Wednesday, December 23, 2009
antibiotic-resistant tuberculosis
Science Daily (December 23, 2009)
Tuberculosis Strain Thrives on Antibiotic
Scientists have identified a strain of antibiotic-resistant tuberculosis that thrives in the presence of rifampin, a front-line drug in the treatment of tuberculosis. The bacterium was identified in a patient in China and is described in a study by researchers at the Johns Hopkins Bloomberg School of Public Health, Chongqing Pulmonary Hospital, Lanzhou University and Fudan University. The researchers determined that the bacteria grew poorly in the absence of the antibiotic rifampin and better in the presence of the drug. They also observed that the patient's condition grew worse with treatment regimens containing rifampin, before being cured with rifampin-free regimens.
The World Health Organization (WHO) estimates that tuberculosis kills approximately 2 million people worldwide each year. Multidrug-resistant tuberculosis (MDR-TB) is becoming an increasing problem in many parts of the world, largely due to poor patient adherence to the six-month tuberculosis chemotherapy. About 5 percent of all TB cases are MDR-TB that is resistant to isoniazid and rifampin, two main drugs used to treat the disease.
"Rifampin-dependent tuberculosis is an unrecognized and potentially serious treatment issue," said Ying Zhang, MD, PhD, senior author of the study and professor in the Bloomberg School's W. Harry Feinstone Department of Molecular Microbiology and Immunology. "Rifampin resistance is ominous. Our study highlights the potential dangers of continued treatment of MDR-TB with rifamycins that occur frequently due to delayed or absent drug susceptibility testing in the field. Further studies are urgently needed to determine how common such rifampin-dependent MDR-TB is in field conditions and if it contributes to the worsening of the disease in MDR patients and treatment failures."
Zhang adds that rifampin-dependent tuberculosis is difficult to detect and may be a bigger problem than we currently realize, since the bacteria do not grow well in the culture medium unless rifampin is added. The study authors urge timely detection of rifampin-dependent or -enhanced bacteria in patients with treatment failure by including rifampin in culture media and removing of rifampin from the treatment regimen once rifampin dependency or enhancement are detected. However, the researchers note that drug susceptibility testing is time-consuming and not easily performed in resource-poor settings where tuberculosis is frequently more common.
For the study, the research team documented the treatment of a 35-year-old Chinese man with tuberculosis. The man failed to respond to the WHO's thrice-weekly treatment regimen, which includes rifampin and other first-line tuberculosis drugs. The patient's condition worsened following an additional treatment regimen with rifampin and other second-line agents. Further testing detected the rifampin-dependency/enhancement. The patient fully recovered once rifampin was removed from his treatment regimen.
Reference:
An interesting case of rifampicin-dependent/-enhanced multidrug-resistant tuberculosis.
Zhong, M.; Zhang, X.; Wang, Y.; Zhang, C.; Chen, G.; Hu, P.; Li, M.; Zhu, B.; Zhang, W.; Zhang, Y.
The International Journal of Tuberculosis and Lung Disease, Volume 14, Number 1, January 2010 , pp. 40-44(5)
Link to IJTLD abstract
severe fungal infections
Syracuse University News Service (December 22, 2009
New Compounds May Control Deadly Fungal Infections
An estimated 25,000 Americans develop severe fungal infections each year, leading to 10,000 deaths despite the use of anti-fungal drugs. The associated cost to the U.S. health care system has been estimated at $1 billion a year.
Now two Syracuse University scientists have developed new brominated furanones that exhibit powerful anti-fungal properties.
The most virulent fungus is Candida albicans, which is carried by about 75 percent of the public. Typically the fungus is harmless but, in individuals with HIV or otherwise compromised immune systems, it can cause candidiasis, which has a high mortality rate. The fungi can also form biofilms that attach to surfaces and are up to 1,000 times more resistant to anti-fungals.
"These new furanones have the potential to control such infections and save lives," says assistant professor Dacheng Ren of the Department of Biomedical and Chemical Engineering in SU's L.C. Smith College of Engineering and Computer Science. "In our tests, they reduced fungal growth by more than 80 percent, and we hope to improve on that going forward."
Ren and his collaborator, chemistry professor Yan-Yeung Luk of SU's College of Arts and Sciences, have filed a non-provisional patent application. They have also published related results in the Journal of Applied Microbiology and Biotechnology.
Over the past 20 years, pathogenic fungi have developed growing resistance to anti-fungal drugs. This stimulated a strong demand for more effective drugs and led to the successful research at Syracuse. The researchers' genomic study suggests that furanones have different genetic targets than current anti-fungal agents and thus may avoid drug resistance acquired in the past. The research team has also shown previously that these furanones inhibit bacterial biofilm formation; thus they may help control chronic infections where biofilms often appear, on surgical, dental and other implants.
Ongoing furanones research at Syracuse University will investigate a broad spectrum of other potential capabilities, ranging from diverse medical uses, such as controlling bacterial and fungal biofilms, to anti-fungal wood preservatives for the building materials market
reference
Inhibition of Candida albicans growth by brominated furanones
Miao Duo, Mi Zhang, Yan-Yeung Luk and Dacheng Ren
Journal of Applied Microbiology and Biotechnology 10.1007/s00253-009-2174-6
Link to JAMB abstract
Bird Flu
Science Daily (December 22, 2009)
Compound Found to Safely Counter Deadly Bird Flu
The specter of a drug-resistant form of the deadly H5N1 avian influenza is a nightmare to keep public health officials awake at night.
Now, however, a study published in the Proceedings of the National Academy of Sciences (PNAS) suggests that a new compound, one on the threshold of final testing in humans, may be more potent and safer for treating "bird flu" than the antiviral drug best known by the trade name Tamiflu.
Known as T-705, the compound even works several days after infection, according to Yoshihiro Kawaoka, a University of Wisconsin-Madison virologist and the senior author of the new study.
"H5N1 virus is so pathogenic even Tamiflu doesn't protect all the infected animals," explains Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine and a world authority on influenza. "This compound works much better, even three days after infection."
The Wisconsin research was conducted in mice and demonstrated that the compound was effective and safe against H5N1 virus, the highly pathogenic bird flu virus, which some scientists fear could spark a global epidemic of deadly influenza. The compound is also effective against seasonal flu and more worrisome varieties such as the H1N1 virus, and has already been tested against circulating seasonal influenza in humans in Japan where it is on the brink of Phase III clinical trials in people.
The prospect of a new front-line drug for influenza, in particular highly pathogenic strains such as H5N1 virus, is important as there are few drugs capable of checking the shifty influenza virus. The new study showing the efficacy and safety of T-705 assumes more importance as instances of Tamiflu-resistant strains of H5N1 virus have recently been reported, raising concerns about the ability of current antiviral drugs to blunt a pandemic of deadly avian flu.
Antiviral drugs are viewed as a readily available first line of defense against pandemic flu and are especially important for protecting health workers and others during an outbreak of disease. Vaccines, which utilize inactivated or weakened viruses to confer immunity, are the primary line of defense for influenza, but require months to formulate and mass-produce.
Aside from its safety and basic efficacy, another key trait of the T-705 compound is the fact that it is effective even after an infection is acquired. Bird flu, notes Kawaoka, is almost always diagnosed in the hospital after symptoms of the disease manifest themselves: "This compound has a chance to save people who have gone into the disease course," he says.
T-705 targets a critical viral molecule, polymerase, an enzyme that enables the virus to copy its genetic material, RNA. By disabling polymerase, the virus is unable to make new virus particles and maintain the chain of infection. Tamiflu, which remains an effective drug for blocking influenza virus, targets and regulates the enzyme neuraminidase, a protein found on the surface of the flu virus particle and that is essential for spreading the virus throughout the respiratory system.
"The activity of this agent is considerably higher than Tamiflu," says Kawaoka, adding, "the compound is very specific to viral polymerase. It doesn't affect host polymerase, which is important for safety and reducing side effects."
reference
T-705 (favipiravir) activity against lethal H5N1 influenza A viruses
Maki Kiso, Kazumi Takahashi, Yuko Sakai-Tagawa, Kyoko Shinya, Saori Sakabe, Quynh Mai Le, Makoto Ozawa, Yousuke Furuta, and Yoshihiro Kawaoka
Proceedings of the National Academy of Sciences (PNAS) December 14, 2009, doi:10.1073/pnas.0909603107
Link to PNAS abstract
Tuesday, December 22, 2009
Link between concurrency and HIV?
Roger Pebody for Aidsmap December 22, 2009
Concurrent sexual partnerships and the spread of HIV - ‘the evidence is limited’
The theory that multiple, overlapping sexual partnerships are a key driver of generalized HIV epidemics in Africa has been attacked as being based on insubstantial evidence. The critics, writing in the journals AIDS and Behavior and The Lancet, argue that researchers lack a precise definition of concurrency or a standard way to measure it, and that the data do not show a significant association between concurrency and either HIV incidence or prevalence.
However this critique has stimulated a fierce debate in the United States. Proponents of the concurrency thesis argue that the critics’ analysis of the data is selective, that evidence from a wide range of sources supports the thesis, and that it would be irresponsible for prevention programs in Africa to ignore this issue.
Concurrency
Concurrent sexual partnerships describe situations in which an individual has overlapping sexual relationships with more than one person. They can be contrasted with serial monogamy, when an individual has a sexual relationship with only one partner, with no overlap in time with subsequent partners.
A number of researchers, including Daniel Halperin, Timothy Mah and Martina Morris have suggested that concurrent relationships can increase the size of an HIV epidemic, the speed at which it infects a population and its persistence within a population.
The explanation for this is that in situations where a significant proportion of both men and women have concurrent relationships, even if they only have two partners each, as soon as one person in the network of concurrent relationship contracts HIV, then other people in the network are at risk (unless condoms are used). More people are more often exposed to the virus, including during the acute infection period when people are extremely infectious.
In contrast, in situations of serial monogamy, even if men and women have a relatively high number of sexual partners during their lifetime, one relationship is over before another is started. This means that if HIV is passed on within a relationship, it cannot be further transmitted as long as that relationship lasts.
Critique
Mark Lurie and Samantha Rosenthal argue that even if this theory is persuasive, empirical evidence for it is lacking. They call for better designed studies to clarify the contribution concurrency may make to generalized epidemics in Southern and Eastern Africa. Moreover, they believe that delivering prevention interventions around concurrency could be counter-productive and may divert resources away from other prevention methods that have proven efficacy.
Lurie and Rosenthal argue that concurrency is often vaguely and inconsistently defined. Some studies in fact collect data on total numbers of partners, and not concurrent relationships. Moreover, some include very brief or one-off liaisons (e.g. with a sex worker), but most do not.
Mah and Halperin, proponents of the concurrency thesis, accept that the lack of a consensus definition of concurrency or of a universally accepted method of measurement hampers comparison between studies.
They report a proposed standard definition from a UNAIDS working group: overlapping sexual partnerships where sexual intercourse with one partner occurs between two acts of intercourse with another partner.
The debate between Lurie and the other researchers focuses on the different type of research studies that may or may not demonstrate the contribution that concurrency makes.
The prevalence of concurrency in a population
A number of studies have taken a representative sample of a population to quantify the proportion of people who are participating in concurrent sexual relationships. These surveys show wide variation between different countries, with populations in sub-Saharan Africa tending to report much more concurrency than populations in other parts of the world.
Lurie and Rosenthal’s main criticism is that these studies simply cannot tell us anything about a link between concurrency and HIV.
In addition, they question the validity of comparisons between countries, given the variety of definitions used by researchers. They believe that there is no substantial evidence that levels of concurrency are significantly higher in Africa than elsewhere.
Lurie and the other authors tussle over the same studies. Referring to a review of sexual behavior in 59 countries, Lurie insists that it found that concurrency rates could not be compared and that African adults are less sexually active than adults in other regions. In contrast, Mah and Halperin provide the following quote from the same study: ‘‘Evidence is available that, although lifetime numbers of partners might be lower, concurrent relationships in men in some African countries might have been more common and of longer duration than in other regions’’.
Qualitative data
Whereas Mah and Halperin believe that qualitative research can demonstrate that concurrency is a highly normalized behavior in many parts of southern and eastern Africa and can help us understand its socio-cultural underpinnings, Lurie and Rosenthal dismiss qualitative research as inherently unrepresentative and prone to bias.
Individual studies
Only a few studies have compared individuals’ participation in concurrent relationships and their HIV status, and Lurie and Rosenthal note that a consistent relationship has not been found.
However Martina Morris, a leading researcher of concurrency, argues that such studies are “theoretically misguided and empirically irrelevant”. She says that concurrency is not a risk for the person who has more than one partner, but a risk for that person's partners. A monogamous partner may be exposed to HIV, not by his or her own behavior, but by the partner’s concurrency. Because of this, future studies will need to enroll partners.
Mah and Halperin also believe that concurrency increases an individual’s risk of transmitting HIV, not their risk of acquiring it. They point to studies from Uganda and Zimbabwe where HIV infection was associated with the belief that one’s partner was having concurrent relationships.
Population studies
In 2001, Lagarde and colleagues reported a study that used a standardized questionnaire to assess concurrency rates and HIV prevalence in five sub-Saharan cities. The study did not find that the two factors were correlated - for example, some lower prevalence cities had high rates of concurrency.
Lurie and Rosenthal cite this as a key study, but Martina Morris rejects the study design entirely. This is because HIV prevalence represents infections that have accumulated over many years, whereas the survey measured concurrency only in the previous year.
Mathematical modeling
Lurie and the proponents of concurrency all agree that the most powerful demonstrations of the influence of concurrency have come from simulation models. For example, Martina Morris and Mirjam Kretzschmar worked on Ugandan data and concluded that increasing the level of concurrency would have a more significant impact on epidemic spread than increasing the number of partnerships.
Lurie and Rosenthal say that even if these models show that concurrency can drive an epidemic, such theoretical work cannot demonstrate whether concurrency is actually doing so in Africa.
They also comment that other modeling studies, which found that the total number of partners or mixing between different social groups were more important than concurrency, tend not to be cited by the other authors.
In addition, in the articles published by Lurie and Helen Epstein, there is much claim and counter-claim as to the definitions used and the validity of the assumptions that were fed into the various modeling studies.
Conclusions
Mark Lurie and Samantha Rosenthal believe that the evidence base for the role of concurrency is weak and contradictory, and that better research with more refined definitions needs to take place before interventions to reduce concurrency can be delivered.
Morris counters that the studies Lurie and Rosenthal have looked at cannot prove or disprove the hypothesis. More sophisticated studies are being worked on and will give a more precise picture of concurrency’s role, “but no one argues that concurrency is irrelevant to transmission,” she says.
As such, she says it would be a “real tragedy” if methodological limitations were used to justify a do-nothing policy.
Mah and Halperin also argue that if HIV prevention interventions were never implemented until the most reliable evidence had been gathered, the only ones in use today would be male circumcision and interventions to prevent mother-to-child transmission. They believe that prevention messages which encourage people to have only one partner at a time are needed as one component of a prevention response.
References
Concurrent sexual partnerships and the HIV epidemics in Africa: evidence to move forward.
Timothy L. Mah & Daniel T. Halperin
AIDS and Behavior published online ahead of print,22 July, 2008 DOI 10.1007/s10461-008-9433-x.
Link to AIDS Behav abstract
Concurrent partnerships as a driver of the HIV epidemic in sub-Saharan Africa? The evidence is limited.
Mark N.Lurie & Samantha Rosenthal .
AIDS and Behavior published online ahead of print, 2 June, 2009. DOI 10.1007/s10461-009-9583-5
Link to AIDS Behav abstract
The evidence for the role of concurrent partnerships in Africa’s HIV epidemics: a response to Lurie and Rosenthal.
Timothy L. Mah & Daniel T. Halperin
AIDS and Behavior published online ahead of print, October 9, 2009 DOI 10.1007/s10461-009-9617-z
Link to AIDS Behav abstract.
The mathematics of concurrent partnerships and HIV: a commentary on Lurie and Rosenthal, 2009.
Helen Epstein
AIDS and Behavior published online ahead of print, 29 October, 2009 DOI 10.1007/s10461-009-9627-x.
Link to AIDS Behav abstract
Barking up the wrong evidence tree. Comment on Lurie & Rosenthal, “Concurrent Partnerships as a Driver of the HIV Epidemic in Sub-Saharan Africa? The Evidence is Limited”
Martina Morris
AIDS and Behavior published online ahead of print, 2009.
Link to AIDS Behav abstract
The concurrency hypothesis in sub-Saharan Africa: convincing empirical evidence Is still lacking. Response to Mah and Halperin, Epstein, and Morris.
Mark N. Lurie and Samantha Rosenthal
AIDS and Behavior published online ahead of print, 2009. DOI: 10.1007/s10461-009-9640-0
Link to AIDS Behav abstract
Concurrency driving the African HIV epidemics: where is the evidence?
Mark Lurie, Samantha Rosenthal, Brian Williams
The Lancet Volume 374: 1420 24 October, 2009 doi:10.1016/S0140-6736(09)61860-2
Link to The Lancet abstract
Concurrency driving the African HIV epidemics: where is the evidence? — Author's reply
James D. Shelton
The Lancet Volume 374: 1420 24 October, 2009 doi:10.1016/S0140-6736(09)61861-4
Link to The Lancet abstract
‘Tanning as a fashion trend’
Baylor University (December 21, 2009)
Adolescent Boys Seeking 'the Norm' May Take Risks With Their Appearances
— Teen-aged boys are more likely to use tanning booths, take diet pills and have their bodies waxed -- even if they think those activities are unhealthy -- if they are influenced by their peers, according to research by a Baylor University assistant professor of fashion merchandising.
Research also showed that boys ages 12 to 17 focused more on how their skin appears to others -- tone, texture and color -- than on other aspects of their appearance, including body shape, when they were influenced by peers, said Dr. Jay Yoo. His study has been awarded Best Paper in the psychological/social category by the International Textiles and Apparel Association.
The study will be published in fall 2010 in Adolescence, a quarterly international journal. Yoo studied 155 boys, with an average age of 14.3 years, in seven schools in the eastern United States.
"I studied what kids are teased about," Yoo said. "If anyone looks different, people tease you. Probably boys who have acne would become really self-conscious. There are cultural differences, but smooth skin is highly desired, and that may translate into other parts of the body.
"Skin tone also can represent the class of a person," Yoo said. "Skin that is dark brown or bronze is more ideal than pale. Tanning as a fashion trend is a relatively new phenomenon." While tanned skin once was associated with being blue collar, "a tan now is considered a sign of the leisure class," he said.
"As a result, the incident of skin cancers has risen dramatically over the past century."
Also, the availability of over-the-counter diet pills and media presentation of those products may make adolescents think taking them is the norm, Yoo said.
"They may view being slim as healthy, while being overweight is viewed as unhealthy. Taking diet pills is merely considered as a means to achieve slimness," he said.
He said the number of teen-age boys receiving spa services, such as hair removal, has nearly doubled since the early 1990s. Nearly half of the almost 14,000 spas in the United States compete for business by offering events and packages for teen-age boys, Yoo said.
"Boys used to use what was available in the bathroom cabinet," Yoo said. "But now it's aromatherapy and salon products, in which brand image as well as specific information are highlighted for adolescent consumers.
"I've heard a mother complaining about her son being teased in the locker room when he used to carry products that were not popular among his age group."
Peer influence is based on what adolescents observe as the norm, but also on advice or criticism from peers, Yoo said.
His findings about using a tanning booth, waxing skin and spa treatments suggest that appearance-conscious youths may share a wide range of information and experiences, he said.
"Until now, little research has been done about adolescents' appearance," Yoo said. But "adolescence is when they develop shopping patterns and appearance, and those who engage in risky behavior continue into adulthood."
Some of Yoo's findings about adolescent boy's perceptions of what is unhealthy behavior vs. their participation in those behaviors:
Activity: Perception as unhealthy-- Participation
- Using diet pills: 75.2 percent -- 4 percent
- Using tanning booths: 73.8 percent -- 9.4 percent
- Getting a tattoo: 67.6 percent -- 10.1 percent
- Body piercing: 66.7 percent --13.7 percent
- Dyeing hair: 63.4 percent --11.6 percent
- Sunbathing: 60.5 percent -- 27.7 percent
- Waxing skin: 51.7 percent -- 6 percent
Hormone that suppresses reproduction
Robert Sanders for U C Berkeley News (December 22, 2009)
New Human Reproductive Hormone Could Lead to Novel Contraceptives
Nearly 10 years after the discovery that birds make a hormone that suppresses reproduction, University of California, Berkeley, neuroscientists have established that humans make it too, opening the door to development of a new class of contraceptive and possible treatments for cancer or other diseases.
The hormone, gonadotropin inhibitory hormone (GnIH), has the opposite effect from gonadotropin releasing hormone, a key reproductive hormone. While GnRH triggers a cascade of hormones that prime the body for sex and procreation, GnIH puts a brake on the cascade.
"Identifying the inhibitory hormone in humans forces us to revise our understanding of the control mechanism of human reproduction," said first author Takayoshi Ubuka, a post-doctoral fellow in the UC Berkeley Department of Integrative Biology and in the Helen Wills Neuroscience Institute. "We hope this will stimulate clinical studies on people with precocious puberty or in the area of contraception."
Because reproductive hormones often promote the growth of cancer cells, GnIH might also work as an anti-cancer agent.
"Frequently, treatment of hormone-responsive cancers involves GnRH antagonists or very, very high doses of GnRH, which cause side effects," said George Bentley, UC Berkeley assistant professor of integrative biology. "Maybe we can use something that inhibits reproduction at physiological levels, so that we can bypass some of these side effects."
Ubuka, Bentley and their colleagues at UC Berkeley and in Japan and the United Kingdom report their findings in the Dec. 22 online issue of the public access journal PLoS ONE.
reference
Identification of Human GnIH Homologs, RFRP-1 and RFRP-3, and the Cognate Receptor, GPR147 in the Human Hypothalamic Pituitary Axis
Takayoshi Ubuka, Kevin Morgan, Adam J. Pawson, Tomohiro Osugi, Vishwajit S. Chowdhury, Hiroyuki Minakata, Kazuyoshi Tsutsui, Robert P. Millar, George E. Bentley
PLoS ONE 4(12): e8400. doi:10.1371/journal.pone.0008400
Link to PLoS ONE article
no sex – no malaria
BBC News on line (December 22, 2009)
Sex intervention combats malaria
It may be possible to combat malaria by interfering with the sex lives of the mosquitoes which spread the disease, according to scientists from The Imperial College London. They have shown that the insects can only mate successfully if the male is able to seal his sperm inside the female using a "mating plug". Without the plug, fertilization cannot occur, and they cannot reproduce.
The researchers focused on the species of mosquito primarily responsible for the transmission of malaria in Africa - Anopheles gambiae.
These insects mate only once in their lifetime, so disrupting the reproductive process offers a good way of dramatically reducing their numbers.
When they mate, the male transfers sperm to the female followed by a coagulated mass of proteins and seminal fluids known as a mating plug. This plug is not found in any other species of mosquito and its role had previously been unclear.
But the Imperial College team showed it was essential for ensuring sperm is correctly retained in the female's sperm storage organ, from where she can fertilize eggs over the course of her lifetime.
In the lab, the researchers were able to stop successful reproduction by preventing the formation of the plug in males.
Lead researcher Dr Flaminia Catteruccia said: "We have shown that the male mating plug is not a simple barrier to insemination from rival males, as has been previously suggested.
"Instead, we discovered that the plug plays an important role in allowing the female to successfully store sperm in the correct way inside her, and as such is vital for successful reproduction.
"Removing or interfering with the mating plug renders copulation ineffective. "This discovery could be used to develop new ways of controlling populations of A. gambiae mosquitoes, to limit the spread of malaria."
The researchers stopped the plug forming by knocking out a key enzyme which causes the seminal fluids to coagulate into a gelatinous solid mass.
Dr Catteruccia said: "If in the future we can develop an inhibitor that prevents the coagulating enzyme doing its job inside male A. gambiae mosquitoes in such a way that can be deployed easily in the field - for example in the form of a spray as it is done with insecticides - then we could effectively induce sterility in female mosquitoes in the wild.
"This could provide a new way of limiting the population of this species of mosquito, and could be one more weapon in the arsenal against malaria."
reference
Transglutaminase-mediated Semen Coagulation Controls Sperm Storage in the Malaria Mosquito
David W. Rogers, Francesco Baldini, Francesca Battaglia, Maria Panico, Anne Dell, Howard R. Morris, and Flaminia Catteruccia.
PLoS Biology, 7(12): e1000272. doi:10.1371/journal.pbio.1000272
Link to PLoS Biology article
Primer:Finding the Right Plugin: Mosquitoes Have the Answer.
Tracey Chapman
PLoS Biology, 7(12): e1000273. doi:10.1371/journal.pbio.1000273
Link to PLoS Biology primer
Monday, December 21, 2009
Hot spot
Researchers Attack British Medical Journal
Science Daily (December 21, 2009)
Conflict Over War Deaths: Researchers Attack British Medical Journal Review Process
Researchers from Canada, the UK and Sweden have slammed the influential British Medical Journal (BMJ) for publishing an error-filled study on global war deaths, refusing an equivalent rebuttal article and having a flawed peer-review process.
"This is not some trivial academic disagreement," says Andrew Mack, director of the Simon Fraser University-based Human Security Report Project (HSRP), which published a detailed critique of the BMJ's claims in the December issue of the Journal of Conflict Resolution (JCR).
"Accurate statistics on the health impacts of war are critically important not just for researchers but also for humanitarian organizations whose assistance programs save millions of lives around the world."
The HSRP article, "Estimating War Deaths: An Arena of Contestation," takes issue with a 2008 BMJ piece by Harvard researcher Ziad Obermeyer and colleagues, which rejected widely accepted battle-death statistics compiled by the International Peace Research Institute, Oslo (PRIO).
The PRIO data reveal that global war deaths declined by more than 90 per cent between 1946 and 2002.
But the BMJ claimed in a release publicizing the Obermeyer article that "war has killed three times more people than previously estimated and there is no evidence to support claims of a recent decline in war deaths."
Mack and HSRP study co-author Michael Spagat at the University of London, both leading experts on the subject, determined that the BMJ article failed to substantiate either assertion, was marred by serious mistakes and showed little understanding of the research it critiqued.
So Mack, the former strategic planning director to UN Secretary-General Kofi Annan, emailed the BMJ identifying six major methodological and factual errors in the Obermeyer article "Fifty Years of Violent War Deaths from Vietnam to Bosnia."
"The problems we point out would have been obvious to any of the many conflict researchers familiar with the research being criticized," says Spagat.
The U.K. journal acknowledged none of the errors, he says, and it ruled out publishing a detailed rebuttal, claiming the Obermeyer study was very thoroughly reviewed by appropriate experts.
"But the BMJ is well aware that its peer review process is flawed," says Spagat. "A recent study, whose authors include the journal's current editor, revealed that, on average, only a third of the 'major errors' deliberately inserted in a BMJ article were picked up by reviewers."
Adds Mack: "There appears to be no way of effectively rebutting BMJ articles that contain unwarranted -- and damaging -- critiques of the work of other scholars.
"This makes the journal effectively unaccountable by shielding it from serious criticism."
The JCR paper and technical appendix, PRIO battle deaths data, the BMJ paperBMJ peer review are all available on line and technical appendix, and a paper on the
Link to HSRP
References:
Estimating War Deaths: An Arena of Contestation.
Michael Spagat, Andrew Mack, Tara Cooper, Joakim Kreutz
Journal of Conflict Resolution, 2009; 53 (6): 934 DOI: 10.1177/0022002709346253
Link to JCR abstract
Fifty years of violent war deaths from Vietnam to Bosnia: analysis of data from the world health survey programme.
Ziad Obermeyer, Christopher J L Murray, Emmanuela Gakidou.
British Medical Journal, 2008; 336: 1482-1486 DOI: 10.1136/bmj.a137
Link to BMJ abstract
Bedside manner
Loyola University Health System news release (December 18, 2009)
Doctors' Bedside Skills Trump Medical Technology
Sometimes, a simple bedside exam performed by a skilled physician is superior to a high-tech CT scan, a Loyola University Health System study has found.
Researchers found that physicians' bedside exams did a better job than CT scans in predicting which patients would need to return to the operating room to treat complications such as bleeding.
"The low cost, simple, but elegant neurological exam appears to be superior to a routine CT scan in determining return to the operating room," researchers report in the Journal of Neurosurgery.
Patients typically receive CT scans following open brain surgery to remove tumors, repair aneurysms, treat brain injuries, etc. But practices vary. Some surgeons order CT scans right after surgery. Others wait until the following morning.
There are downsides. CT scans cost hundreds of dollars and expose patients to radiation. Transporting patients to scanning machines "involves multiple personnel of varying skills and nursing staff who are taken away from their other unit responsibilities," researchers wrote. "These scans also often interfere with work flow efficiencies of the radiology department."
The lead author of the study is Dr. Ahmad Khaldi, chief resident in the Department of Neurological Surgery at Loyola University Chicago Stritch School of Medicine. The senior author is Dr. Thomas Origitano, chairman of the Department of Neurological Surgery.
Researchers examined the records of 251 patients who received CT scans within 24 hours of surgery at Loyola. They included 133 patients who received routine scans within seven hours of surgery and 108 patients who received routine scans between 8 hours and 24 hours after surgery. None of the routine scans predicted which patients would need to return to the operating room.
Patients also received bedside neurological exams by physicians. In 10 cases, physicians detected serious problems, such as being slow to wake up, that warranted an urgent CT scan. Three of these urgent scans (30 percent) confirmed the patients' problems were serious enough to require a return to the operating room. By comparison, 0 percent of the 241 routine CT scans predicted whether patients would have to return to the emergency room.
A normal CT scan given right after surgery might give a doctor a false sense of security, which could lead to less frequent monitoring and neurological exams. Of the 14 patients in the study who took a serious turn for the worse, 13 had had CT scans within four hours of surgery that were normal or showed only minor problems.
"Scanning technology is really good," Origitano said. "But applying it without a physician's input is not necessarily helpful."
reference
The clinical significance and optimal timing of postoperative computed tomography following cranial surgery
Ahmad Khaldi, M.D., Vikram C. Prabhu, M.D., Douglas E. Anderson, M.D., and Thomas C. Origitano, M.D., Ph.D.
Journal of Neurosurgery 1-5.Posted online on 18 Dec 2009.
Link to JNS contents
Attorney density = MRSA?
Science Daily (December 20, 2009)
Fear of Lawsuits May Prompt Some Doctors to Overprescribe Antibiotics
A new study led by a team of researchers at New York Medical College suggests that that medical liability concerns may be playing a role in the increase of MRSA in healthcare settings by encouraging clinicians to prescribe antibiotics more often and more broadly than clinical circumstances and evidence-based guidelines warrant.
The study appeared in the September-October issue of the American Journal of Therapeutics.
The team analyzed census figures, statistics on population density of attorneys and physicians, and data on antibiotic utilization for the United States, Canada, and 15 European countries. They compared this to statistics on the percentage of methicillin resistance among clinical isolates of S. aureus. They found a strong correlation between the prevalence of methicillin resistance and density of attorneys in countries in Europe and North America. They found no correlation between prevalence of methicillin resistance and physician density.
Investigators surveyed 162 healthcare providers to determine whether medical liability concerns were as important as antibiotic cost and formulary restrictions in selecting treatment regimens. The surveys also confirmed that physicians were more concerned about medical liability in cases of under-prescribing antibiotics rather than by over-prescribing them.
George Sakoulas, M.D., assistant professor of medicine and lead author of the study, concluded, "The findings suggest that more research is needed to evaluate the potential impact of medical liability concerns on the medical care system. The study findings hint toward the importance of medical tort reform as a way to reduce healthcare costs and improve quality. Another way might be to foster more judicious prescription of antibiotics based on science and evidence rather than on risk aversion."
Reference:
Relationship Between Population Density of Attorneys and Prevalence of Methicillin-Resistant Staphylococcus aureus: Is Medical-Legal Pressure on Physicians a Driving Force Behind the Development of Antibiotic Resistance?
Sakoulas, George; Wormser, Gary P; Visintainer, Paul; Aronow, Wilbert S; Nadelman, Robert B.
American Journal of Therapeutics, 2009; September/October 2009 - Volume 16 - Issue 5 - pp e1-e6 DOI: 10.1097/MJT.0b013e3181727946
Linl to AJT abstract
Hydra helps?
Science Daily (December 20, 2009)
Antimicrobial Peptide from Ancient Organism May Be Effective Against Multiresistant Human Pathogens Including MRSA
Researchers in Germany have identified a new antimicrobial peptide that demonstrates significant activity against a variety of bacteria, including multiresistant human strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The discovery was made while investigating the ancient metazoan organism Hydra magnipapillata.
The researchers from Christian-Albrechts-University and the University Medical Center Schleswig-Holstein Campus, Kiel, Germany report their findings in the December 2009 issue of the journal Antimicrobial Agents and Chemotherapy.
While occurrences of multidrug-resistant infections continue to increase, the discovery and development of drugs effective against these bacterial strains have slowed. Once commonly thought of as a hospital-acquired infection, MRSA has now spread to the community (now known as community acquired or CA-MRSA) and is infecting previously healthy young people who have not been recently hospitalized or undergone a medical procedure. Past research has proven that ancient organisms are well equipped at preventing infectious pathogens from entering the body and given the desperate need for new drug targets, further exploration of these organisms is warranted.
MRSA has already developed resistance to CA-MRSA human antimicrobial peptides and prior studies have shown antibacterial immune responses in the simple metazoan Hydra magnipapillata to include bactericidal peptides with novel structural features and modes of action. In the study researchers identified the antimicrobial peptide arminin 1a from Hydra and found that it exhibited significant and wide-spread activity against bacteria including MRSA and enterococci, a common cause of nosocomial infections that is also drug-resistant. Further observations revealed that bacteria are killed when the bacterial cell wall is disrupted and the antibacterial activity of arminin 1a isn't affected by exposure to salt in human blood. Finally, researchers determined that arminin 1a doesn't share any ancestry with any known antimicrobial peptides.
"Our data suggest that ancient metazoan organisms such as Hydra hold promise for the detection of novel antimicrobial molecules and the treatment of infections caused by the multiresistant bacteria," say the researchers.
Reference:
Activity of the Novel Peptide Arminin against Multiresistant Human Pathogens Shows the Considerable Potential of Phylogenetically Ancient Organisms as Drug Sources.
René Augustin, Friederike Anton-Erxleben, Stephanie Jungnickel, Georg Hemmrich, Björn Spudy, Rainer Podschun, and Thomas C. G. Bosch.
Antimicrobial Agents and Chemotherapy, 2009; 53 (12): 5245 DOI: 10.1128/AAC.00826-09
Link to AAC abstract
Sunday, December 20, 2009
leprosy genes
Yahoo News covers the Tan Ee Lyn Reuters report from Hong Kong (December 16, 2009
Experts uncover genes that may be linked to leprosy
Genes may explain why some people are more susceptible than others to leprosy, according to an extensive study in China that found mutations of seven genes which appear to increase a person's susceptibility to leprosy, in sharp contrast to what experts have believed for a long time - that the disease is not congenital, or inherited.
"All along, people thought it was caused (only) by an infectious agent but our study found it is influenced by genetics. If a parent has the disease, it is highly likely that the child will develop the disease," one of the researchers Zhang Furen at the Shandong Provincial Institute of Dermatology and Venereology in northeast China said by telephone.
"What is interesting is that between couples, if one has the disease, the other remains uninfected for decades ... so how can this (strictly) be an infectious disease? Maybe this disease has to do with inheritability."
"What we found was that apart from the infectious agent, there is an internal reason, we found seven (susceptibility) genes ... it may have a lot to do with genetics (inherited susceptibility)," Zhang told Reuters.
The finding may have similar implications for other germs belonging to the family, like the bug that causes tuberculosis - which killed 1.8 million people last year.
The experts analyzed genes of 706 leprosy patients and 1,225 others without the disease, and mutant versions of the seven genes turned up consistently in those who had the disease. The participants were ethnic Chinese from eastern China.
Five of the genes appear to be involved in regulating the human immune system, said the researchers from China and Singapore.
"Leprosy has a long incubation period of 8 to 10 years, and once the symptoms surface, they would have caused the patient irreversible damage," Zhang said.
"But in future, if we can tell whether a person is susceptible to the disease before symptoms show, we can proceed to take preventive action."
reference
Genomewide Association Study of Leprosy
Fu-Ren Zhang, M.D., Ph.D et al.
New England Journal of Medicine December 16, 2009 (10.1056/NEJMoa0903753)
Link to NEJM article
earliest proven case of leprosy
Science Daily (December 16, 2009)
DNA of Jesus-Era Shrouded Man in Jerusalem Reveals Earliest Case of Leprosy
The DNA of a 1st century shrouded man found in a tomb on the edge of the Old City of Jerusalem has revealed the earliest proven case of leprosy.
The burial cave, which is known as the Tomb of the Shroud, is located in the lower Hinnom Valley and is part of a 1st century C.E.(Common Era) cemetery known as Akeldama or 'Field of Blood' (Matthew 27:3-8; Acts 1:19) -- next to the area where Judas is said to have committed suicide. The tomb of the shrouded man is located next to the tomb of Annas, the high priest (6-15 C.E.), who was the father in law of Caiaphas, the high priest who was said to have betrayed Jesus to the Romans. It is thus thought that this shrouded man was either a priest or a member of the aristocracy. According to Prof. Gibson, the view from the tomb would have looked directly toward the Jewish Temple.
No second burial
What is particularly rare about this tomb is that it was clear this man, which is dated by radiocarbon methods to 1-50 C.E., did not receive a secondary burial. Secondary burials were common practice at the time, where the bones were removed after a year and placed in an ossuary (a stone bone box). In this case, however, the entrance to this part of the tomb was completely sealed with plaster. Prof. Spigelman believes this is due to the fact that this man had suffered from leprosy and died of tuberculosis, as the DNA of both diseases was found in his bones.
Historically, disfiguring diseases -- particularly leprosy -- caused the afflicted individuals to be ostracized from their communities. However, a number of indications -- the location and size of the tomb, the type of textiles used as shroud wrappings, and the clean state of the hair -- suggest that the shrouded individual was a fairly affluent member of society in Jerusalem and that tuberculosis and leprosy may have crossed social boundaries in the first century C.E.
Disproves Turin Shroud?
This is also the first time fragments of a burial shroud have been found from the time of Jesus in Jerusalem. The shroud is very different to that of the Turin Shroud, hitherto assumed to be the one that was used to wrap the body of Jesus. Unlike the complex weave of the Turin Shroud, this is made up of a simple two-way weave, as the textiles historian Dr. Orit Shamir was able to show.
Based on the assumption that this is representative of a typical burial shroud widely used at the time of Jesus, the researchers conclude that the Turin Shroud did not originate from Jesus-era Jerusalem.
The excavation also found a clump of the shrouded man's hair, which had been ritually cut prior to his burial. These are both unique discoveries because organic remains are hardly ever preserved in the Jerusalem area owing to high humidity levels in the ground.
Social health in antiquity
According to Prof. Spigelman and Prof. Greenblatt, the origins and development of leprosy are largely obscure. Leprosy in the Old Testament may well refer to skin rashes such as psoriasis. The leprosy known to us today was thought to have originated in India and brought over to the Near East and to Mediterranean countries in the Hellenistic period. The results from the first-century C.E. Tomb of the Shroud fill a vital gap in our knowledge of this disease.
Furthermore, the new research has shown that molecular pathology clearly adds a new dimension to the archaeological exploration of disease in ancient times and provides us with a better understanding of the evolution, geographic distribution and epidemiology of disease and social health in antiquity.
The co-infection of both leprosy and tuberculosis here and in 30 percent of DNA remains in Israel and Europe from the ancient and modern period provided evidence for the postulate that the medieval plague of leprosy was eliminated by an increased level of tuberculosis in Europe as the area urbanized.
The molecular investigation was undertaken by Prof. Mark Spigelman and Prof. Charles Greenblatt of the Sanford F. Kuvin Center for the Study of Infectious and Tropical Diseases at the Hebrew University of Jerusalem, Prof. Carney Matheson and Ms. Kim Vernon of Lakehead University, Canada, Prof. Azriel Gorski of New Haven University and Dr. Helen Donoghue of University College London. The archaeological excavation was led by Prof. Shimon Gibson, Dr. Boaz Zissu and Prof. James Tabor on behalf of the Israel Antiquities Authority and the University of North Carolina at Charlotte.
Reference:
Molecular Exploration of the First-Century Tomb of the Shroud in Akeldama, Jerusalem. Carney D. Matheson, Kim K. Vernon, Arlene Lahti, Renee Fratpietro, Mark Spigelman, Shimon Gibson, Charles L. Greenblatt, Helen D. Donoghue
PLoS ONE, 4(12): e8319. doi:10.1371/journal.pone.0008319
Link to PLoS ONE abstract
Saturday, December 19, 2009
Little Boxes
Editorial: New Scientist (issue 2738 December 12 - 18, 2009
Time's up for psychiatry's bible
The American Psychiatric Association has announced that the publication of DSM-V will be delayed until May 2013. "Extending the timeline will allow more time for public review, field trials and revisions," says APA president Alan Schatzberg.
This does little to diminish the concerns raised by the editorial, which notes
Books are by and large riding out the online revolution that is devastating the sales of many newspapers, magazines and other printed works. But this week we report on a volume that has outlived its usefulness. The American Psychiatric Association (APA) is in the midst of rewriting the mammoth tome called the Diagnostic and Statistical Manual of Mental Disorders, or DSM, which provides checklists of symptoms that psychiatrists and other doctors use to diagnose what form of mental illness a patient has - and fights are breaking out all over.
The final wording of the new manual will have worldwide significance. DSM is considered the bible of psychiatry, and if the APA broadens the diagnostic criteria for conditions such as schizophrenia and depression, millions more people could be placed on powerful drugs, some of which have serious side effects. Similarly, newly defined mental illnesses that deem certain individuals a danger to society could be used to justify locking these people up for life.
Given such high stakes, we should all be worried by the controversy Proponents of some of the changes are being accused of running ahead of the science, and there are warnings that the APA is risking "disastrous unintended consequences" if it goes ahead with plans to publish DSM-V, as the new manual will be known, in 2012.
It doesn't have to be this way. With the advent of the internet, there is no longer any compelling need to rewrite the diagnostic criteria for the whole of psychiatry in one go. Yes, diagnoses should be revised as new scientific findings come in. But for this, specialists can be assembled when necessary to address specific areas that have become outmoded. Their suggestions can be posted on the web for comment. More research can be commissioned, if necessary. And when consensus is reached, new diagnostic criteria can be posted online.
Similarly, standing panels could periodically review issues that cut across the whole of psychiatry - such as the inevitable shift away from checklists of symptoms towards a system based on measurements of the underlying biological and psychological determinants of mental health.
The APA's leaders suggest that DSM-V will become a "living document" that will be amended as necessary. It's a shame they didn't simply move the current DSM into this mode. That would have hurt the APA's coffers, as a book that becomes a required reference is a big earner; DSM sales since 2000 exceed $40 million. But it's hard to see who else stands to gain from the current exercise - and if the critics' dire predictions come to pass, patients will be the biggest losers.
Link to New Scientist editorial
The editorial refers to Peter Aldhous’s article in the same New Scientist issue
Psychiatry's civil war
Two eminent retired psychiatrists are warning that the revision process is fatally flawed. They say the new manual, to be known as DSM-V, will extend definitions of mental illnesses so broadly that tens of millions of people will be given unnecessary and risky drugs.
Link to Psychiatry’s Civil War
The article is also illustrated with ‘flashpoint’ issues on "Transgendered" and "Bereavement" and
Hebephilia
How young is too young?
You may have never heard of "hebephilia", but this obscure diagnosis has huge significance in the courts. If it becomes accepted it could lead to hundreds of sex offenders who have served their jail time being locked up indefinitely - on grounds that some say are spurious.
Hebephilia refers to when adults are sexually fixated on teenagers around the time of puberty. This sets it apart from pedophilia, which refers to a focus on pre-pubescent children. The DSM-V work group on sexual disorders is likely to call for paedophilia to be renamed paedohebephilia, and include a hebephilic subtype.
The justification is the research of one work group member, Ray Blanchard of the University of Toronto. Working with sex offenders, Blanchard used a device that records blood flow in the penis to measure their arousal while they were listening to sexual material. He concluded that some men have a disorder that causes them to fixate on girls aged 11 to 14 (Archives of Sexual Behavior, vol 38, p 335).
The proposed diagnosis has been condemned by critics as dangerously blurring the boundary between pedophilia and normal male attraction to teenage girls - which isn't necessarily acted upon. Karen Franklin, a forensic psychologist in El Cerrito, California, argues that the diagnosis makes a disease out of preferences that have been shaped through human evolution. "People didn't used to live so long and mating started earlier," she says.
The work group is also considering whether some men are specifically turned on by rape - a proposed condition termed paraphilic coercive disorder. Again, the evidence is based largely on measurements of penile blood flow in response to sexual images and stories, and the validity of the condition is hotly contested.
The rows over hebephilia and paraphilic coercive disorder aren't academic, because 20 US states have passed laws that allow sex offenders who have served their sentences to be detained indefinitely in a secure hospital if they are deemed "sexual predators". This can only be done if the offenders have a psychiatric disorder that increases their risk of reoffending - which few do, according to DSM-IV.
Franklin says that if hebephilia and paraphilic coercive disorder make it into DSM-V, they will be seized upon to consign men to a lifetime of incarceration. This argument cuts little ice with Blanchard, however. "The clinical facts are what they are," he says.
Link to “Hebephilia” flashpoint [with NS links to studies cited]
Here in Washington State, the notion of the DSM as a "living document" comes as a little bit of an indictment to the Governess and the Mental Health ‘professionals’ who colluded to legislate and codify requirements based on part of the “fourth edition of the diagnostic and statistical manual of mental disorders, published in 1994”.
Not to worry, the process is almost complete (even if you haven’t actually heard about it ).
There seems to be a cottage industry growing in the provision of credentialing shops and ‘professional’ supervisors. Yes your shrink will have a supervisor – ‘the ghost in the room’ and guess who’s going to pay for that (not to mention all the increased fees and ‘continuing education' costs). Maybe there will be universal health coverage that works (and you won’t mind the loss of privacy).
Is it us or does it seem ironic that all this is still going on when the State has a deficit which requires to Governess to cut essential services. You could vent to your 'counselor' if they are still there!
"specialized and necessary for normal orthographic processing"
Science Daily (December 16, 2009)
How Do We Understand Written Language?
How do we know that certain combinations of letters have certain meanings?
Reading and spelling are complex processes, involving several different areas of the brain, but researchers from Johns Hopkins University have now identified a specific part of the brain -- named the left fusiform gyrus -- which is necessary for normal, rapid understanding of the meaning of written text as well as correct word spelling.
Dr Kyrana Tsapkini, from the Department of Neurology at Johns Hopkins University School of Medicine, and Dr Brenda Rapp, from the Department of Cognitive Science at Johns Hopkins University, studied the reading comprehension and spelling abilities of a patient who had undergone surgical removal of part of his brain due to a tumor. The patient's reading and spelling abilities had been above average prior to the surgery. They tested the patient and a group of control participants using 17 experimental tasks, which evaluated their comprehension and production of written language, spoken language, as well as their processing of other visual categories such as faces and objects.
The results of the study revealed that the patient was able to understand the meaning of spoken language as rapidly as the other participants and was similarly able to process objects and faces in a normal way. However, he showed significant delays in understanding the meaning of written text and also had difficulty in producing accurate spellings when writing dictated text, suggesting that these abilities required the use of the brain area, which had been removed.
According to the authors, the findings provide clear evidence that there are particular structures within this part of the brain -- the left mid-fusiform gyrus -- that are "specialized and necessary for normal orthographic processing."
Reference:
The orthography-specific functions of the left fusiform gyrus: Evidence of modality and category specificity.
Kyrana Tsapkini and Brenda Rapp
Cortex, 2009; DOI: 10.1016/j.cortex.2009.02.025
Link to Cortex abstract
Friday, December 18, 2009
‘a $9 billion cathedral of science’
Science Daily (December 15, 2009)
Large Hadron Collider Produces First Physics Results
The first paper on proton collisions in the CERN Large Hadron Collider (LHC) -- designed to provide the highest energy ever explored with particle accelerators -- is published online this week.
On 23 November 2009, during the early commissioning of the CERN (European Organization for Nuclear Research) LHC -- which was built in the circular tunnel of 27km circumference previously used by the Large Electron-Positron collider (LEP) -- two counter-rotating proton bunches were circulated concurrently for the first time in the machine, at the LHC injection energy of 450 GeV per beam.
A total of 284 collisions were recorded by the ALICE experiment (A Large Ion Collider Experiment) and immediately reconstructed and analyzed. The researchers determined the average number of charged particles emitted perpendicular to the beam direction, known as 'pseudorapidity density'. Their aim was to compare their results with previous measurements of proton-antiproton collisions at the same energy, and to establish a reference for comparison with future measurements at higher LHC energies.
The paper by the ALICE collaboration, which brings together authors from 113 research institutes, describes the experimental conditions in detail, as well as the main features of the ALICE detector systems used for the analysis.
The results obtained are consistent with earlier measurements of proton-antiproton interactions at the same energy. They also compare with model calculations.
Dr. Jürgen Schukraft from CERN and ALICE spokesperson said: "This important benchmark test illustrates the excellent functioning and rapid progress of the LHC accelerator, and of both the hardware and software of the ALICE experiment, in this early start-up phase. LHC and its experiments have finally entered the phase of physics exploitation."
Reference:
First proton–proton collisions at the LHC as observed with the ALICE detector: measurement of the charged-particle pseudorapidity density at √s=900 GeV
The ALICE Collaboration
The European Physical Journal C – Particles and Fields, December 2009; DOI: 10.1140/epjc/s10052-009-1227-4
Link to EPJC abstract
For a wider perspective, in Vanity Fair (January 2010 issue) read Kurt Andersen’s
The Genesis 2.0 Project
Compared with the market-driven, killer-app insta-culture of the Digital Age, the new Large Hadron Collider exists in a near-magical realm, a $9 billion cathedral of science that is apparently, in any practical sense, useless. Exploring its whizbang machinery, deep underground, the author probes the collider’s brush with disaster last year—and the secrets it may soon unlock.
Plus: photographs of the Large Hadron Collider by Todd Eberle
Gamers ‘fast and accurate’
Science Daily (December 18, 2009)
Video Games: Racing, Shooting and Zapping Your Way to Better Visual Skills
Do your kids want a Wii, a PlayStation or an Xbox 360 this year? This holiday gift season is packed with popular gaming systems and adrenaline-pumping, sharpshooting games. What's a parent to do? Is there any redeeming value in the hours that teens spend transfixed by these video games?
According to a new study in Current Directions in Psychological Science, a journal of the Association for Psychological Science, regular gamers are fast and accurate information processors, not only during game play, but in real-life situations as well.
In the study, psychological scientists from the University of Rochester, Matthew Dye, Shawn Green and Daphne Bavelier, looked at all of the existing literature on video gaming and found some surprising insights in the data. For example, they found that avid players got faster not only on their game of choice, but on a variety of unrelated laboratory tests of reaction time.
Many skeptics agree that gamers are fast, but that they become less accurate as their speed of play increases. Dye and colleagues find the opposite: Gamers don't lose accuracy (in the game or in lab tests) as they get faster. The scientists believe that this is a result of the gamer's improved visual cognition. Playing video games enhances performance on mental rotation skills, visual and spatial memory, and tasks requiring divided attention.
The scientists conclude that training with video games may serve to reduce gender differences in visual and spatial processing, and thwart some of the cognitive declines that come with aging.
Reference:
Increasing Speed of Processing With Action Video Games.
Matthew W.G. Dye, C. Shawn Green and Daphne Bavelier.
Current Directions in Psychological Science, 2009; Volume 18 Issue 6, Pages 321 – 326 DOI: 10.1111/j.1467-8721.2009.01660.x
Link to CDPS abstract
synthetic blood-clotting agent
BBC News on line (December 18, 2009)
Fake blood product for soldiers
Scientists from Case Western Reserve University say they have made a synthetic blood-clotting agent that could help wounded troops and patients. In the lab, the fake platelets cut bleeding in half compared with having no treatment.
They could offer doctors a limitless supply with a longer shelf life than fresh donor platelets and the US team in the hopes the product could become available in coming years.
The stuff the fake platelets are made from is already used in treatments approved by the US regulators, which the scientists say should help speed things along.
James Bertram and Professor Erin Lavik developed the platelets using biodegradable polymers and designed them to home in and link up with a patient's own platelets at the site of injury.
Natural blood platelets are good at helping wounds to clot but can be overwhelmed by large injuries.
Using donor platelets from other people can boost clotting but carries risks of complications, including rejection. And these fresh platelets must be refrigerated and have a shelf life of only five days.
The researchers' aim is to develop a treatment that medics can keep in their packs to treat wounded soldiers in the field.
Professor Lavik said: "This could be a complement to current therapies.
"The military has been phenomenal at developing technology to halt bleeding from external or compressible injuries.
"But so many injuries are from blast traumas where the damage is on the inside. And it can be hard to stop bleeds like this in the field."
She said the fake platelets could offer a viable solution and an immediate treatment before transfer to a field hospital.
In rats, injections of the therapy prior to injury halved bleeding time. When given 20 seconds after the injury, bleeding time was cut by a quarter.
To avoid the fake platelets clumping together and creating an artificial clot, each synthetic platelet is built with a surrounding water shield.
This also means that any surplus platelets not needed for the clotting should be flushed out of the body with no ill effects.
reference
Intravenous Hemostat: Nanotechnology to Halt Bleeding
James P. Bertram, Cicely A. Williams, Rebecca Robinson, Steven S. Segal, Nolan T. Flynn and Erin B. Lavik
Science Translational Medicine 16 December 2009: Vol. 1, Issue 11, p. 11ra22 DOI: 10.1126/scitranslmed.3000397
Link to Sci Trans Med abstract
Europe – HIV & Risk
Michael Carter for Aidsmap (December 17, 2009)
HIV prevalence and risk behavior varies between gay men in Southern and Eastern Europe
HIV prevalence is higher amongst gay men in Southern Europe than amongst gay men in Eastern Europe, according to an international study published in the December 3rd edition of Eurosurveillance.
Almost 17% of gay men in Barcelona were HIV-positive, according to the results of the study, compared to a prevalence of 3% in Prague.
However, the investigators also found high levels of risky sexual behavior amongst gay men in Eastern Europe and low frequency of HIV testing. “The potential for further HIV transmission in Eastern European cities is evident”, they comment.
There has been a marked increase in annual HIV diagnoses amongst gay men across Europe since 2000. Although some of these diagnoses can be attributed to increased levels of HIV testing, others are due to recent onward transmission of the virus. Indeed, other research has shown that significant numbers of gay men engage in sexual behavior that could involve a risk of contracting HIV.
To better understand the epidemiology of HIV amongst gay and other men who have sex with men, a team of investigators designed a study that involved 2241 individuals in six cities (Barcelona, Spain; Bratislava, Slovakia; Bucharest, Romania; Ljubljana, Slovenia; Prague, Czech Republic; and Verona, Italy). The study was conducted between 2008-09.
The study participants were recruited from the gay scene and all reported sex with another man in the previous twelve months. HIV prevalence was monitored using oral HIV tests. The men also completed questionnaires about their sexual risk behavior, drug use, and HIV testing history.
HIV prevalence was much higher in Southern Europe than in Eastern Europe. The prevalence of the infection amongst gay men in Barcelona was 17% and it was 12% in Verona. Bratislava had the highest HIV prevalence in Eastern Europe (6%), followed by Ljubljana and Bucharest (both 5%) and Prague (3%).
Levels of HIV testing were highest in Barcelona (56%), followed by Verona (53%), Bucharest (43%), Prague (42%), Ljubljana (38%) and Bratislava (32%).
Reported HIV risk behavior varied between the cities. The use of condoms with a casual partner was reported by 67% of men in Barcelona and by 36% of individuals in Prague. Condom use for anal sex was lower with regular partners, and was reported by 43% of men in Barcelona and Bucharest and by 20% of men in Bratislava.
Men in Barcelona and Verona had the highest number of reported casual partners (mean 16 and twelve respectively), with lower numbers reported by men in Eastern Europe (mean six – eight).
Alcohol was the most widely used drug in all cities, but other patterns of recreational drug use varied.
Reference
HIV bio-behavioural survey among men who have sex with men in Barcelona, Bratislava, Bucharest, Ljubljana, Prague and Verona, 2008-09.
M Mirandola, C Folch Toda, I Krampac, I Nita, D Stanekova, D Stehlikova, I Toskin, L Gios, J P Foschia, M Breveglieri, M Furegato, E Castellani, M G Bonavina, the SIALON network
Eurosurveillance, Volume 14, Issue 48, 03 December 2009
Link to Eurosurveillance article
Thursday, December 17, 2009
megathrust earthquakes?
Science Daily (December 16, 2009)
Tremors Between Slip Events: More Evidence of Great Quake Danger to Seattle
For most of a decade, scientists have documented unfelt and slow-moving seismic events, called episodic tremor and slip, showing up in regular cycles under the Olympic Peninsula of Washington state and Vancouver Island in British Columbia. They last three weeks on average and release as much energy as a magnitude 6.5 earthquake.
Now scientists have discovered more small events, lasting one to 70 hours, which occur in somewhat regular patterns during the 15-month intervals between episodic tremor and slip events.
"There appear to be tremor swarms that repeat, both in terms of their duration and in where they are. We haven't seen enough yet to say whether they repeat in regular time intervals," said Kenneth Creager, a University of Washington professor of Earth and space sciences.
"This continues to paint the picture of the possibility that a megathrust earthquake can occur closer to the Puget Sound region than was thought just a few years ago," he said.
The phenomenon, which Creager discussed during a presentation at the annual meeting of the American Geophysical Union, is the latest piece of evidence as scientists puzzle out exactly what is happening deep below the surface near Washington state's populous Interstate 5 corridor. He noted that the work shows that tremor swarms follow a size distribution similar to earthquakes, with larger events occurring much less frequently than small events.
The Cascadia subduction zone, where the Juan de Fuca tectonic plate dips beneath the North American plate, runs just off the Pacific coast from northern California to the northern edge of Vancouver Island in British Columbia. It can be the source of massive megathrust earthquakes on the order of magnitude 9 about every 500 years. The last one occurred in 1700.
The fault along the central Washington coast, where the Pacific and Juan de Fuca plates are locked together most of the time but break apart from each other during a powerful megathrust earthquake, was believed to lie 80 miles or more from the Seattle area. But research has shown that the locked zone extends deeper and farther east than previously thought, bringing the edge of the rupture zone beneath the Olympic Mountains, perhaps 40 miles closer to the Seattle area. It is this locked area that can rupture to produce a megathrust earthquake that causes widespread heavy damage, comparable to the 2004 Indian Ocean earthquake or the great Alaska quake of 1964.
Episodic tremor and slip events appear to occur at the interface of the plates as they gradually descend beneath the surface, at depths of about 19 to 28 miles. The smaller tremors between slip episodes, what Creager refers to as inter-episodic tremor and slip events, appear to occur at the interface of the plates a little farther east and a few miles deeper.
"There's a whole range of events that take place on or near the plate interface. Each improvement in data collection and processing reveals new discoveries," Creager said.
Episodic tremor and slip events often begin in the area of Olympia, Wash., and move northward to southern Vancouver Island over a three-week period, but scientists have yet to pin down such patterns among the smaller tremors that occur between the slip events.
Because the two tectonic plates are locked together, stress builds at their interface as they collide with each other at a rate of about 4 centimeters (1.6 inches) a year. The slip events and smaller tremors ease some of that stress locally, Creager said, but they don't appear to account for all of it.
"Each one of these slip events puts more stress on the area of the plate boundary where megathrust earthquakes occur, which is shallower and farther to the west, bringing you closer to the next big event," he said. "There's nothing to tell you which one will be the trigger."
Since the slip events and intervening small tremors don't accommodate all of the stress built up on the fault, scientists are getting a better idea of just what the hazard from a megathrust earthquake is in the Seattle area. One benefit from that is the ability to revise building codes so structures will be better able to withstand the immense shaking from a great quake, particularly if the source is substantially closer to the city than it was previously expected to be.
"We'd like to go back and see how much slip has occurred in these slip events, compared to how much should have occurred," Creager said. "Then we'll know how much of that slip will have to be accommodated in a megathrust earthquake, or through other processes."
2009 AGU Fall Meeting, San Francisco 14 - 18 December
Link to AGU Meeting
Celebrex undermines aspirin
University of Michigan Health System News Room (December 14, 2009)
Painkiller Undermines Aspirin's Anti-Clotting Action
Millions of Americans take Celebrex for arthritis or other pain. Many, if they are middle-aged or older, also take a low-dose aspirin tablet daily to reduce the risk of heart attack and stroke. Yet they may be getting little protection, because Celebrex keeps the aspirin from doing its job effectively, a new study suggests.
In laboratory studies, University of Michigan researchers found that several coxibs, the drug class to which Celebrex belongs, interfere with aspirin's ability to discourage blood clots, if the aspirin is taken in low doses. Celebrex, also known as celecoxib, is the only coxib currently on the market.
Reference:
Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1.
Gilad Rimon, Ranjinder S. Sidhu, D. Adam Lauver, Jullia Y. Lee, Narayan P. Sharma, Chong Yuan, Ryan A. Frieler, Raymond C. Trievel, Benedict R. Lucchesi and William L. Smith
Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0909765106
Link to PNAS abstract
‘Sexual risk behaviors’
Roger Pebody for Aidsmap (December 17, 2009)
Half of new diagnoses in French gay men are recent infections
Over the last five years, half of the gay men diagnosed with HIV in France acquired their infection in the six months before diagnosis, researchers report in the 3 December issue of Eurosurveillance. This suggests that HIV incidence (the rate of new infections) is extremely high in this population. However it may also point to high rates of testing among some groups of gay men.
After many years in which only AIDS diagnoses had to be reported, the French public health reporting system has been considerably strengthened in recent years. Since 2003, reporting of HIV diagnosis has been mandatory. Moreover, a test to identify recent infections is routinely recommended, as long as the individual gives consent.
The test for recent infection is one of a number of techniques sometimes referred to as STARHS or incidence tests which look for specific antibody markers that give different results in the months following infection. If a test gives a result below a pre-determined cut-off point, it is deemed to be a recent infection.
Each year, around 6,500 - 7,500 people are newly diagnosed with HIV in France. The numbers of gay men (and other men who have sex with men) diagnosed has increased from below 2,000 in 2003 to around 2,500 for each of the last three years.
Epidemiologists analyzed the available data on gay men diagnosed between 2003 and 2008, although quite a lot of information is missing. Clinicians had failed to supply information on mode of transmission for 31% of individuals who were diagnosed, and recent infection results were only available for 4,819 gay men.
The average age for gay men diagnosed was 37. Independently of the test for recent infection results, 19% of diagnosed gay men were thought by their clinician to be diagnosed during primary infection.
Moreover, the test for recent infection showed that 48% of men had been infected in the previous six months. This figure remained stable between 2003 and 2008.
Men who had taken at least three HIV tests in their life were four times more likely to be diagnosed with recent infection than men who were diagnosed on their first HIV test. Being diagnosed in recent infection was more common both for men with French nationality and those with higher socio-economic status.
Moreover, recent infection was more common for younger men, with 57% of those diagnosed aged 15-29 having recent infection, compared to 30% of men aged 50 and over. In line with this, whereas 11% of all gay men were diagnosed very late (with an AIDS-defining illness) this figure rose to 27% for those men aged over 50. The numbers of men diagnosed late declined during the study period.
Older men were more likely to take a test because of symptoms, whereas younger men tended to do because of their risk behavior.
The authors note that the high number of recent infections in gay men probably reflects both testing behavior and HIV incidence. They plan to publish a study estimating incidence rates in 2010.
Describing their data as worrying, they comment: “Prevention campaigns remain crucial, but they do not seem sufficient to contain sexual risk behaviors among MSM in France, despite the wide availability of screening, condoms and information and the fact that MSM represent a highly educated sub-population”.
In the United Kingdom, the Health Protection Agency (HPA) is also rolling out the use of recent infection tests. Whereas a 2007 study from Brighton estimated that half of new diagnoses in gay men were recent infections, the HPA’s preliminary results for 2009 suggest much lower figures - one-in-five for gay men, and one-in-ten for heterosexuals.
Reference
Recently acquired HIV infection in men who have sex with men (MSM) in France, 2003-2008
Caroline Semaille, F Cazein, F Lot, J Pillonel, S Le Vu, Y Le Strat, V Bousquet, A Velter, F Barin
Eurosurveillance, Volume 14, Issue 48, 03 December 2009
Link to Eurosurveillance article
MRSA costs as much as $60,000 per patient
Duke Medicine News and Communications (December 15, 2009)
MRSA Leads to Worse Outcomes, Staggering Expenses for Surgical Patients
Post-surgical infections significantly increase the chance of hospital readmission and death and cost as much as $60,000 per patient, according to Duke University Medical Center researchers who conducted the largest study of its kind to date.
"We conducted a multi-center study of multiple surgical procedure types among 659 patients to determine clinical and financial outcomes of surgical site infections that are directly attributable to MRSA (methicillin-resistant Stapylococcus aureus)," said Deverick J. Anderson, M.D., MPH, an infectious diseases specialist at Duke University Medical Center and lead author of the study. "We found the impact of methicillin-resistance on surgical patients is substantial and that preventing a single case of surgical site infection due to MRSA can potentially save hospitals as much as $60,000."
Previously published research on surgical site infections provided conflicting conclusions. For the Duke study, researchers looked at the 90-day postoperative period for patients over a five-year period in one tertiary care center and six community hospitals in the Duke Infection Control Outreach Network (DICON). Created in 1997, DICON assists community hospitals in improving quality of care and enhancing patient safety, while minimizing the costs associated with non-evidence based approaches to infection control.
The researchers compared hospital readmission, mortality, length of hospital stay and hospital charges for patients in three groups. Some had surgical site infections due to MRSA, some were infected with methicillin-susceptible Staphylococcus aureus (MSSA), and some were uninfected. The study evaluated deep-incision and organ/space infections, which are more severe than superficial infections at the site of incision.
"We found that patients with surgical site infections due to MRSA were 35 times more likely to be readmitted and seven times more likely to die within 90 days compared to uninfected surgical patients," Anderson said. "These patients also required more than three weeks of additional hospitalization and accrued more than $60,000 in additional charges."
The researchers found most of the outcomes for MRSA compared to MSSA were worse, as anticipated, however one finding was surprising, according to Anderson. "Our findings show that methicillin-resistance contributed to longer hospital stays and increased hospital charges but did not increase the risk of mortality," he said.
The data shows that patients with surgical site infections due to MRSA compared to MSSA on average required six more days of hospitalization and incurred $24,000 in additional charges.
"For the seven hospitals we looked at, the total estimated cost resulting from surgical site infections due to MRSA was more than $19 million," Anderson said. "That's a staggering amount, which demonstrates an area of cost-saving potential for these institutions and other community hospitals."
The Duke study provides the first cost impact data tied to post-surgical MRSA infection in a large group of hospitals. "Given our estimated cost of one MRSA case, we can conclude that a $60,000 intervention to prevent even one of these infections would be cost-effective for an institution," Anderson said. "With this new financial data, greater emphasis should be placed on an effort to design and evaluate specific preventative interventions."
reference
Clinical and Financial Outcomes Due to Methicillin Resistant Staphylococcus aureus Surgical Site Infection: A Multi-Center Matched Outcomes Study
Deverick J. Anderson, Keith S. Kaye, Luke F. Chen, Kenneth E. Schmader, Yong Choi, Richard Sloane, Daniel J. Sexton,
PLoS ONE 4(12): e8305. doi:10.1371/journal.pone.0008305
Link to PLoS ONE article
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