Cambridge-based researchers provide new evidence that the human brain lives "on the edge of chaos", at a critical transition point between randomness and order. The study, published March 20 in the open-access journal PLoS Computational Biology, provides experimental data on an idea previously fraught with theoretical speculation.

Self-organized criticality (where systems spontaneously organize themselves to operate at a critical point between order and randomness), can emerge from complex interactions in many different physical systems, including avalanches, forest fires, earthquakes, and heartbeat rhythms. According to this study, conducted by a team from the University of Cambridge, the Medical Research Council Cognition & Brain Sciences Unit, and the GlaxoSmithKline Clinical Unit Cambridge, the dynamics of human brain networks have something important in common with some superficially very different systems in nature. Computational networks showing these characteristics have also been shown to have optimal memory (data storage) and information-processing capacity. In particular, critical systems are able to respond very rapidly and extensively to minor changes in their inputs.

"Due to these characteristics, self-organized criticality is intuitively attractive as a model for brain functions such as perception and action, because it would allow us to switch quickly between mental states in order to respond to changing environmental conditions," says co-author Manfred Kitzbichler.

The researchers used state-of-the-art brain imaging techniques to measure dynamic changes in the synchronization of activity between different regions of the functional network in the human brain. Their results suggest that the brain operates in a self-organized critical state. To support this conclusion, they also investigated the synchronization of activity in computational models, and demonstrated that the dynamic profile they had found in the brain was exactly reflected in the models. Collectively, these results amount to strong evidence in favour of the idea that human brain dynamics exist at a critical point on the edge of chaos.

UK scientists found that a type of angiogenesis inhibitor used to treat cancer can actually encourage rather than stop tumour growth when given at low doses.

The researchers who carried out the study are from the The Institute of Cancer, Queen Mary, University of London, the Institute of Cancer Research (ICR), a college of the University of London, and the Beatson Institute for Cancer Research, Glasgow and they published their findings in the 22 March online issue of Nature Medicine.

Angiogenesis inhibitors are designed to stop tumours growing by cutting off their blood supply. They work by changing the way molecules that control cell behaviour send signals to each other, a very complex process.

In this study, lead investigator Dr Kairbaan Hodivala-Dilke of The Institute of Cancer and colleagues focused on an experimental angiogenesis inhibitor called cilengitide that has not yet been licensed for patients.

This type of angiogenesis inhibitor targets integrins, cell receptors that help to regulate how cells stick to other cells and to the cell-matrix (tissue that is not part of a cell) and also play a role in processing signals that pass between cells and regulate many important processes like growth, wound healing, and immune system function.

In this study, the researchers showed through laboratory studies that cilengitide can change the way integrins and VEGF receptors move inside blood vessels. Vascular Endothelial Growth Factor (VEGF) is a protein that stimulates growth of blood vessels.

They found that this type of angiogenesis inhibitor can actually promote cell growth and blood vessel formation instead of blocking it because it changes the way that integrin and VEGF receptors move inside blood vessels

The researchers also suggested that what they have found could be a previously unknown characteristic of drugs similar to cilengitide.

Sometimes just a small change in the way a drug is used, or a small change to its composition can have a very large effect on how it works, said Dr Lesley Walker, director of cancer information at Cancer Research UK who said this study was important because:

"It may help to explain the mixed results previously seen in patients and turn around disappointing results so people may still benefit from the drug without the potential harm."

"Other anti-angiogenesis drugs like sunitinib (Sutent) and bevacizumab (Avastin) have proven effective enough for use in the NHS but there is still need to understand why they can sometime fail. It may be that there are similar mechanisms at work," she added.

Another paper published this month in the journal Cancer Cell shows that sunitinib (Sutent), can sometimes encourage tumour growth rather than stunt it.

Hodivala-Dilke told the BBC that:

"We've got evidence now that low doses [of cilengitide] can enhance tumour growth. So there is no benefit of giving a high dose, which then drops, and then a high dose again."

However, this does not mean it won't work at all, and it is important that the trials continue, she added, "but there is this caveat".

She explained that it might be more effective to give the drug via an infusion pump which would keep the dosage at the right level.

Co-investigator Dr Andy Reynolds, of the Breakthrough Breast Cancer Research Centre at the ICR, said in a press statement:

"Our study revealed a previously unknown mechanism through which drugs such as cilengitide behave."

"These results may explain why initial results from early stage clinical trials have not been as promising as hoped," said Reynolds.

"Knowledge of this mechanism will help us develop new ways to make these drugs as effective as possible. In the future, we may be able to combine these inhibitors with other drugs to maximise their effectiveness for patients," he added.

"Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors."

Obese women may be putting themselves at greater risk of breast cancer by not undergoing regular screening. According to new research by Dr. Nisa Maruthur and her team from The John Hopkins University School of Medicine in Baltimore, USA, seriously obese women are significantly less likely to say they have undergone a recent mammography than normal weight women, especially if they are white. Maruthur's findings are published online this week in Springer's Journal of General Internal Medicine.

Breast cancer is the second leading cause of cancer death among women in the US. Mammography screening has been proven to reduce the number of deaths from breast cancer; current guidelines recommend that women over the age of 40 undergo a mammography every couple of years. Obesity is also an important risk factor for both the development of, and death from, postmenopausal breast cancer.

Maruthur and colleagues conducted a systematic review and meta-analysis of 17 studies comprising over 276,000 participants, to look at whether overweight and obese women are less likely to have had a recent mammography than normal weight women. They also looked at the differences in mammography take-up between white and black obese women in three of the studies. They found that severely obese women were 20 percent less likely to have had a recent mammography than normal weight women. However, this was not the case among black women.

The authors highlight a number of reasons why obese women may not be undergoing breast cancer screening, including a delay in taking up medical care because of poor self-esteem and body image, embarrassment, a perceived lack of respect from their health care providers and unwanted weight loss advice. According to the authors, obesity may be a marker for sub-optimal health behavior in general, of which mammography is simply one element. The authors also suggest that there are racial differences in obesity-related body image which may explain the difference in take-up of mammography between white and black women.

The authors conclude that "the main implication of our study is that a lack of routine screening mammography may explain some of the increased breast cancer mortality in obese postmenopausal women. Clinicians should be aware of this disparity in evaluating their own practices."

Pulmonary Fibrosis (PF) claims a life every 13 minutes in the U.S., the same number of lives each year as to breast cancer; yet most Americans have never heard of the disease until it strikes them, or someone they love. The Coalition for Pulmonary Fibrosis (CPF) launched a new public service announcement (PSA) to increase awareness of PF, which affects more than 128,000 Americans. Since 2001, prevalence has increased an alarming 156 percent, yet awareness and understanding of PF remains low in the general public and medical community. The goal of the PSA is to draw increased national attention to PF by educating the public on this rapidly progressing and ultimately fatal disease, and to urge people to support the CPF in its efforts to help patients and fund research efforts to find a cure.

The PSA, entitled 'Target', portrays a need for increased public awareness of PF by noting the rapidly increasing prevalence of the disease and the need to accelerate efforts to help patients, and understand and treat PF. The aggressive tone of the PSA highlights the ever-increasing need to work with the CPF to help the community of patients and researchers it serves,

"Our goal was to create a dramatic visual metaphor that clearly demonstrates the random and deadly nature of PF. The customized visual effect of an animated high tech moving target in an urban environment delivers a sobering message that 128,000 are now dying from PF with another 48,000 who will be 'targeted' this year by the deadly disease," said David C. Bojorquez, Director - Filmmaker with David Productions, the company that created the PSA for the CPF.

The video conveys the stealth nature of the fatal lung disease that targets its victims randomly. There is no known cause and there are no treatments, making PF a mystery to scientists, and a shocking and devastating diagnosis to patients and their families. It is the CPF's intention to create an open dialogue about the disease with the strong video message in hopes that it will lead to public support of the CPF's continuing efforts in patient services and research efforts to find a cure.

"We are so excited about this opportunity to share this well-produced video with the public. Our patients have long waited for a national voice in the media, and we are filling that void with this production," said Mishka Michon, chief executive officer for the CPF. "Our goal is for this video to spread virally throughout the Internet and for it to also be widely broadcast on television and cable stations nationwide. It is critically important that attention be paid before hundreds of thousands more lives are claimed by PF in the coming years."

About Pulmonary Fibrosis (PF)

Pulmonary Fibrosis (PF) is a lung disorder characterized by a progressive scarring - known as fibrosis -- and deterioration of the lungs, which slowly robs its victims of their ability to breathe. Approximately 128,000 Americans suffer from PF, and there is currently no known cause or cure. An estimated 48,000 new cases are diagnosed each year. PF is difficult to diagnose and an estimated two-thirds of patients die within five years of diagnosis. Sometimes PF can be linked to a particular cause, such as certain environmental exposures, chemotherapy or radiation therapy, residual infection, or autoimmune diseases such as scleroderma or rheumatoid arthritis. However, in many instances, no known cause can be established. When this is the case, it is called idiopathic pulmonary fibrosis (IPF).

About the CPF

The CPF is a 501(c)(3) nonprofit organization, founded in 2001 to accelerate research efforts leading to a cure for pulmonary fibrosis (PF), while educating, supporting, and advocating for the community of patients, families, and medical professionals fighting this disease. The CPF funds promising research into new approaches to treat and cure PF; provides patients and families with comprehensive education materials, resources, and hope; serves as a voice for national advocacy of PF issues; and works to improve awareness of PF in the medical community as well as the general public. The CPF's nonprofit partners include many of the most respected medical centers and healthcare organizations in the U.S. With more than 19,000 members nationwide, the CPF is the largest nonprofit organization in the U.S. dedicated to advocating for those with PF.

An analysis in CMAJ expresses reservations about recommendations to raise fish consumption for health benefits. Dr. David Jenkins and his team, St. Michael's Hospital, Toronto, say such advice may not consider environmental issues, and that further research to explain the benefits of omega-3 fatty acids is required. http://www.cmaj.ca/press/pg633.pdf.

Around the world, the medical community and health agencies praise fish consumption for health benefits. In developed countries, people have been advised to double or triple their fatty fish intake.

Evidence and unsuccessful studies in demonstrating a significant health benefit from omega-3 fatty acids have received little interest, suggesting that not all individuals do indeed benefit from fish consumption. This study examines the facts to prove the health benefits of fish.

The researchers explain that global fisheries are in serious crisis with the present fish consumption levels because demand outweighs supply. There are severe consequences for the food security of poorer countries and coastal communities, as diminishing stocks are redirected from local to affluent markets. Since the late 1980's, global stocks have been declining and more than a hundred cases of marine extinctions have been reported.

"These trends imply the collapse of all commercially exploited stocks by mid-century," the authors write. "Yet the dire status of fisheries resources is largely unrecognized by the public, who are both encouraged to eat more fish and are misled into believing we live in a sea of plenty."