Exercise offers cancer survivors significant improvements in quality of life

For many cancer survivors, a better quality of life is as close as the nearest pair of sneakers. That's because a growing body of research, including two recent studies led by Yale Cancer Center, show that exercise is a powerful way for survivors to improve quality of life.

31 may 2015--The studies were presented at the 2015 Annual Meeting of the American Society of Clinical Oncology in Chicago. The first evaluated the effect of the LIVESTRONG at the YMCA program on cancer survivors who participated in twice-weekly, 90 minute exercise sessions for 3 months at local YMCAs. The other study explored whether home-based exercise programs that encouraged brisk walking could improve fatigue and quality of life for ovarian cancer survivors. Both studies showed exercise to be a potent tool for survivors to improve life in many areas.

The LIVESTRONG at the YMCA study was conducted by Dr. Melinda Irwin, associate professor of Epidemiology in Yale School of Public Health and associate director of population sciences at Yale Cancer Center; and Dr. Jennifer Ligibel of Dana Farber Cancer Institute. It evaluated 186 participants for quality of life, physical activity and fitness. After 12 weeks, participants were shown to experience significant increases in physical activity (71 percent exercising a minimum of 150 minutes/week vs. 26 percent for the control group); and improvements in both overall quality of life and fitness performance (according to a six- minute walk test). The participants had been diagnosed with stages I-IV of cancer and 50 percent had breast cancer. In addition, at the outset of the program, the majority of the participants had been inactive.

"For many people, quality of life is compromised after a cancer diagnosis. This study showed that exercise can improve patients' lives in a myriad of ways, regardless of how active they were in the past," said Irwin, first author on the study. "In addition to quality of life, physical activity is associated with risk of dying from cancer. The LIVESTRONG at the YMCA program could be a national model to increase exercise in cancer patients across the country."

The WALC study, conducted at Yale and led by Dr. Irwin, is the largest exercise trial of ovarian cancer survivors, It enrolled 144 ovarian cancer survivors who were not physically active and randomized them to an exercise group or control group. Each group received a weekly call from a counselor to discuss a health topic relevant to ovarian cancer survivors. For the exercise group, women also received physical activity counseling from a certified cancer exercise trainer during the calls.

The results showed that a moderate-intensity walking program can improve ovarian cancer survivors' quality of life, in particular physical functioning, improvement in pain and reduced fatigue. Women were interested in exercising and able to do so at recommended levels even though 55% had stage III or IV disease and 25% experienced a recurrence during the trial.

"Our hope is that this study will encourage survivors of even late-stage cancers to consider exercise as a way of coping with a number of issues that come with a cancer diagnosis," said Dr. Yang Zhou, first author on the study. "We also hope oncologists will use this study and others like it to refer patients to survivorship programs that incorporate exercise."

More information: "Randomized trial of exercise on quality of life and fatigue in women diagnosed with ovarian cancer: The Women's Activity and Lifestyle Study in Connecticut (WALC)." J Clin Oncol 33, 2015.abstracts.asco.org/156/AbstView_156_146487.html

Provided by Yale University

Experts on aging: UN Sustainable Development Goals discriminatory, ageist

One of the main health targets proposed by the UN Sustainable Development Goals (SDG) is to reduce by one-third premature mortality from non-communicable diseases such as cancer, stroke and dementia. The goals for 2016-2030 define premature mortality as deaths occurring among people aged 69 years old or younger.

30 may 2015--The proposed SDG target sends an unambiguous statement to UN member states that health provision for younger groups must be prioritised at the expense of people aged 70 or more, according to the international group of signatories of the letter published in The Lancet. The implication for all countries, the UK included, is that resources allocated to conditions such as diabetes and cardiovascular disease should be diverted from older people in order to comply with this global target.

Prof Peter Lloyd-Sherlock, professor of social policy and international development at UEA and lead author of the letter, wrote it in response to research about the SDGs, which was also published in The Lancet in January 2015. Other authors and signatories of his letter include representatives from The Alzheimer's Society, Age UK, and HelpAge International.

Prof Lloyd-Sherlock said: "This premature mortality target is highly unethical, since it unjustifiably discriminates against older people and is explicitly ageist. Also, it lacks any scientific validity."

The letter said the SDG target 'has the potential to undermine cherished, fundamental principles of universality and health as a right for all. Put simply, it tells policy makers, particularly in poorer countries that older people do not matter.

'This target will inevitably reinforce the ageist bias that pervades many aspects of health care decision-making.'

Baroness Sally Greengross, former director of Age Concern England and a signatory of the letter, said: "If adopted, this UN target could lead to institutionalised discrimination against older people in health care, both here in the UK and globally."

The letter calls on the UN to urgently reconsider the framing of this health target in order to avoid setting 'policy priorities that blatantly exclude those people who are often in the greatest need and face the most hardship.'

Prof Lloyd-Sherlock said: "The SDGs are not quite set in stone yet, so we have a final opportunity to impress upon the UN the need to alter this explicitly ageist health target. If this doesn't happen, people aged 70 and over will become second-class citizens as far as health policy is concerned."

More information: Comment: 'A premature mortality target for the SDG for health is ageist' is published in The Lancet on 29 May 2015.

Provided by University of East Anglia

Benefits of calorie restriction on par with balancing protein and carb intake in mice

Solon-Biet et al. find that short-term ad libitum lowprotein, high-carbohydrate diets improve levels of insulin, glucose, lipids, and HOMA. LPHC diets under ad-libitumfed conditions generate the metabolic benefits of caloric restriction without a 40 percent reduction in total caloric intake. Credit: Solon-Biet et al./Cell Reports 2015

Cutting calories through dietary restriction has been shown to lower cholesterol, improve insulin sensitivity, and even prolong life in mammals. Now, new research publishing on May 28th in Cell Reports shows that, at least in mice, low protein, high carbohydrate diets can provide benefits similar to those obtained with calorie restriction.

29 may 2015--"We've shown that when compared head-to-head, mice got the same benefits from a low protein, high carbohydrate diet as a 40% caloric restriction diet," says senior author Stephen Simpson, Academic Director of the University of Sydney's Charles Perkins Centre. "Except for the fanatical few, no one can maintain a 40% caloric reduction in the long term, and doing so can risk loss of bone mass, libido, and fertility."

The investigators compared three 8-week diets varying in protein-to-carbohydrate ratio under conditions where food was restricted or food was available at all times. Of the three, low protein, high carbohydrate (LPHC) diets offered when food was always available delivered similar benefits as calorie restriction in terms of insulin, blood sugar, and cholesterol levels, despite increased food intake.

Even though the mice on LPHC diets ate more when food was always available, their metabolism was higher than that of mice on the calorie-restricted diet, and they did not gain more weight. Calorie restriction did not provide any additional benefits for LPHC mice.

Additional research is needed to determine how LPHC diets affect long-term metabolic health and survival, as well as to what extent the type and quality of proteins and carbohydrates matter. "An important next step will be to determine exactly how specific amino acids, the building blocks of proteins, contribute to overall health span and lifespan," says lead author Samantha Solon-Biet, also of the Charles Perkins Centre.

If the study's results apply to humans, adjusting protein and carbohydrate intake could lead to healthier aging in a more realistic manner than drastically cutting calories. "It still holds true that reducing food intake and body weight improves metabolic health and reduces the risk of diseases like type 2 diabetes, obesity, and fatty liver disease," says Simpson. "However, according to these mouse data and emerging human research, it appears that including modest intakes of high-quality protein and plenty of healthy carbohydrates in the diet will be beneficial for health as we age."

More information: Cell Reports, Solon-Biet et al.: "Dietary protein to carbohydrate ratio and caloric restriction: comparing metabolic outcomes in mice" dx.doi.org/10.1016/j.celrep.2015.05.007

Provided by Cell Press

Frailer older patients at higher risk of readmission or death after discharge from hospital

Frailer older patients are at higher risk of readmission to hospital or death within 30 days after discharge from a general internal medicine ward, but health care professionals can assess who is at risk using the Clinical Frailty Scale, according to a study in CMAJ (Canadian Medical Association Journal).

28 may 2015--Readmission within 30 days after hospital discharge is common and also costly for the health care system. Identifying at-risk patients and addressing the factors contributing to readmission can help reduce recurrences. However, current tools are not able to predict accurately who might be at risk of readmission.

Researchers assessed whether the Clinical Frailty Scale can help predict readmission or death within 30 days after hospital discharge in a group of 495 patients at 2 Alberta hospitals. The Clinical Frailty Scale, an easy-to-use tool developed several years ago, can be used at the bedside by physicians and other health care professionals to determine frailty. The scale measures difficulty in daily living activities with mild frailty (score of 5) corresponding to difficulty with 1 or more complicated daily living activities such as finances, shopping, meal preparation and housework. Moderate frailty (score of 6) indicates difficulty in bathing, dressing or climbing stairs. Severe frailty (score of 7) means a patient is physically or mentally dependent on someone for 3 or more daily living activities.

Of the patients enrolled in the study, half were women, and the median age was 64 years. One-third of the patients (162) were frail, with a score of 5 or higher on the Clinical Frailty Scale in the week before admission to hospital. Within 30 days after discharge, 85 patients (17%) were readmitted or had died. Compared with nonfrail patients, frail patients were at greater risk of readmission or death within 30 days (24% v. 14%), especially those with moderate or severe frailty (31% v. 14%). Inclusion of frailty assessments improved the prediction of post-discharge outcomes, leading the authors to suggest that this assessment be included in discharge planning procedures to help identify patients at highest risk of poor transition from hospital to home.

The researchers suggest that a variety of factors may contribute to readmission to hospital.

"Although frailty or vulnerability before becoming ill may affect outcomes after discharge, patients in hospital may also experience an acquired, transient period of risk for adverse events that is harmful in addition to the stress of the acute illness," writes Dr. Finlay McAlister, University of Alberta, with coauthors. "This 'post-hospital syndrome' is a multidimensional construct that incorporates sleep deprivation, cognitive stress, poor nutrition and physical pain. Patients who are already frail before hospital admission may be more sensitive to the stresses of this syndrome and at higher risk of readmission and poor outcomes."

The Clinical Frailty Scale can be a useful tool for health care professionals to identify patients at high risk of readmission and provide support to lessen the likelihood of readmission.

More information: CMAJ, www.cmaj.ca/lookup/doi/10.1503/cmaj.150100

Provided by Canadian Medical Association Journal

Study reveals flaws in gene testing; results often conflict

This stylistic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). The chromosome is X-shaped because it is dividing. Introns are regions often found in eukaryote genes that are removed in the splicing process (after the DNA is transcribed into RNA): Only the exons encode the protein. The diagram labels a region of only 55 or so bases as a gene. In reality, most genes are hundreds of times longer. Credit: Thomas Splettstoesser/Wikipedia/CC BY-SA 4.0

The first report from a big public-private project to improve genetic testing reveals it is not as rock solid as many people believe, with flaws that result in some people wrongly advised to worry about a disease risk and others wrongly told they can relax.

Researchers say the study shows the need for consumers to be careful about choosing where to have a gene test done and acting on the results, such as having or forgoing a preventive surgery.

"We have very clear documentation that there are differences in what patients are getting" in terms of how tests on the same gene variations are interpreted, said the study leader, Heidi Rehm, genetics lab chief at Brigham and Women's Hospital in Boston.

When deciding to get tested, either through a doctor's office or by sending in a swab to a private company, "patients need to choose labs that are sharing their data" with the broader research community so scientists can compare and learn from the results and make testing more accurate for everyone, she said.

Dozens of companies now offer gene tests to gauge a person's risk of developing various disorders. One of the newest tests on the market costs $250 and checks about 20 genes that can affect breast cancer risk.

But not all gene mutations, or variants, are equal. Some raise risk a lot, others just a little, and some not at all. Most are of unknown significance—a quandary for doctors and patients alike. And most variants are uncommon, making it even tougher to figure out which ones matter and how much.

To solve these mysteries and give patients better information, the U.S. government several years ago helped form and fund ClinVar, a database for researchers around the world to pool gene findings, coded to keep patients' identities confidential. More than 300 labs contribute to it, including universities such as Harvard and Emory and some private companies such as Ambry Genetics and GeneDX.

On Wednesday, the group made its first report at a conference in Washington. The study also was published online by the New England Journal of Medicine.

So far, the project has tracked more than 172,000 variants in nearly 23,000 genes, a small portion of the millions known to exist but some of the more common ones that have been identified.

More than 118,000 of these variants have an effect on the risk for a disease—and 11 percent have been analyzed by more than one lab so results can be compared. In 17 percent of those cases, labs interpreted the findings differently, as either raising the risk of a disease, having no effect on it or having an unknown effect.

At least 415 gene variants now have different interpretations that could sway a medical decision, such as whether to have healthy breasts or ovaries removed to lower the risk of cancer, or to get a medical device such as an implanted defibrillator to cut the risk of sudden cardiac death.

"The magnitude of this problem is bigger than most people thought," said Michael Watson, executive director of the American College of Medical Genetics and Genomics, one of the study's authors and a partner in the data pooling project.

And it can harm patients. Rehm described a woman who had genetic testing and wrongly was told she did not have elevated risks for breast cancer. She later developed the disease but could have had preventive surgery had the right gene analyses been done.

An independent expert, Dr. Eric Topol, director of the Scripps Translational Science Institute in La Jolla, California, commended the study leaders and the database project for "cleaning up the mess" from labs that have not shared data in the past.

"We need millions of people sequenced, sharing all the data," to make things better, he said. With more sharing, the mystery gene variant problem " will largely go away, but that's going to take a few years at least."

Cognitive impairment predicts worse outcome in heart failure

Cognitive impairment predicts worse outcome in elderly heart failure patients, reveals research presented today at Heart Failure 2015 by Hiroshi Saito, a physiotherapist at Kameda Medical Centre in Kamogawa, Japan. Patients with cognitive impairment had a 7.5 times greater risk of call cause death and heart failure readmission.

26 may 2015--Heart failure patients with cognitive impairment may get progressively worse at adhering to medications, leading to poorer prognosis.

Heart Failure 2015 is the main annual meeting of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and takes place 23 to 26 May in Seville, Spain.

Mr Saito said: "Systematic reviews have shown that cognitive impairment is common in patients with chronic heart failure. However, the impact of cognitive impairment on the prognosis of heart failure patients is not known. Our study investigated whether cognitive impairment independently predicted the outcome of elderly patients with heart failure."

The study retrospectively included 136 patients aged 65 years or over with heart failure who were admitted to Kameda Medical Centre. The Mini Mental State Examination (MMSE) was conducted to evaluate the presence of cognitive disorder in all patients before discharge. Patients were divided into two groups: those with cognitive disorder (score below 27 on the MMSE) and those without (score 27 or above).

Patients were 82 years old on average and 47% were men. According to the MMSE, 101 patients (74%) had cognitive disorder. After a follow up of 161 days, 33 patients (24%) were readmitted due to heart failure or died.

The researchers found that the prognosis of patients in the cognitive impairment group was significantly worse than the non-cognitive impairment group. They also showed that cognitive impairment predicted a 7.5 times greater risk of worse prognosis in elderly patients with heart failure. The risk remained even after adjusting for other prognostic factors including age, gender, body mass index, albumin, haemoglobin, brain natriuretic peptide (BNP), C-reactive protein (CRP), ejection fraction, estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN).

Mr Saito said: "Our study shows that cognitive impairment is common in elderly patients with heart failure, occurring in three-quarters of patients. We also found that cognitive impairment is an independent predictor of worse prognosis in elderly heart failure patients, who had a 7.5 times greater risk of all cause death or heart failure readmission."

He added: "We expect that heart failure patients with cognitive impairment tend to get progressively worse at adhering to medications. It is possible that this could explain why they have a worse prognosis. Cardiologists and other medical staff should assess the cognitive status of elderly heart failure patients."

Mr Saito continued: "When cognitive status is impaired we should provide education on disease management to families to prevent heart failure readmission of their loved ones. The three major components of this are medication, nutrition, and exercise. Of these three components, medication is an especially important element. It is necessary for families to enhance medication adherence for patients who are unable to manage their medication by themselves."

He concluded: "There are no specific treatments for cognitive impairment in heart failure patients. If patients do not have shortness of breath resulting from their heart failure, we often recommend mild exercise such as walking to maintain their cognitive function. Clinicians need to be more aware of the cognitive status of their heart failure patients and families can play an important role in ensuring that patients take their medication, get some exercise and eat well."

More information: The scientific programme is available here.

Provided by European Society of Cardiology

Orange juice could help improve brain function in elderly people

Drinking orange juice could help improve brain function in elderly people, according to new research from the University of Reading.

25 may 2015--The study saw a group of 37 healthy adults (mean age 67 years) consuming 500ml (just under a pint) of orange juice, daily over an eight week period. At the beginning and end of the eight weeks their memory, reaction time and verbal fluencywas measured. These were then combined into one overall score known as 'global cognitive function'.

The adults showed an 8% overall improvement in global cognitive function after orange juice consumption compared to a control drink (matched for taste and calories) given during a different eight week period. Although subtle, these improvements are significant. 

One of the tests of verbal memory required learning a list of words which are then recalled immediately and after a 30 minute delay. An 8% improvement equates to remembering one more word from a shopping list of 15 items. Small improvements such as this over an eight week period could translate into substantial improvements over the lifespan. 

While the researchers are not recommending that people drink 500ml of orange juice every day, they believe these findings show that the constituents of orange juice could play an important role in providing brain-boosting nutrients as part of a healthy, balanced diet. They also wish to reinforce the importance of being aware of the nutritional content of fresh fruit juice drinks, relative to daily recommended intake of sugar.

Dr Daniel Lamport, from the University's School of Psychology and Clinical Language Sciences and co-author of the study, said: "The population is ageing rapidly across the world. Estimates suggest that the number of persons aged 60 or over could triple by 2100. It's therefore imperative that we explore simple, cost-effective ways to improve cognitive function in old age."

Orange juice is a major source of a group of naturally occurring plant phytochemicals known as flavonoids, being particularly rich in a sub-class of flavonoids, known as flavanones. Recent studies from the School of Chemistry, Food and Pharmacy have shown that flavonoids may improve memory through the activation of signalling pathways in the hippocampus, a part of the brain that is associated with learning and memory. 

This study is thought to be one of the first to show that regularly consuming orange juice flavanones could have a positive effect on older people's cognition.

Dr Lamport continued: "Small, easily administered changes to the daily diet, such as eating more flavonoid-rich fruits and vegetables, have the potential to substantially benefit brain health. We know that people find it difficult to sustain big changes to their diet but simple alterations are much easier to maintain permanently.

"More research on the positive effects of flavonoids on cognition is still needed. However, this is an important discovery which strengthens the growing body of evidence that flavonoid rich foodstuffs could play a big role in tackling cognition decline in old age."

Previous Reading research has shown that other flavonoid rich foods such as blueberries are beneficial for cognition. Research is still ongoing to determine the exact mechanisms by which flavonoids may exert benefits to the brain. Several mechanisms have been proposed such as improved blood flow in the brain and protecting neurons against oxidative damage and increasing the efficiency with which neurons transmit signals.

More information: "Chronic consumption of flavanone-rich orange juice is associated with cognitive benefits: an 8-wk, randomized, double-blind, placebo-controlled trial in healthy older adults." Am J Clin Nutr 2015 ajcn.088518; First published online January 14, 2015. DOI: 10.3945/ajcn.114.088518

Provided by University of Reading

Depression associated with five-fold increased mortality risk in heart failure patients

Moderate to severe depression is associated with a 5-fold increased risk of all cause mortality in patients with heart failure, according to research presented today at Heart Failure 2015. The results from OPERA-HF show that risk was independent of comorbidities and severity of heart failure. Patients who were not depressed had an 80% lower mortality risk.

24 may 2015--Heart Failure 2015 is the main annual meeting of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and takes place 23 to 26 May in Seville, Spain.

Professor John Cleland, chief investigator of OPERA-HF and professor of cardiology at Imperial College London and the University of Hull, UK, said: "Patients with heart failure are at high risk of recurrent hospital admissions and death. Approximately 25% of patients admitted to hospital with heart failure are readmitted for a variety of reasons within one month. Within one year, most patients will have had one or more readmissions and almost half will have died."

He added: "OPERA-HF was designed to investigate in a more holistic fashion than previously the predictors of and reasons for readmission and death amongst patients with heart failure. This included social, mental and physical frailty, as well as comorbidities and the severity of heart failure. Depression has been reported to predict death in patients with heart failure but until now it was thought that this could be because depressed patients have more severe heart failure and more comorbidities."

OPERA-HF is an ongoing observational study enrolling patients hospitalised with heart failure. Depression was assessed using the Hospital Anxiety and Depression Scale (HADS-D) questionnaire and comorbidity was examined using the Charlson Comorbidity Index (CCI).

The results of the HADS-D questionnaire showed that 103 patients were not depressed (score 0-7), 27 had mild depression (score 8-10) and 24 had moderate to severe depression (score 11-21). Over a mean follow up of 302 days, 27 patients died.

Patients with moderate to severe depression had a 5-fold increased risk of death compared to those with no or mild depression. Moderate to severe depression remained an important predictor of all-cause mortality even after controlling for sex, age, hypertension, severity of heart failure (assessed by NT-proBNP) and comorbidities. Patients with a low HADS-D score (0-7) had an 80% lower risk of death.

Professor Cleland said: "Our results show that depression is strongly associated with death during the year following discharge from hospital after an admission for the exacerbation of heart failure; we expect that the link persists beyond one year. The association was independent of the severity of heart failure or the presence of comorbidities."

He added: "We know that depression is common in heart failure and affects 20-40% of patients. Depression is often related to loss of motivation, loss of interest in everyday activities, lower quality of life, loss of confidence, sleep disturbances and change in appetite with corresponding weight change. This could explain the association we found between depression and mortality."

Professor Cleland continued: "As doctors we are members of a caring profession and should be sympathetic to our patients' plight but I am not in favour of immediately prescribing anti-depressants. Studies suggest that they are not effective in reducing depression in patients with heart failure. Clinicians should, however, screen patients with heart failure for depression and consider referring those affected for counselling."

He concluded: "Our research clearly shows a strong association between depression and risk of death in the year after discharge from hospital. Recognition and management of depression may reduce mortality for patients with heart failure. More research is needed to find out what clinicians and patients themselves can do to manage depression. Better treatments for heart failure, co-morbidities as well as depression itself may be required."

More information: The HFA White Paper "Heart failure: preventing disease and death worldwide" is available here: www.escardio.org/static_file/E… epaper-15-May-14.pdf

Provided by European Society of Cardiology

University of Oslo researchers confirm new mechanism for Alzheimer's disease

Microscopy of mouse brain. Red alzheimer plaque surrounded by green astrocytes. Credit: Prof. Jens Pahnke

Jens Pahnke and his team at the University of Oslo has recently published results in the prestigious scientific journal Brain showing that decreased removal of toxic peptides in the brain causes the onset and first clinical signs of Alzheimer's disease, rather than overproduction as has previously been assumed. This information can now be used to target specific genes to enhance their function in the brain of elderly or people at risk.

23 may 2015--World-wide, researchers try to discover the cause for sporadic Alzheimer's disease which comprises 99% of all Alzheimer's disease patients. Alzheimer's patients develop deposits of toxic peptides in the brain that lead to the destruction of the neuronal networks and to clinical signs of disorientation, memory loss, behavioural changes, and finally to death. By generating a transgene-free mouse model for the more common sporadic form of the disease, the Pahnke team produced results that support the hypothesis of insufficient removal of toxic metabolites in sporadic Alzheimer's disease. The model animals develop early signs of the disease after 1.5 years of age, precisely at the locations where the first changes appear in Alzheimer's patients.

Normally, human mutated genes are used to generate animal models of Alzheimer's disease. Pahnke and his colleagues used a method in which they destructed the function of two genes in the brain that are needed to excrete and digest the toxic Alzheimer's peptide amyloid-beta. This represents a new model enabling investigations without artificial overexpression of inherited Alzheimer's disease genes.

The Pahnke lab is internationally renowned for its discoveries of disturbed export mechanisms in sporadic Alzheimer's disease. The lab was recently moved to Norway after Jens Pahnke was appointed professor at the University of Oslo's Faculty of medicine. Pahnke's team has developed new treatment strategies based on clearance mechanisms at the brains vasculature. These treatments are highly effective in a subset of patients and are used in Germany, Switzerland, Austria, and the USA.

Recent developments of Pahnke and his collaborators aim on medicinal plants that produce ABC transporter-activating agents and can be easily applied as natural medication in patients. These innovative projects are now started in Oslo as the internationally leading centre for research on Alzheimer disease, ABC transporters, and medicinal plants.

More information: "Accumulation of murine amyloid-{beta} mimics early Alzheimer's disease." Brain 2015; DOI: 10.1093/brain/awv137

Provided by University of Oslo

COPD is independent risk factor for cardiovascular death, but not risk of stroke

Chronic obstructive pulmonary disease, or COPD, is associated with increased risk of dying from a cardiovascular disease such as heart failure or a heart attack, as well as diseases not associated with the heart. However, COPD is not by itself associated with increased likelihood of having a stroke or a systemic embolism, according to a new research study.

22 may 2015--Researchers from Duke University and the Mayo Clinic reached this conclusion after analyzing data from a large randomized trial of patients with atrial fibrillation, a condition that produces an irregular heartbeat. The trial, ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), compared the effectiveness of two anticoagulants—apixaban and warfarin—on reducing the risk of stroke or systemic embolism in these patients. A systemic embolism occurs when a clot formed in the heart travels to another part of the body and blocks blood flow; typically, this blockage occurs in the brain, causing a stroke, but systemic emboli can also travel to other organs or a person's extremities.

The researchers examined the data from the 18,206 patients, all with atrial fibrillation, enrolled in ARISTOTLE to explore the connection between COPD and stroke in this patient population. The researchers will present their data during ATS 2015 in Denver, May 15 to 20.

"Other studies have shown that COPD is an independent risk factor for cardiovascular disease, but what hadn't been studied was whether COPD was an independent risk factor for stroke, specifically among patients with atrial fibrillation," said Michael Durheim, MD, a pulmonary and critical care fellow at Duke. Atrial fibrillation is itself a known risk factor for stroke and systemic embolism because clots more easily form when blood is pumped irregularly by the heart.

In their analysis, Dr. Durheim and his colleagues found that COPD was present in 1,950 (10.8%) of the 18,134 patients for whom pulmonary disease history was available. Patients with COPD were older, more often men and more likely to be current or former smokers. They were also more likely to suffer from other diseases that would put them at higher risk for stroke, including coronary artery disease, a prior heart attack and heart failure.

After adjusting for these and other patient characteristics, COPD was not associated with increased risk of stroke or systemic embolism (adjusted HR 0.86 [95% CI 0.61, 1.21], p = 0.382). However, COPD was associated with increased mortality from all causes by 54 percent (adjusted HR 1.54 [95% CI 1.31, 1.82], p < 0.001), including both cardiovascular and non-cardiovascular death.

Dr. Durheim says that because COPD independently raises mortality in patients with atrial fibrillation, further studies are warranted to "elucidate the mechanisms" by which COPD contributes to increased mortality. The results of those studies, he adds, might change clinical practice.

Meanwhile, he notes one practical outcome of his study: the effect of apixaban compared with warfarin on stroke or systemic embolism did not differ between subjects with and without COPD (HR 0.92 vs 0.78, interaction p = 0.617). "The presence of COPD doesn't need to affect provider's choice of an anticoagulant," he says.

More information: Abstract 65465: Chronic Obstructive Pulmonary Disease is Associated with Increased Risk of Mortality Among Patients with Atrial Fibrillation: Insights from the ARISTOTLE Trial

Provided by American Thoracic Society

People with depression may be more likely to develop Parkinson's disease

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

People with depression may be more likely to develop Parkinson's disease, according to a large study published in the May 20, 2015, online issue of Neurology, the medical journal of the American Academy of Neurology.

21 may 2015--"We saw this link between depression and Parkinson's disease during over a timespan of more than two decades, so depression may be a very early symptom of Parkinson's disease or a risk factor for the disease," said study author Peter Nordström, PhD, at Umeå University in Umeå, Sweden.

The researchers also examined siblings, and found no link between one sibling having depression and the other having Parkinson's disease. "This finding gives us more evidence that these two diseases are linked," said Nordström. "If the diseases were independent of each other but caused by the same genetic or early environmental factors, then we would expect to see the two diseases group together in siblings, but that didn't happen."

For the study, researchers started with all Swedish citizens age 50 and older at the end of 2005. From that, they took the 140,688 people who were diagnosed with depression from 1987 to 2012. These people were then matched with three control participants of the same sex and year of birth who had not been diagnosed with depression, for a total of 421,718 control participants.

The participants were then followed for up to 26 years. During this time, 1,485 people with depression developed Parkinson's disease, or 1.1 percent, while 1,775 people, or 0.4 percent of those who did not have depression, developed Parkinson's disease.

Parkinson's disease was diagnosed an average of 4.5 years after the start of the study. The likelihood of developing Parkinson's disease decreased over time. People with depression were 3.2 times more likely to develop Parkinson's disease within a year after the study started than people who did not have depression. By 15 to 25 years after the study started, people with depression were about 50 percent more likely to develop Parkinson's disease.

People with more serious cases of depression were also more likely to develop Parkinson's disease. People who had been hospitalized for depression five or more times were 40 percent more likely to develop Parkinson's disease than people who had been hospitalized for depression only one time. People who had been hospitalized for depression were also 3.5 times more likely to develop Parkinson's disease than people who had been treated for depression as outpatients.

The link between depression and Parkinson's disease did not change when researchers adjusted for other conditions related to depression, such as traumatic brain injury, stroke and alcohol and drug abuse.

Provided by American Academy of Neurology

Cognitive improvements with active singing in dementia

20 may 2015—An active singing program can improve cognition and life satisfaction among individuals with dementia in an assisted living facility, according to a letter to the editor published in the April issue of theJournal of the American Geriatrics Society.

Linda E. Maguire, from the Johns Hopkins University in Baltimore, and colleagues examined the impact of active singing on measures of cognition and life satisfaction at an assisted living facility. Forty-five participants received three vocal music sessions per week (independent residents: 18 singers, nine listeners; dementia: nine singers, nine listeners).

The researchers found that independent residents had significantly higher scores than those with dementia on the mini-mental state examination (MMSE; P < 0.001). Among participants with dementia, there was a significant interaction between pre-and post-study MMSE scores of singers and listeners (P = 0.04). Initial scores were not significantly different, but at the end of the study, singers had significantly higher MMSE scores than listeners (P = 0.008). Similarly, initially, there was no significant difference in clock-drawing ability between listeners and singers, but after treatment, singers scored significantly higher (P = 0.009). Compared with listeners, singers (independent living and dementia groups) had significantly higher Satisfaction with Life Scale scores (P < 0.001).

"These data show that an active singing program, using an innovative approach, led to significant improvement in cognitive ability in individuals with dementia," the authors write.

More information: Abstract 

Study shows non-memory Alzheimer's symptoms more likely in younger people

Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

New research has shown that people with Alzheimer's may not always experience memory loss as their first symptom of the disease, with younger people more likely to have problems with judgement, language or visual and spatial awareness than older people. The study of 7,815 people – one of the largest of its kind to date – suggests a need for greater awareness of the different symptoms of Alzheimer's disease, the most common cause of dementia. Led by a researcher at UCL (University College London) and part-funded by Alzheimer's Research UK, the UK's leading dementia research charity, the research is published in the journal Alzheimer's & Dementia.

19 may 2015--Alzheimer's disease, which currently affects half a million people in the UK, causes the death of brain cells and leads to a range of symptoms, including problems with thinking and memory and changes in behaviour. While memory loss is a typical early symptom of Alzheimer's disease, some people can experience other, very different symptoms in the early stages of the disease. The researchers set out to investigate how a person's age might affect the first symptoms they experience, looking at both cognitive symptoms – problems with thinking skills – and behavioural symptoms.

The team analysed data from 7,815 people in the US National Alzheimer Coordinating Center (NACC) database, which includes records on people attending Alzheimer's disease centres across the US. Each participant had a diagnosis of Alzheimer's, and a record had been made of the symptoms they had first noticed in the early stages of the disease. The average age of the group was 75, with the youngest person aged 36 and the oldest aged 110.

Although memory loss was the most common first symptom in all age groups, the results showed younger people were more likely than their older counterparts to report 'non-memory' problems first – including difficulty with judgement or problem-solving, problems with language, or a loss of visual or spatial awareness. In people under 60, a quarter reported that their first symptom was not memory loss, while one in five people in their 60s first had symptoms other than memory loss. This number fell to one in ten for people in their 70s, and one in 15 for those 80 years or older.

When the researchers compared the people's first reported behavioural symptoms, they also found age differences. The most common behavioural symptom was apathy or withdrawal, but compared to older age groups, younger people were more likely to experience depression or other behavioural symptoms such as anxiety. In contrast, older people were more likely to have had psychosis, or no behavioural symptom at all, compared to those who were younger.

Dr Jo Barnes, Alzheimer's Research UK Senior Research Fellow at UCL and the study's lead author, said: "Our results highlight the many different ways Alzheimer's can affect the brain, causing problems with several different cognitive processes, not just memory. Brain imaging studies have suggested that the disease may be more likely to affect different parts of the brain in younger people, and this may help to explain some of the different symptoms seen in our study. Importantly, however, even in older groups not all people with Alzheimer's report memory loss as their first warning sign of the disease.

"An awareness of symptoms other than memory loss is vital for helping to diagnose Alzheimer's, particularly for those people whose early symptoms are not typical of the disease. Our findings suggest a need for doctors to use tests that do not solely or disproportionately focus on memory, but which also take into account some of the different ways that Alzheimer's can manifest."

Dr Eric Karran, Director of Research at Alzheimer's Research UK, said: "All too often Alzheimer's is thought of as being a disease characterised only by memory loss, but this study shines a light on some of the other distressing symptoms people with the disease can experience. A greater understanding of these symptoms could not only help people receive a diagnosis earlier, but could also aid public awareness of the disease and help improve support services. Further research to investigate why younger people are more likely to experience different symptoms in the early stages of Alzheimer's could provide useful insights into the disease. It's worth noting that some of the people in this study may have been wrongly diagnosed with Alzheimer's, and these results highlight the need to develop more accurate tests for the disease. If we are to find better ways of diagnosing Alzheimer's early and new ways to treat the disease, continued investment in research is vital."

More information: "Alzheimer's disease first symptoms are age dependent: Evidence from the NACC data set." Alzheimers Dement. 2015 Apr 24. pii: S1552-5260(15)00117-X. DOI: 10.1016/j.jalz.2014.12.007

Provided by Alzheimer's Research UK

30 minutes of physical activity six days a week linked to 40 percent lower risk of death in elderly men

Credit: George Hodan/public domain

Thirty minutes of physical activity—irrespective of its intensity—6 days a week is linked to a 40% lower risk of death from any cause among elderly men, finds research published online in the British Journal of Sports Medicine.

17 may 2015--Boosting physical activity levels in this age group seems to be as good for health as giving up smoking, the findings suggest.

The researchers base their findings on people taking part in the Oslo Study, which invited almost 26,000 men born between 1923 and 1932 for a health check in 1972-3 (Oslo I).

Some 15,000 agreed. Their height, weight, cholesterol and blood pressure were all assessed, and they were asked whether they smoked.

They were also asked to respond to a validated survey (Gothenburg questionnaire) on their weekly leisure time physical activity levels.

These were categorised as sedentary (watching TV/reading); light (walking or cycling, including to and from work for at least 4 hours a week); moderate (formal exercise, sporting activities, heavy gardening for at least 4 hours a week); and vigorous (hard training or competitive sports several times a week).

Some 6000 of the surviving men repeated the process in 2000 (Oslo II) and were monitored for almost 12 years to see if physical activity level over time was associated with a lowered risk of death from cardiovascular disease, or any cause, and if its impact were equivalent to quitting smoking.

During the monitoring period, 2154 out of the 5738 men who had gone through both health checks died.

The analysis indicated that less than an hour a week of light physical activity was not associated with any meaningful reduction in risk of death from any cause. But more than an hour was linked to a 32% to 56% lower risk.

Less than an hour of vigorous physical activity, on the other hand, was linked to a reduction in risk of between 23% and 37% for cardiovascular disease and death from any cause.

The more time spent doing vigorous exercise the lower the risk seemed to be, falling by between 36% and 49%.

And men who regularly engaged in moderate to vigorous physical activity during their leisure time lived five years longer, on average, than those who were classified as sedentary.

Factoring in that the risk of death from heart disease/stroke rises with age, made only a slight difference to the results.

Overall, these showed that 30 minutes of physical activity—of light or vigorous intensity—6 days a week was associated with a 40% lower risk of death from any cause.

The impact would seem to be as good for health as quitting smoking among this age group, suggest the researchers.

This is an observational study so no definitive conclusions can be drawn about cause and effect, and the researchers point out that only the healthiest participants in the first wave of the study took part in the second wave, which may have lowered overall absolute risk.

But the differences in risk of death between those who were inactive and active were striking, even at the age of 73, they suggest.

More effort should go into encouraging elderly men to become more physically active, with doctors emphasising the wide range of ill health that could be warded off as a result, conclude the researchers.

More information: Increases in physical activity is as important as smoking cessation for reduction in total mortality in elderly men: 12 years of follow up of the Oslo II study, British Journal of Sports Medicine, DOI: 10.1136/bjsports-2014-094522

Provided by British Medical Journal

Age-friendly communities essential to urban elders' well-being

The future of communities around the world will in large part be determined by the efforts to achieve a high quality of life for their older citizens, according to the latest issue of Public Policy & Aging Report (PP&AR), titled "Making a Home in the City: The Age-Friendly Community Movement." A total of seven articles argue that developing cities that meet the interests of all generations should be an important goal for economic and social policy.

16 may 2015--"The concomitant growth of cities and of an older population within those cities has come to generate a disjuncture between physical infrastructure and resident needs," states PP&AR Editor Robert B. Hudson, PhD. "Modern economic growth results largely from private sector investments and incentives which pay little heed to the concerns of vulnerable populations."

Age-friendly communities are designed to promote aging-in-place, which is the ability to live in one's own home and community safely, independently, and comfortably regardless of age, income, or ability level.

This PP&AR brings together analysts and activists who have struggled with how to promote ideas and initiatives to enhance the well-being of urban elders. The authors address the evolution of the age-friendly community movement, a present a review of four major age-friendly community initiatives, and conclude with a challenge to move beyond locally-based initiatives and to engage policymakers at the state and federal levels to galvanize the movement. Together these conceptual and empirical pieces provide a thorough review of what forms age-friendly communities may take, how they work on the ground, and what next steps should be considered.

Provided by The Gerontological Society of America

Host, heal thyself: Immune system self-organizes to minimize biological cost of pathogenic infections

Schematic of a statistical model of antigen recognition by the adaptive immune system. After infection, antigen a encounters immune receptor r at random with a rate λa(t). An encounter leads to a successful recognition with a probability fr,a that reflects the matching between a given antigen–receptor pair. 

15 may 2015—The adaptive immune system – a subsystem of the overall immune system – comprises specialized cells and processes that eliminate or prevent pathogen growth by using the experience of past infections to prepare its limited repertoire of specialized receptors to protect organisms from future threats. Recently, scientists at CNRS and Ecole Normale Superieure, Paris and the University of Pennsylvania developed a general theoretical framework from first principles that allowed them to predict the composition of receptor repertoires optimally adapted to minimize the biological cost of infections from a given pathogenic environment. Their theory predicts that the immune system will have more receptors for rare antigens; individuals exposed to the same infections will have largely different repertoires; and competitive antigen/receptor binding and selective amplification of stimulated receptors are key to creating optimal repertoires. Their findings explain how limited populations of immune receptors can self-organize to provide effective immunity against highly diverse pathogens, and moreover inform the design and interpretation of experiments surveying immune repertoires.

Researchers Thierry Mora and Aleksandra M. Walczak discussed the paper that they and their colleagues published in Proceedings of the National Academy of Sciences. "A great deal of very interesting theoretical work has been done on the problem of avoiding autoimmunity – that is, recognizing self-proteins – essentially viewing the immune system as a device for discrimination," Mora tells Medical Xpress. "We wanted to study the problem from a different perspective: As, in essence, introduced by Sir Frank Macfarlane Burnet's theory of clonal selection1, an adaptive immune system adapts to its pathogenic or antigenic environment. We wanted to see how far we could take the idea that the composition and diversity of the immune repertoire reflects that of the environment – in other words, the repertoire is an internal representation of its environment – aimed at minimizing the cost of infections to the tissues of the organism." In short, Mora says, this is one way to look at the complicated problem of the structure of immune repertoires.

This approach allowed the scientists to create a new framework that makes it unnecessary to explicitly model intracellular communication, cell differentiation, activation of cofactors, coordination of different cell types, the interaction with the innate immune system, and the full complexity of the recognition process. "Our goal was to make concrete predictions about adaptive immune repertoires that are general and not specific to one kind of cell type in specific conditions. While these features all play an important role in the functioning of real immune systems, we wanted to see what the essence was, what an optimal but simplified immune system would look like," Walczak points out. "We didn't want to concentrate on the fine details of repertoires, but rather took a step back and try to see what we could learn from global properties while still being realistic enough to make concrete statements about real immune systems – for example, the fact that two individuals in similar environments can have very different optimal immune repertoires." The scientists discovered that their assumption – that is, the system needs to minimize the cost of infection given a limited number of encounters – actually structures the repertoire.

At a high level, the scientists wanted their model to define an effective cost that could encompass and summarize all the aforementioned factors. They found that the surprisingly simple mathematical equation F_a(m) – a general cost function that measures the harm to an organism caused by non-recognition of a pathogen by the immune receptors associated with antigen a that have had m encounters with any pathogen. "Due to its phenomenological generality," Mora says, "there was no particular challenge in defining it – but we nonetheless considered several possible scenarios because there may be issues in deciding what its exact form and values should be." In short, F_a(m) describes how the harm effectively increases with the number of encounters.

"This is an approach that is common in physics, especially statistical physics," Walczak tells Medical Xpress, "where rather than describing the motion of all the particles that make up a gas, we write an effective equation of the state of the gas, or describe the change in the density distribution of the gas. In this study we do something similar: Since we know that there are many processes contributing to how harm increases with the number of infections, that it's impossible to describe them all, and that their detailed form does not really change the effect, we simply ask how we can describe their effect on the immune system. For example," she illustrates, "if the antigen population increases exponentially in real time – which seems like a sensible assumption seeing that non-inhibited pathogens will proliferate exponentially – and the harm to the organism increases with non-recognition also increases exponentially in real time. A simple calculation shows that this means F_a(m) will be linear in relation to the number of encounters."

At the same time, Walczak illustrates, it is easy to imagine that certain infections do not initially harm the organism, and/or that some do significant harm very quickly and then the harm saturates. In other words, one can imagine different costs – so because one can obtain the same effective cost from different molecular processes due to different instances of the infection, the researchers studied effective cost in different specific forms of this function.

"One of our predictions is that the optimal repertoires of two individuals sensing practically the same environment can be very different" Walczak continues. "The concrete position of the receptors in recognition space does not matter, as long as globally they tile antigenic space and provide good coverage. We showed that the immune system can find many optimal solutions to the same problem, so we should not be surprised if two individuals that live in the same conditions and are genetically close have very different repertoires." While these repertoires are optimal and thereby idealized, she notes, the scientists showed they are reached through traditional dynamics long considered when studying lymphocytes, or white blood cells in vertebrate immune systems.

"We also found that, in many situations, optimal repertoires cover the rare pathogens more thoroughly than we would have expected from just their frequency," Mora notes. "If a pathogen is, for example, 100 times more common than another, an adaptive immune system should probably not devote 100 times, but perhaps only 10 times, more resources."

The immune repertoire can self-organize to a state that minimizes cost and provides protection against infections via competitive evolution of receptor populations stimulated by antigens. 

The study's central finding is that limited populations of immune receptors can self-organize to provide effective immunity against highly diverse pathogens. "It's long been known that receptors and antigens are cross-reactive – that is, one receptor can recognize more than one pathogen and vice versa – which in principle allows the pathogenic space to be covered by a reasonably small number of receptors," Mora explains. "However, this does not have to be the case." Walczak notes that while the optimization problem they solve does not try to minimize the diversity of receptors, the optimal repertoires they found do have this limited diversity. "Cross-reactivity tells us that this is possible, but it being optimal surprised us."

The paper also reports that the fact that cross-reactivity (in which a receptor can bind to a variety of antigens) causes the optimal repertoire to fragment is related to the concept of limiting similarity due to competitive exclusion in ecological settings. "Cross reactivity eliminates the need for a unique receptor specific to each antigen – but only if the receptor can recognize the antigen," Walczak notes. "This means that different regions of the pathogen recognition space can have receptors and no receptors, respectively. In a way, it would be a waste to have receptors in places already covered by the cross-reactivity of other receptors." Their research demonstrates this by showing that tiling patterns emerge in the antigenic space as a result of repertoire dynamics in which receptors compete for antigens if one receptor "wins" another cannot be in the same place, a process similar to that found in ecology when species cannot live in the same niche. The organisms compete and one "wins," the other having to go elsewhere – a salient factor in speciation as the two groups evolutionarily diverge.

"Thanks to cross-reactivity," Mora adds, "it doesn't matter exactly where you put a receptor, as long as the entire antigenic space is covered – an observation related to stochastic hyperuniformity2,3 in disordered systems – that is, local randomness but global order."

The study's results follow from a tension between the statistics of pathogen detection, which favor a broader receptor distribution, and the effects of cross-reactivity, which tend to concentrate the optimal repertoire onto a few highly abundant clones. "There are two features that drive the form of the optimal repertoires," Mora explains. "On the one hand, it's important to protect yourself from the rare pathogens, not just the common ones - so you want to place receptors more or less evenly in recognition space. On the other hand, cross reactivity tells you that you do not have to put a receptor at every point of that space—you just have to space them out so there are no blind spots. It's these two properties that drive the form of the solution.

The paper also details the conceptual connection between the immune repertoire and ecological organization. "Since receptors divide and proliferate upon recognition of the antigens, the latter can be seen as resources on which the receptors thrive. Receptors recognizing the same antigens compete against each other – they belong to the same ecological niche, so to speak." Since each niche has limited capacity, only a few receptors may survive in each of them – a process known as competitive exclusion.

As described above, in order to achieve the tiling patterns of optimal repertoires receptors must compete for antigens. "One of the key results about optimal repertoires is that you want to protect yourself both from the rare antigens and the common ones – so resources must be distributed relatively evenly, depending on the details of how fast the cost grows with the number of unsuccessful encounters between receptors and antigen. Moreover, the system must keep the receptors that are good fits against common antigens from dominating. In terms of dynamics, this is achieved by a limited carrying capacity for each niche." Carrying capacity is the maximum population size of a given species that an environment's resources can sustain indefinitely without significantly depleting or degrading those resources.

Within this ecological context, the paper notes that living systems must often sense, internally represent, and respond to salient aspects of complex exogenous influences – and do so using limited resources, such as cell types or genes. For example, in the retina2 and the mammalian olfactory system3 the limited repertoire of resources constrains information processing, forcing these living systems to judicially parse resources in terms of priorities, costs and limitations in order to adapt to the environment. The scientists comment that they "have shown that these elements also shape the optimal form of the immune repertoire."

The scientists assumed that although the immune system cannot predict precisely which antigens it will encounter and when, it incorporates an estimate of the probabilities of their occurrences. "While the immune system cannot know with certainty when and what it will encounter, its goal is to protect us from the unknown," Walczak points out. "It's also very hard to characterize the set of pathogens because the space is just too big. However, if the set of potential threats was completely random from the point of view of the repertoire, the immune system would not be very efficient." In other words, the fact that the immune system is able to respond efficiently suggests that it has adapted to a specific environment, which in turn translates into it incorporating an estimate of the probabilities of the antigenic environment.

Moving forward, the scientists would like to measure recognition space by testing their predictions in high-throughput surveys of receptor and pathogen diversity. "In order to do this," Walczak comments, "we'd need to figure out how to map the sequence of receptors to recognition or affinity, or measure affinity in a high-throughput way." (Affinity measures the strength of interaction between an epitope – the part of an antigen recognized by the immune system – and an antibody's antigen binding site.)

The researchers expect that the new framework and their results will extend to other distributed protection systems where diverse threats are addressed by an array of specific responses. "Yes," Walczak agrees, "the framework is very general, which is why, as discussed, we see very similar properties in systems as diverse as ecology, neuroscience and the physics of disordered systems." In addition, the immune system of bacteria, or the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system could be studied within a similar framework to predict the relative abundance of CRISPR spacers and corresponding viruses in a coevolving population of bacteria and viruses. "There's a tradeoff between a large number of threats/impulses and limited resources/processing abilities – and the immune system wants to minimize the chances of missing a threat/signal – and in our paper, she says, we've formalized this idea and made concrete predictions."

In addition to the connections with ecology, neuroscience and the physics of disordered systems discussed above, the study's results also inform the design and interpretation of experiments surveying immune repertoires. "There's a lot of interest in how different individuals – that is, either humans or genetically identical mice – respond to the same antigenic environments, and how different their natural repertoires are," Walczak says. "Our results show that it should not be surprising that the responses can be different, because even if their repertoires were optimal, two individuals would have different repertoires."

"Our predictions are about similarity in an effective recognition space," Mora concludes. "Most large scale probing of immune repertoires is based on sequencing the receptors – so mapping recognition space to receptor sequences is an important challenge for future experiments."

More information: How a well-adapted immune system is organized, Proceedings of the National Academy of Sciences (2015) published online before print, DOI:10.1073/pnas.1421827112