New World hemorrhagic fevers are emerging infectious diseases found in South America that can cause terrible, Ebola-like symptoms. Current treatments are expensive and only partially effective.

Now, Howard Hughes Medical Institute (HHMI) researchers have discovered exactly how one type of New World hemorrhagic fever virus latches onto and infects human cells, offering a much-needed lead toward new treatments.

“New World hemorrhagic fevers are nasty, serious, and often fatal diseases,” says Stephen C. Harrison, an HHMI investigator at Harvard Medical School and senior author of the report, published March 7, 2010, in Nature Structural & Molecular Biology. “The need for new interventions is high.”

Arenaviruses, the infectious agents that cause New World hemorrhagic fevers, circulate naturally in rodents and can infect people who are in close contact with the animals. Symptoms include severe inflammation and bleeding from the mouth, nose, eyes, and other orifices. Most outbreaks occur in rural regions of Bolivia, Venezuela, Argentina, and Brazil. “The outbreaks of New World hemorrhagic fever tend to be brief and brutal, with mortality rates of 20 to 30 percent,” says Jonathan Abraham, an M.D./Ph.D. candidate at Harvard University and first author of the paper. “These viruses aren’t a huge public health issue yet, but you could say the New World hemorrhagic fevers are an emerging disease threat.”

Researchers have known about these viruses since the 1960s, but the molecular basis of the disease has only been tackled recently, says Abraham, whose graduate studies are funded by HHMI through a Gilliam Fellowship for Advanced Study. The Gilliam Fellowships program currently supports the doctoral education of 30 exceptional students from disadvantaged backgrounds.

In 2007, Abraham was working with Boston Children’s Hospital virologist Hyeryun Choe when he was co-first author on a report in Nature identifying the human cell surface receptor that the Machupo virus, an arenavirus, grabs to gain access to the human cell it is infecting. The receptor, called transferrin receptor 1, offers a handhold for Machupo virus as it invades cells in the body. Nearly every human cell displays the transferrin receptor, which ferries iron into cells.

Abraham then brought the project to Harrison, who had mentored the young scientist in 2004 as part of HHMI’s Exceptional Research Opportunities Program (EXROP), which places undergraduate students from disadvantaged backgrounds in the laboratories of HHMI investigators and HHMI professors. The pairing was fortuitous. In Choe’s laboratory, Abraham had developed methods to produce the Machupo virus surface protein, which links to the human transferrin receptor. Meanwhile, Harrison had stocks of purified transferrin receptor because he had previously worked to image the molecule and understood its molecular structure.

Together, the pair made batches of the Machupo surface protein bound to the transferrin receptor and then set about creating an image showing how the two molecules connected. They used x-ray crystallography, a technique in which protein crystals are bombarded with x-ray beams. As the x-rays pass through and bounce off of atoms in the crystal, they produce a diffraction pattern, which can then be analyzed to determine the three-dimensional shape of the protein. After a data collection trip to the powerful x-ray beam at Argonne National Laboratory in Illinois, Abraham and Harrison were able to examine the atomic structure of the Machupo surface protein attached to the transferrin receptor.

The images show that the Machupo surface protein binds to the transferrin receptor in a surprising wayusing a loop called the apical domain. The biological function of this loop in humans is unknown, Harrison says. Other segments of the receptor bind iron-bearing transferrin, but the apical domain appears to be uninvolved in that process. “We don’t know the normal function of the apical domain. Obviously it didn’t evolve just to give Machupo virus a way to infect humans, but that’s what the virus has evolved to latch onto,” he says.

Because the apical domain is not involved in the critical task of moving iron into cells, Harrison says it presents an attractive target for drugs. In theory, an antibody designed to attach to the apical domain would prevent the Machupo virus from attaching to cells, blocking infection. One possible treatment strategy, then, would be to infuse patients with such an antibody during the early stages of infection, which might slow the infection enough to let patients recover.

Harrison says the finding might also help virologists predict which of the 22 known arenaviruses might be capable of infecting humans. Only five are known to infect humans nowand all of those bind to the human transferrin receptor. Presumably the other 17 viruses produce surface proteins that are unable to bind to the human transferrin receptor, Harrison says.

For Abraham, the idea of finding a treatment for these New World hemorrhagic fevers is close to his heart. His family hails from Haiti, where there is a “huge burden of infectious diseases. I’d like to dedicate my career to studying pathogens in underserved parts of the world,” he says.

Altered mental status describes a disorder of impaired cognition, diminished attention, reduced awareness or an altered consciousness level. Ten to 50 percent of hospitalized patients will experience acute altered mental status which accounts for a significant portion of neurological inpatient consultation.

In the study, the neurology researchers describe two cases in which both patients were admitted to the hospital (medical sick for different reasons) after a period of poor eating for more than a week. The first patient was put on high-protein dietary supplements three times daily on day three of his stay. By day five, this patient had slowed cognition and an unsteady gait requiring assistance. The patient’s ammonia level had doubled from baseline but his liver function tests were normal. Typically, patients exhibiting high ammonia levels present with liver disease but this patient had no history of it. On day seven the high-protein supplements were discontinued and within 24 hours his symptoms disappeared.

The second patient was also put on high-protein dietary supplements three times daily on day three. By day six, her family noticed that she seemed confused and would fall when walking. On day seven, her supplements were discontinued. She too had high ammonia levels but normal liver function tests and had no history of liver disease. Within 24 hours of stopping the supplements, her mental status, ability to walk and ammonia levels had returned to normal. Both patients resumed a regular diet with normal protein intake and returned to normal activity after hospital discharge.

After excluding for other causes, the researchers concluded that the confused mental status and high levels of ammonia in the blood were due to introducing high amounts of protein too quickly into the patients’ diet after weeks of poor eating.

“When an altered mental status occurs in the inpatient setting, many possible causes are considered. However, in these two medically complex patients, the initiation of high-protein dietary supplements was probably discounted, if even noticed,” said senior author Michael Perloff, MD, PhD, a fourth year resident in the department of neurology at BUSM. “With advances in nutritional education and supplements, this syndrome likely occurs thousands of times per year in hospitals across the United States. We believe it may account for more than 10,000 hospital days, countless morbidity and even some mortality,” added Perloff.

Funding for this study was provided by the Boston University Department of Neurology Residency Education Fund.

TITLE: Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance

AUTHOR CONTACT:
Isabelle Cremer
INSERM U872, Centre de Recherche des Cordeliers, Paris, France.
Phone: 33.1.44.27.90.83; Fax: 33.1.40510420; E-mail: isabelle.cremer@crc.jussieu.fr.

View this article at: http://www.jci.org/articles/view/36551?key=055913a0375e802e2994

“Clearly, investigators in this field are innovative, and progress is being made on several fronts in understanding the molecular and cellular changes causal of nervous system neoplasm and developing new therapies,” writes Roger N. Rosenberg, M.D., of the University of Texas Southwestern Medical Center, Dallas, and editor of the journal, in the editorial.

The theme issue focusing on cancers of the nervous system is being published in conjunction with a JAMA theme issue on cancer. The March issues of Archives of Pediatrics & Adolescent Medicine, Archives of Internal Medicine, Archives of Ophthalmology, Archives of Dermatology, Archives of Surgery, Archives of Facial Plastic Surgery and Archives of OtolaryngologyHead & Neck Surgery will also publish articles on this theme.

Articles in Archives of Neurology highlight the following topics, among others:

• Increased melanoma risk among Parkinson’s disease patients
• Differences between brain tumors that cause seizures and those that do not
• Identifying cancer-related neurologic complications
• New insights into the risk of glioma, a brain or nervous system tumor
• New therapies for glioblastoma, a common and aggressive type of brain tumor
• Lymphoma in the central nervous system

“We are grateful to our colleagues for providing a rich and varied clinical and research experience with these articles to give a perspective and in-depth appreciation of the dynamic and vital development that the field of neuro-oncology has undergone in recent years,” Dr. Rosenberg concludes. “The future looks positive and hopeful that continued progress will be made, especially in developing effective new therapies.”

(Arch Neurol. 2010;67[3]:272. Available pre-embargo to the media at www.jamamedia.org.)

Editor’s Note: Please see the articles for additional information, including author contributions and affiliations, financial disclosures, funding and support, etc.

TITLE: Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model

AUTHOR CONTACT:
Jadwiga Jablonska
Helmholtz Centre for Infection Research, Braunschweig, Germany.
Phone: 4953161815110; Fax: 4953161815002; E-mail: jja@gbf.de.

View this article at: http://www.jci.org/articles/view/37223?key=39e734818cb8f194020f

INDIANAPOLIS The gene for a newly recognized disease has been identified thanks to the determination of an Amish father and the clinical skills and persistence of Indiana University and Riley Hospital for Children physicians in collaboration with physicians and researchers at the Clinic for Special Children in Lancaster County, Penn., which specializes in disorders of the Amish.

The identification of the new multisystem autoimmune disorder and the recessive gene that causes it have been published early online and are reported in the 12 March 2010 print issue of the American Journal of Human Genetics.

The quest began when Jean P. Molleston, M.D., examined a young Amish boy whose family was looking for answers to why the child was not growing well, was developmentally delayed, had chronic diarrhea, and looked different from other children. In spite of numerous medical tests, which confirmed an enlarged liver and spleen, the cause of his multiple medical problems went undefined.

The search gained impetus for Dr. Molleston, an IU School of Medicine professor of pediatrics and Riley Hospital gastroenterologist, when a younger sibling was born with the same characteristics. Shortly thereafter, it also was recognized that a young cousin had similar problems.

Dr. Molleston and her colleagues had three cases and they reached out to Eric Puffenberger, Ph.D., Kevin Straus, M.D., and Holmes Morton, M.D., at the Clinic for Special Children, an innovative clinic dedicated to the unique needs of the Amish which employs cutting edge technology to search for genetic disorders. Blood samples and medical data on the children were sent for analysis. There experts were able to determine that an area of chromosome 20 was abnormally prominent in all three boys but not in unaffected children.

At this time Dr. Molleston and then IU School of Medicine pediatric resident Naomi Lohr, M.D., with the help of the father of the first child, conducted field screening in rural northeastern Indiana to search for additional affected children. Meanwhile, the Lancaster County team learned of a fourth child with similar problems who had multiple autoimmune disorders as had several of the Indiana children. Soon they were aware of a total of ten (7 boys and 3 girls) Amish children, with the oldest in his early twenties, who had the unrecognized multisystem disease. All the children were Indiana Old Order Amish (although some no longer lived in Indiana) and were related.

“It was recognizing autoimmune problems, including autoimmune hepatitis and lung and thyroid problems, that led us to focus our efforts to determine that the responsible gene was one identified as ITCH, one of 250 genes in the region of chromosome 20 identified by the Clinic for Special Children team,” said Dr. Molleston.

“We found that all the affected children had a mutation in ITCH, a gene which helps in ubiquination, the chaperoning or transporting of proteins around the cell. Ubiquination tells proteins where to go and what to do and it’s particularly important in damping down the immune system so it’s not overactive. Ubiquitination has many other important roles in the body’s cells, possibly explaining some of the other problems these children have,” she elaborated.

“Now that the gene has been identified and we are aware of several autoimmune diseases involved, the heavy lifting of identifying and helping these children can begin. We hear often from the father who brought the first child to us. As we all do, he hopes that now that we have identified the gene, we can quickly find effective treatment. But there are a lot of things going on in this disease and it’s going to take much more research to find what’s wrong with these children, whether environmental or other as yet unidentified factors contribute, and ultimately to develop drugs to affect ITCH without harming the children,” she said.

In addition to Dr. Molleston, who is the corresponding author of the paper, co-authors of “Human ITCH E3 Ubiquitin Ligase Deficiency Causes Syndromic Multisystem Autoimmune Diseases” are Naomi J. Lohr, M.D., formerly with the IU School of Medicine and now at the University of Colorado at Denver; Wilfredo Torres-Martinez, M.D., and Oscar W. Cummings, M.D., of the IU School of Medicine; Kevin A. Strauss, M.D.; D. Holmes Morton, M.D.; Erik G. Puffenberger, Ph.D.; Eric A. Sherman and Nicolas L. Rider, D.O. of the Clinic for Special Children; Robert H. Squires, M.D., of the Children’s Hospital of Pittsburgh; and Kudakwashe R. Chikwava, MBChB, of the Children’s Hospital of Philadelphia.

The IU School of Medicine and Riley Hospital are located on the campus of Indiana University-Purdue University Indianapolis.

ESMO Conference on Sarcoma and GIST

New breakthrough treatments for the most common cancers could soon come from cutting-edge research into some of the world’s rarest tumors.

At the ESMO Conference on Sarcoma and GIST, to be held in Milan, Italy, on 9 and 10 March 2010, researchers and some of the world’s leading experts will discuss exciting new science on sarcomasa group of rare tumors found in muscle, blood vessels, deep skin tissues, nerves and the tissues around joints.

Although these cancers only affect a relatively small number of people, researchers say understanding them could have far wider ramifications.

“Because sarcomas have well-characterized molecular alterations, they are an ideal model for developing new therapies,” says conference Co-Chair Dr. Jean-Yves Blay. “Sarcomas represent models for the development of targeted therapies in cancer.”

This is a crucial period in sarcoma research, Dr. Blay said. “We are right in the middle of some breakthroughs. Novel treatments are now emerging for a large number of sarcoma types.”

“Building on a precise understanding of the molecular biology of these tumors collected over the last decades, it is now possible to develop novel treatments targeting the initial molecular alterations driving these tumors,” says Dr. Angelo Paolo Dei Tos, conference Co-Chair. “The aim of this meeting will be to understand these novel strategies for targeted agents in these tumors, with practical consequences in more frequent tumor types”.

“Sarcomas are currently under the spotlight because they lend themselves to be targeted by the newest anticancer drugs. Of course, such new therapies need to be used in a strategically appropriate way,” says conference Co-Chair, Dr. Paolo G Casali. “This requires a deep integrated approach, bringing together highly diverse areas of expertise, from molecular biologists to surgeons, from radiation therapists to medical oncologists. The strong, global faculty of this sarcoma conference reflects ongoing attempts to take up the challenge in this family of rare cancers.”

So far, researchers have identified around 50 different kinds of soft-tissue sarcomas. Each of them is rare, although together they affect about 30,000 people in Europe each year. They include GIST, or gastrointestinal stromal tumor, a type of sarcoma that starts in the wall of the gastrointestinal tract.

More than 360 specialists in sarcoma and GIST are attending the conference, which is organized by the European Society for Medical Oncology (ESMO) in cooperation with the Milan Istituto Nazionale Tumori, with the support of Conticanet, a EU-funded project for clinical research on connective tissue cancers in Europe, and Eurobonet, the first European network of excellence dedicated to bone tumors.

The conference will have a particular focus on the molecular and pathological bases of soft tissue sarcomas and GIST, aiming to give a perspective on the state of the art in medical treatment and what new approaches are coming.

Notes to Editors

Meeting venue

The ESMO Symposium on Sarcoma and GIST will take place in Milan, Italy on 9 and 10 March. The meeting venue is the Starthotels Rosa, which is located near the city center (Piazza Fontana 3, 20122 Milan).

Services for media representatives

Journalists have the possibility to schedule one-on-one interviews with speakers, both in person and remotely. Please contact the ESMO Communication Dept. at media@esmo.org to book a telephone interview or to register to attend the meeting.

The conference full program is available at http://www.esmo.org/events/esmo-conference-on-sarcoma-and-gist-2010/program.html

About the European Society for Medical Oncology (ESMO)

The European Society for Medical Oncology (ESMO) is the leading European non-profit, professional organization for medical oncology promoting multidisciplinary cancer treatment around the world.

ESMO unites medical oncologists and other oncology specialists, healthcare professionals, caregivers, patients, policy-makers and all the key stakeholders in a global alliance committed to eradicating cancer and ensuring equal access to high quality treatment for all patients. Through state-of-the-art education and training programs, ESMO plays an instrumental role in providing the oncology community with the most up-to-date scientific research and information available. ESMO is dedicated to educating and supporting oncologists, optimizing patient care, disseminating cancer-specific information to the public, and advocating patient rights. As an authoritative voice in the fight against cancer, ESMO provides both the platform and the consultative expertise to influence national and international organizations as well as European authorities, in order to establish common standards for a multidisciplinary approach to cancer treatment. Through its flagship journal, Annals of Oncology, ESMO publishes articles on all aspects of clinical oncology.

To find out more about ESMO please visit www.esmo.org

About CONTICANET

CONTICANET is a European network of excellence entirely dedicated to connective tissue tumors of the soft part and viscera, working hand in hand with the twin partner Eurobonet itself dedicated to bone sarcomas. Seeking to promote a better understanding of these rare tumors, and to harmonize and optimize their treatment on the European level, the CONTICANET network is especially committed to the characterization of novel molecular entities, identification of the mechanisms of oncogenesis, organizing annotated tumor banks, preclinical testing, and clinical investigations of novel agents and local treatment options, all this in partnership with patients’ associations, and with the aim to promote novel standards of treatment and management of tumors, with ESMO.

To find out more about CONTICANET please visit http://www.conticanet.eu/html/

About EuroBoNet

EuroBoNet is the first European Network of excellence dedicated to bone tumors seeking to integrate research among top notch bone sarcoma referral centers. Integration and optimization of technical platforms, diagnostic expertise and research skills represent the backbone of the consortium.

To find more about EuroBoNet please visit http://www.eurobonet.eu

About the Istituto Nazionale per lo Studio e la Cura dei Tumori

The Istituto Nazionale Tumori, Milano, is the largest cancer clinical research institute in Italy, with more than 400 beds in service and 250 staff clinicians, as well as over 300 experimental oncology personnel. While its history dates back to 1928, more than 13,000 in-patients are currently admitted each year, and more than 800,000 out-patient visits are carried out. Forty percent of patients come from outside the Lombardy region. All the more, the institute serves as a national referral center for adult soft tissue sarcomas, with more than one thousand patients seen for consultation each year, and 250 undergoing surgery of localized sarcomas. It coordinates the ‘Italian Network on Rare Tumors,’ a national effort aimed at improving quality of care on rare adult solid tumors in Italy, through distant patient-sharing on a nationwide basis. Mainly through its active links with the Italian Sarcoma Group and the EORTC Soft Tissue and Bone Sarcoma Group, the Istituto Nazionale Tumori has been involved in most of the major clinical studies performed on adult soft tissue sarcomas and GIST in Europe over the last decades, and also provided several original contributions to basic and translational research as well.

To find out more about the Istituto Nazionale per lo Studio e la Cura dei Tumori please visit www.istitutotumori.mi.it

Led by Mark Davis, Ph.D., and Atul Butte, M.D., Ph.D., of Stanford University, Calif., the team of investigators received support from the National Institute of Allergy and Infectious Diseases (NIAID), as well as the National Heart, Lung, and Blood Institute and the National Cancer Institute, all part of the National Institutes of Health. Details about their work appear online at Nature Methods.

“Defining the status of the human immune system in health and disease is a major goal of human immunology research,” says NIAID Director Anthony S. Fauci, M.D. “A method allowing clinicians to accurately and quickly characterize the many different immune cells in human blood would be a valuable research and diagnostic tool.”

Over the past 15 years, the technology for gene expression microarrays, which allow investigators to identify and measure relative amounts of many different genes in parallel, has advanced tremendously. Today researchers can measure nearly every gene in the human genome using very small amounts of blood. However, blood contains numerous types of immune cells, such as lymphocytes, basophils and monocytes, and when microarray analysis is performed on this mixture, the interpretation of the results becomes problematic.

“Current methods that examine gene expression differences in mixtures of immune cells in blood do not take into account that, even among healthy individuals, there is a wide range of variation in the proportion of each cell type,” says Dr. Davis. “This creates so-called noise that masks many differences in gene expression. Even when you do observe a difference, you do not know if this is due to a real difference or a reflection of the varying number of cell types in the mixture.”

Until now, scientists had to separate out the cell types from a mixture prior to analysis to verify that actual changes in gene expression had occurred. But cell separation is time-consuming and costly, and requires large samples of blood, Dr. Davis adds.

To overcome such obstacles, the study team developed a computational approach called cell specific significance analysis of microarrays (csSAM).

“What csSAM does is marry the concepts of cell separation with the ease of analyzing large families of genes on a microarray,” explains Dr. Butte. “Using a mathematical approach, we can virtually separate out the different cell types found in blood, determine the gene expression patterns of these cell types, and identify which changes in gene expression are due to actual disease and which are simply due to variations in the cell proportions.”

Investigators first tested the csSAM approach using liver, brain and lung cells from rats. They began by analyzing the gene expression patterns in the three separate cell populations. Then they mixed the cells together in different known ratios and used the new mathematical approach to pick out the individual gene expression patterns of each cell subset in each mixture. Once they had confirmed that this analytical approach correctly identified the gene expression patterns of each individual cell subset in the mixtures, they tested csSAM on blood from kidney transplant patients who were either undergoing kidney rejection or who were stable.

Using a traditional approach to analyze the gene expression from blood, the investigators did not observe any differences between people undergoing transplant rejection and people with stable transplants. However, using the csSAM approach, they were able to pull out and measure from the mixture the gene expression patterns of five specific subsets of immune cellsmonocytes, basophils, neutrophils, eosinophils, and lymphocytes, known as T and B cells. The researchers were able to identify more than 300 differences in monocyte gene expression between the two groups and more than 100 genes that were significantly increased. Because monocytes make up a smaller proportion of immune cells in the blood, compared to neutrophils or lymphocytes, the traditional analysis approach could not distinguish these differences in monocyte gene expression amongst all the other gene signals.

Methods that separate out specific cell populations from blood can lead to changes in expression of genes that are not due to disease but to the experimental manipulations. The csSAM approach circumvents these additional measures that may create even more noise in the samples.

Another advantage of the csSAM approach is that it could be applied to other high-throughput analyses of genes, proteins or other cellular products of any complex mixture of cells or tissues.

“In recent years, NIAID has placed increasing emphasis on supporting human immunology research, such as this study,” says Daniel Rotrosen, M.D., of NIAID’s Division of Allergy, Immunology, and Transplantation. “We are very encouraged that our investment has helped to develop this new analytical approach, which has the potential not only to define the parameters of the healthy human immune system, but also to help identify biomarkers of disease and develop more effective vaccines.”

NIAID conducts and supports researchat NIH, throughout the United States, and worldwideto study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at www.nhlbi.nih.gov.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The National Institutes of Health (NIH)The Nation’s Medical Research Agencyincludes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference: S Shen-Orr et al. Extracting cell-type-specific gene expression differences from complex tissues. Nature Methods DOI: 10.1038/nmeth.1439 (2010).

In an evaluation for Faculty of 1000, Robert Sapolsky highlights a study published in Nature which assessed how testosterone affects human behavior in a ‘pro-social’ situation an environment where it is beneficial for a person to help someone else.

In an ‘Ultimatum Game’, a ‘proposer’ is given power to decide how a sum of money is divided between him/herself and another player, ‘the decider’. The decider can either accept the offer, and possibly receive less than a fair share, or reject it,in which case both players get nothing. The participants in the game were all women.

Women who were given testosterone unknowingly made fairer offers (a pro-social decision) than women who received a placebo. Interestingly, women who believed that testosterone has anti-social, aggression-causing effects and who thought they’d received testosterone made offers that were less fair, even when they had received a placebo.

When given to the subject in a blind trial, testosterone can encourage pro-social as well as anti-social behaviour. However, as the authors note, “biology seems to exert less control over human behavior [than in other animals],” since awareness of having received testosterone drastically altered behavior.

So, not only can our own behavior be confounded by our prejudices but the effects of testosterone may be far more complex than previously thought. As Sapolsky says, “Despite the seeming power of the proposer, the decider ultimately has the most power, and the proposer seriously loses status if the decider rejects their offer.”

Notes to Editors

1 Robert Sapolsky, Faculty Member for F1000 Biology, is Professor of Neurology & Neurological Sciences Stanford School of Medicine. http://f1000biology.com/about/biography/1858635299890760

2 The full text of the evaluation of is available free for 90 days at: http://www.f1000biology.com/article/2tj1y0f6mqncc4s/id/2127958

3 The free full text of the original paper by Eisenegger et al., Prejudice and truth about the effect of testosterone on human bargaining behavior, is available at: http://www.nature.com/nature/journal/v463/n7279/full/nature08711.html

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The most effective treatment for aortic stenosis, a common heart condition that shows with angina, loss of consciousness due to lack of blood flow, congestive heart failure, or sudden death, is valve replacement. However, large cohorts of people are never referred for this surgery because they are deemed too high-risk even though the prognosis is grim without the treatment.

New technologies such as stent-based transcatheter valve replacement can now be performed on high-risk patients without the need for sternotomy (an incision through the sternum), a heart-lung bypass machine or stopping the heart. Patients can also recover in a step-down unit compared with monitoring and treatment in an intensive care unit.

This procedure will benefit the 3% of the general population over 75 years of age that have severe aortic stenosis, a fixed obstruction, and in the future, could potentially treat lower risk patients such as in the 2% of the general population that have a defect called bicuspid aortic valves.

“Stent-based transcatheter value replacement now offers patients a less invasive alternative with potentially reduced risks, which may be particularly beneficial for elderly, high-risk patients,” write Dr. Michael W. A. Chu, Division of Cardiac Surgery, London Health Sciences Centre (London, Ontario) and coauthors.

Transcatheter valve replacements should be performed by an experienced, technologically adept team of cardiac surgeons, cardiologists and anesthesiologists.

The authors conclude that transcatheter heart valve replacement is still evolving, although the more than 10 000 devices implanted worldwide have helped establish success of the procedure. More information on long-term results is needed to determine the future evolution of these techniques.