitter, Foursquare and Evernote are available on the Windows Phone platform, but makers of many niche or local apps have shied away.

The number of apps available in the Windows Phone Marketplace now exceeds 65,000, surpassing those at another rival Research in Motion's BlackBerry store. But that is still far short of around half a million apps available on the Apple App Store and Google Play, according to app researcher Distimo.

Worse still, only 37 percent of developers are keen to make apps for Windows Phone, showed the latest IDC/Appcelerator survey. That number, slightly down from the previous survey, compared with the 89 percent interested in iPhone and 79 percent in Android phones.

"Mobile developers' interest for the Windows platform has been for the least very lukewarm over the last two years, with no sign of improvement," Sanford C. Bernstein analyst Pierre Ferragu said.

Microsoft launched its latest Windows Phone 7.5 operating system, Mango, last year to good reviews. And Nokia, struggling to reclaim smartphone handset marketshare from nimbler rivals such as Apple and Samsung Electronics, launched its Lumia line of phones running on Mango late last year.

Lumia phones look sleek and spiffy, with live, tiled icons that automatically update news, weather, pictures and social feeds. But the fewer number of apps and their quality are hobbling the phones' appeal to customers.

Finn Christian Lindholm, a Helsinki-based partner at digital design agency Fjord, believes the latest Windows Phones are interesting enough to challenge the iPhone.

The key to both companies' strategy to gain in the smartphone market would be how they break out of the vicious cycle -- the low sales of the Windows phones holding back app makers, and consumers shunning the phones for lack of the apps they are accustomed to.

"They need to break the Catch-22 before there is enough volume and natural pull," Lindholm said.

SHRINKING MARKETSHARE

Monday's announcement by Microsoft and Nokia is an attempt to find new solutions to the problem, in addition to paying third-party developers for the apps.

They hope the program, which will provide support, coaching and also funding for app makers, will boost the number of unique and outstanding apps on Windows Phone.

It's an uphill road for a new platform. Microsoft's share of the smartphone market fell to just 2 percent last quarter, from 3 percent a year ago and 13 percent four years earlier, according to Strategy Analytics.

Last month, Windows Phone lost also its highly respected chief of developer relations, Brandon Watson, who left for Amazon.com Inc, which is taking on established players in the mobile devices market with its Kindle e-readers.

Apart from Nokia, which has a lot riding on the platform, Microsoft has little support from other handset makers, such as Samsung, which are clearly focused on their Android offerings.

That is not surprising as the other handset makers are struggling to sell their Windows Phone models. They, unlike Nokia, can only dream of payments from Microsoft for promoting and supporting its software. Last quarter, Microsoft paid dollarsignr250 million to Nokia on this account.

NO TALKING TOM CAT

On Friday, Rovio, the maker of the wildly popular Angry Birds game, created a scare when media reports said the latest version of the game -- Angry Birds Space -- will skip the Windows platform.

Rovio Chief Executive Mikael Hed later told Reuters that the company is working toward getting the game to Windows Phone but did not specify when it will be available.

Showing how difficult a task that Microsoft and Nokia face, many small app developers, such as Outfit7 -- maker of the popular Talking Tom Cat app -- and Joby -- which makes a camera app -- said they have no plans to be on Windows Phone either.

Pioneers in augmented reality -- a technology that combines the digital and real worlds, and is one of the hottest areas of wireless -- are also holding back.

"We have enough work in keeping Android and iPhone apps up to date, as well as in enhancing our augmented reality capabilities on them," said Maarten Lens-Fitzgerald, co-founder of Dutch-based augmented reality firm Layar.

Jeff Janer, co-founder and CEO of Springpad, which makes the namesake app that allows users to store, organize and share content, raised the main concern of the app makers: Will the hard work to move to a new platform pay off?

"When considering a new platform, we look to balance cost of development and support against potential return in terms of market opportunity and the ability to cost-effectively reach the market," said Janer, who currently has no plans to develop an app for Windows Phone.

For many small developers, it is a question of cost and how fast they can recoup the investment.

It would probably take six man-months to build an app for Windows phone and if that was contract work it would be dollarsignr60,000 or more, said Adam Saltsman, co-founder of Semi Secret Software, which makes the Wurdle word game.

The small customer base for Windows Phone is forcing developers to charge more for the apps, turning off customers further. Most apps that are available for 99 cents on Google Play cost dollarsignr2.99 on the Windows Phone Marketplace.

Andreas Bernstrom, CEO of Rebtel, one of the most popular Internet-based calling applications on iPhone and Android, said the company has Windows Phone on its development roadmap for later this year but has not yet started work.

"I don't know what the market will be like in six months, maybe we need to focus on tablets or something else," he said.

Jeffrey Glueck, chief executive of Skyfire Labs Inc, which makes the eponymous mobile Web browser, said the main driver for developing on Windows Phone will be carrier requests. "So far, we're only getting requests around Android and iPhone."

That is one more challenge for Microsoft and Nokia.

Leukemia Stem Cells Identified

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Stem cell researchers at UCLA have identified a type of leukemia stem cell and uncovered the molecular and genetic mechanisms that cause a normal blood stem cells to become cancerous.

The discovery may lead to new therapies that target these leukemia stem cells, attacking the disease at its very root and killing the early cells that give rise to the mature cancer cells. The study appears in the May 22, 2008 issue of the journal Nature.

Scientists now believe stem cells are responsible for the origin of many cancers and their ability to become drug resistant and spread throughout the body. Current cancer therapies don't target cancer stem cells, only the cancer cells that are generated by them. Scientists theorize that the cancer stem cells -- a very small population when compared with mature cancer cells - lay dormant while the cancer cells are killed. Later, sometimes years later, the cancer stem cells begin to self-renew and differentiate into malignant cells, causing a recurrence of the disease.

If scientists could understand the biology of cancer stem cells and find a way to kill them, it might provide what the oncology research community never talks about -- a potential cure for certain cancers. If the cancer stem cells could be sought out and eliminated from the body, the cancer could not re-grow.

Led by Dr. Hong Wu, a professor of medical and molecular pharmacology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, the UCLA team has for the first time identified and isolated the stem cells responsible for a type of leukemia known as T-cell or acute T-lymphoblastic leukemia, an aggressive and deadly cancer that , can occur in both children and adults. The team also discovered the mechanisms by which blood stem cells -- the cells that become the various cells in the blood supply -- are converted to malignant leukemia stem cells, providing potential targets for therapies to home in on and attack those stem cells.

"One of the main challenges in cancer biology is to identify cancer stem cells and define the molecular and genetic events required for transforming normal cells into cancer stem cells," said Wu, who also is a researcher at UCLA's Jonsson Comprehensive Cancer Center and senior author of the Nature study. "With this study, we've been able to do that in one type of leukemia."

In mouse models that developed T-cell leukemia, the team studied the cancerous cells and, using a sorting method that sought out certain cell surface markers, was able to identify the leukemia stem cells. Those cells were isolated and then transplanted into other mouse models to see if they developed T-cell leukemia, a sign that the team had been successful in finding the leukemia stem cells.

The team also wanted to know how blood stem cells become cancerous and studied the cells at the molecular and genetic level to uncover those mechanisms.

"We thought that multiple genetic or molecular alterations would have to occur for cancer to develop," said Wei Guo, a postdoctoral student in Wu's lab and the first author of the study. "In this case, we were able to find those alterations."

The alterations found that collaboratively contribute to leukemia stem cell formation were the deletion of the PTEN tumor suppressor gene, a chromosomal translocation involving c-myc, a gene known to result in cancer that is usually regulated and kept in line, and the activation of a cell signaling pathway called beta catenin.

Wu and her team currently are testing therapies that target the alterations they discovered, hoping to interrupt the process that causes the blood stem cells to become leukemia stem cells, thereby preventing the cancer. They're also looking for other alterations that might be at play in transforming the normal stem cells into cancerous stem cells.

Knocking Out Survival Protein Could Aid Leukemia Treatment

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An effective way to fight leukemia might be to knock out a specific protein that protects cancer cells from dying, a new study shows. The findings suggest that a drug that can block this “survival protein” might on its own be an effective therapy.

Health & Medicine

Leukemia
Lymphoma
Cancer
Lung Cancer
Brain Tumor
Skin Cancer

Reference

Leukemia
Lymphoma
Tumor suppressor gene
BRCA1

But such a drug used in combination with several existing drugs might also offer an effective one-two punch against drug-resistant forms of chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). The two forms of cancer kill about 20,500 Americans yearly.

The survival protein is called Mcl1. It usually helps keep normal cells healthy and is involved in the development of the components of the immune system, but it can also help prolong survival of cancer cells.

Cells with an overabundance of the protein are also more resistant to anticancer drugs such as rituximab, which has revolutionized the treatment of certain chronic and acute leukemias.

“Our findings demonstrate that Mcl1 may be an effective target for drugs directed against CLL and ALL,” says principal investigator John C. Byrd, professor of internal medicine and director of the hematologic malignancies program at Ohio State's James Cancer Hospital and Solove Research Institute.

“These results give us a rationale for lowering the amount of this protein in CLL cells and suggest that this should enhance the action of rituximab and perhaps other agents as well.”

Rituximab is an antibody-based drug that targets CLL and ALL cells and causes the cells to self-destruct. “We've shown that knocking down Mcl1 can, by itself, cause CLL cells to die, and that this effect might enhance the activity of rituximab,” says first author Rehan Hussain, a postdoctoral fellow with Ohio State's Comprehensive Cancer Center.

Byrd, Hussain and their collaborators conducted this research using cancer cells from 17 CLL patients and ALL cell lines grown in the laboratory.

The investigators placed molecules called small interfering RNA (siRNA) inside the cells and found that the tiny molecules greatly reduced the amount of the survival protein, causing many of the cells to die. The effect was the same even in cells that came from patients with advanced cancer or from patients with tumors that resisted conventional treatment.

When the researchers treated cells with both siRNA and the drug rituximab, the combination killed significantly more leukemia cells than the drug alone. Overall, says Byrd, “Our data indicate that specifically targeting Mcl1 might be effective in the treatment of CLL, particularly when combined with rituximab.”

Funding from the National Cancer Institute, the Leukemia & Lymphoma Society and the D. Warren Brown Foundation supported this research. Byrd is the D. Warren Brown Professor of Leukemia Research and a Clinical Scholar of the Leukemia & Lymphoma Society. The study by researchers at the Ohio State University Comprehensive Cancer Center is published online in the journal Clinical Cancer Research.

Potential New Way To Make A Good Anti-Leukemia Drug Even Better

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A recently identified cancer-causing protein makes the anti-leukemia drug imatinib, less effective. By blocking the protein, an international team of researchers was able to slow the spread of leukemia cells in culture.

The study, which will appear online on October 20 in the Journal of Experimental Medicine, suggests that the most effective treatment for leukemia may rely on a combination of targeted drugs, rather than a single miracle drug.

Imatinib is currently the most popular therapy for chronic myeloid leukemia (CML). CML is a type of blood cancer that is most common among middle-aged adults and accounts for 15-20% of all cases of adult leukemia in the western world. Accumulation of cancer cells in the patient's blood causes infections, anemia, and other potentially life-threatening complications.

CML is associated with the abnormal fusion of a portion of chromosome 21 with a cell growth-promoting enzyme called ABL, which makes the enzyme perpetually active. Imatinib slows down the spread of cancer by blocking the enzyme's activity. But the drug doesn't work in everyone and resistance often develops, most likely because the drug only targets mature cells, leaving self-renewing cancer stem cells behind.

Now, Xiaoyan Jiang and a team of researchers from the British Columbia Cancer Agency in Vancouver and other institutions may have discovered what protects the stem cells from imatinib.

The team found that a protein called AHI-1, which has been found in leukemia cells in the past, is highly expressed in CML stem cells. When Zhou and colleagues blocked AHI-1 in cancer cells from imatinib-resistant CML patients, they restored the ability of the drug to kill the cells. The next step, says Jiang is finding a drug that blocks AHI-1, which could potentially be given in combination with imatinib in the future.

Stop Signal for Leukemia Stem Cells

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There are numerous specialized growth factors that are responsible for cells of different tissues of our body to divide and differentiate when needed. These hormone-like factors bind to matching receptors on the surface of their target cells and thus give order for the cell to divide. However, a single genetic alteration can be sufficient for the whole system to get out of control. If, for example, the gene for such a growth factor or for the matching receptor is hyperactive, then the cell permanently receives signals to divide -- and this can result in cancer.

Such defective growth signals play a role in many cancers. Thus, breast cancer cells in about 20 percent of affected women form too many receptors for the Her2/neu growth factor; in bowel cancer doctors frequently find an overproduction of the EGF growth factor.

Jointly with colleagues from France, Canada and the U.S., scientists headed by Professor Dr. Andreas Trumpp of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now discovered that in T-cell acute lymphoblastic leukemia (T-ALL), too, malignant growth is driven by a particular growth factor. In this case, it is the insulin-like growth factor 1 (IGF1) which plays the key role.

The investigators found out that there is an oversupply of IGF1 receptors in T-ALL. The leukemia cells therefore become particularly sensitive to IGF1 signals. When the researchers blocked the IGF1 receptors using specific inhibitors or turned off the gene coding for the receptor, the blood cancer cells ceased to grow. This worked both in murine cancer cells and in human leukemia cells.

However, blockage of the IGF1 signal not only stopped cancer cell growth. Moreover, the dangerous cancer stem cells lost their capability of self-renewal. This was shown by the investigators in a classic experiment called serial transplantation. They transplanted T-ALL cells that formed only small amounts of IGF1 receptors on their surface into mice. Although T-ALL cells normally always cause leukemia in recipient animals, only very few mice developed leukemia after injection of the modified T-ALL. For the team this was the most important clue that leukemia stem cells were either absent or no longer active, because they are the only ones that can initiate leukemia.

"We only need to reduce the level of IGF1 receptors slightly in order to deprive cancer stem cells of their self-renewal capacity. Apparently, leukemia stem cells are particularly dependent on strong IGF1 signals," explained Dr. Hind Medyouf, first author of the article.

Acute lymphoblastic leukemias are the most frequent malignancies in children; however, elderly adults may be affected, too. The group's results open up new prospects for treatment, because substances inhibiting the IGF1 receptor are already available and are currently being tested for other types of cancers such as breast cancer in clinical trials. Andreas Trumpp, a stem cell specialist, explains: „Elderly T-ALL patients have a particularly high recurrence rate after seemingly successful chemotherapy. Inhibition of the IGF1 signaling pathway would target the leukemia stem cells in particular and might therefore prevent recurrence of the cancer."

How To Design A Cancer-Killing Virus

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One new way to treat individuals with cancer that is being developed is the use of viruses that infect and kill cancer cells while leaving normal cells unharmed. These viruses are known as virotherapeutics.

In a new study, David Kirn and colleagues at Jennerex Biotherapeutics, San Francisco, have described the development of a new virotherapuetic with antitumor effects in both mice and rabbits.

After selecting a highly potent strain of poxvirus that was able to traffic to tumors when administered intravenously to mice the authors engineered the virus such that it would target only specific cancer cells -- those with increased expression of a protein known as E2F and/or activation of signaling downstream of a protein known as EGFR.

Further engineering to enable the virus to produce the soluble factor GM-CSF was designed to enhance the induction of anti-tumor immune responses. In addition to its antitumor effects in mice and rabbits, the virotherapeutic showed high selectivity for cancer cells in tumor-bearing rabbits and in human tissue samples, leading the authors to suggest that this virotherapeutic should be tested in clinical trials for the treatment of cancer.

Article: Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963, Journal of Clinical Investigation, October 25, 2007.