Bench Press

Two weeks ago a large wildfire broke out north of Los Angeles within the Angeles National Forest. It grew quickly becoming the largest wildfire in Los Angeles County’s history. A suspected case of arson, it has burned over 160,000 acres as of today and is only 62 percent contained. The immediate impact of the Station Fire is illustrated dramatically by this image produced by NASA’s Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument on the Terra satellite.

Even having lived in San Diego during the 2007 wildfires, images like that one are just incredible. In addition to this image NASA’s Aqua satellite monitored carbon monoxide concentration within the atmosphere over the first seven days of the fire. Click through for the full animation.Thanks to NASA’s satellites some potentially useful scientific data can be gleaned from this disaster. Too bad they don’t have a satellite to help us catch those responsible.

(Station Fire Image)(Carbon monoxide measurements)

As Ben mentioned on Monday, we at Bench Press were disappointed that we were unable to attend the 2009 Science Online London Conference, but we were glad to see the amazing coverage within the blogosphere. One of the panels I was interested in was the first breakout session titled “What is a scientific paper?”. A discussion on the essence of scientific papers could be incredibly enlightening about steps needed to modernize scientific communication and publishing.

Having read through various notes and posts about the panel I have to agree with Cameron Neylon that while the panel’s discussion on methods to modernize papers themselves had some interesting ideas, a key issue with papers was glossed over; their continued publication in antiquated vessels known as journals. As Cameron Neylon writes:

The journal used to play an important role in publication. The publisher still has an important role but we need to step outside the notion of the journal and present different types of content and objects in the best way for that set of objects. The journal as brand may still have a role to play although I think that is increasingly going to be important only at the very top of the market. The idea of the journal is both constraining our thinking about how best to publish different types of research object and distorting the way we do and communicate science. Data publication should be optimized for access to and discoverability of data, software publication should make the software available and useable. Neither are particularly helped by putting “papers” in “journals”. They are helped by creating stable, appropriate publication mechanisms, with appropriate review mechanisms, making them citeable and making them valued. The point at which our response to needing to publish things stops being “well we’d better create a journal for that” then we might just have made it into the 21st century.

Cameron argues effectively that the journal, as used today, does little if anything to optimize access and discovery of data thereby constraining scientific communication and handicapping scientific progress.

While the panel may not have addressed this key issue thoroughly enough, I was happy to see that PLoS has taken a first step to address the limitations of the traditional journal with their new project PLoS Currents: Influenza. As described in their FAQ PLoS Currents: Influenza is

a website for immediate, open communication and discussion of new scientific data, analyses, and ideas in a critical research area. Submissions are screened by a group of leading researchers in the field, and those deemed appropriate are posted immediately and publicly archived at the National Center for Biotechnology Information (NCBI). All content is open access, available under the terms of the Creative Commons Attribution License.

The explicit goal of this project is to provide easy and efficient access to data on Influenza, in hopes that scientific discussion and breakthroughs can be made in a more timely manner. While PLoS still differentiates Currents from Journals, their step out of the typical scientific publishing space with this project is commendable and looks like a great first step at expanding scientific publication. Hopefully this experiment works out and other publishers will begin to experiment as well.

For more coverage on PLoS Currents: Influenza, Bora Zivkovic has a great introductory post.

Previously, Ben wrote a post about innovative use of the virtual world Second Life for simulating N-body problems. One of the groups behind the impressive OpenSim mod, the Meta Institute of Computational Astrophysics (MICA), is incredibly unique in that the organization itself is an exploration into the utility of emerging virtual world (VW) technologies (e.g. SecondLife) for scientific and academic work.

A group of scientists from the California Institute of Technology, Princeton, Drexel University, and the Massachusetts Institute of Technology founded MICA in the spring of 2008 in order to explore and take advantage of what they saw as a new frontier in collaboration and information dissemination. MICA’s goals are¹:

• Exploration, development and promotion of VWs and VR technologies for professional research in astronomy and related fields.
• To provide and develop novel social networking venues and mechanisms for scientific collaboration and communications, including professional meetings, effective telepresence, etc.
• Use of VWs and VR technologies for education and public outreach.
• To act as a forum for exchange of ideas and joint efforts with other scientific disciplines in promoting these goals for science and scholarship in general.

In addition to the collaborative research we’ve written about before MICA also “conducts weekly professional seminars, bi-weekly popular lectures, and many other regularly scheduled and occasional professional discussions and public outreach events, all of them in [SecondLife].” A screenshot of one of their astrophysics seminars can been seen below. MICA has also begun experimenting with various teaching formats for undergraduate and graduate level courses.

MICA members attending a weekly astrophysics seminar by Dr. M. Trenti, given in the StellaNova sim in SecondLife.

What really impresses me about MICA however is their belief in the platform.

[W]e wish to lead by example, and demonstrate the utility of VWs and immersive VR environments generally for scientific research in fields other than humanities and social sciences (where we believe the case is already strong). In that process, we hope to define the “best practices” and optimal use of VR tools in research and education, including scholarly communications. This is the kind of activity that we expect will engage a much broader segment of the academic community in exploration and use of VR technologies. Second, we hope to develop new research tools and techniques, and help lay the foundations of the informational environments for the next generation of VR-enabled Web.

Hopefully MICA’s innovative use of SecondLife will prompt other scientists to follow. I definitely want to check out one of the lectures one of these days.

(Exploring Use of Virtual Worlds as a Scientific Research Platform: The Meta-Institute for Computational Astrophysics)

As technology continues to advance the ubiquitous nature of certain devices prompts innovative people to come up with amazing new uses for everyday items. A perfect example of this is the cell phone. We’ve already shown you smartphones that can take and record ultrasound images as well as a nifty Android application that makes stargazing easy for the amateur astronomer in all of us. Now a team led by Dr. Daniel Fletcher at UC Berkeley in collaboration with researchers at UCSF have turned the smartphone into an incredibly effective microscopy device.

Light microscopy is a vital tool for the diagnosis and screening of various diseases. Unfortunately in many regions of the world access is limited due to availability or lack of portability. Dr. Fletcher’s group looked to solve this problem by taking off the shelf components and building a solution that would be cheap and effective. Fletcher’s group built a mobile-phone mounted light microscope, dubbed the CellScope, capable of providing images detailed enough to help diagnose diseases like malaria and tuberculosis. Using a mobile phone as the platform for the microscope also allows images to be saved and transmitted to clinical experts for further analysis.

The CellScope was put through it’s paces by Dr. Fletcher’s team as they tested it in various applications. As seen in the figure below sickle shaped red blood cells are clearly visible within the image of a blood smear sample allowing the diagnosis of malaria.

In addition to taking diagnostically clear images of blood smears, Dr. Fletcher’s group tested the CellScope with fluorescent filters to see if the CellScope could be utilized in an increasingly popular tuberculosis screening and monitoring assay.

As seen above the fluorescent staining of tuberculosis bacilli in spittum is remarkably clear for a microscope attachment on a mobile phone. In the C panel of the above figure, Dr. Fletcher’s group also attempted to harness the computational power of the mobile phone by developing software to automatically count and process the fluorescent image.

The CellScope’s effectiveness, portability, and low cost make it an incredible tool for health care providers throughout the world. More details available at PLoS ONE.

(PLoS ONE: Mobile Phone Based Clinical Microscopy for Global Health Applications)

In 2003 an unknown virus suddenly emerged in Guangdong China and proceeded to spread rapidly around the world. The SARS coronavirus disseminated around the world via the global air transportation network with stunning efficiency, highlighting one of the unintended consequences of the globe’s vast airline system. After the SARS outbreak, a group at St. Michael’s Hospital in Toronto, took it upon themselves to study the SARS outbreak in detail. The end goal to develop effective strategies to deal with future epidemics. Their project dubbed Bio.Diaspora took a multidisciplinary approach in analyzing air traffic patterns and the distribution of infectious diseases. Their self proclaimed mission:

Understand global patterns of human travel via commercial airlines as a way to predict how emerging infectious diseases are most likely to spread around the world – and consequently apply this knowledge to help the world’s cities and countries better prepare for and respond to global infectious disease threats of tomorrow.

The Bio.Diaspora team believed that not only more applied research into the impacts of global population mobility on public health and security is necessary, but access to quality data on global air transportation and traffic patterns is needed as well. They sought to fulfill this need by:

[D]eveloping a data warehouse for the sole purpose of conducting methodological and applied research on commercial air travel and emerging infectious disease threats. This report embodies rigorous analysis of these data from multiple scientific perspectives – medicine, infectious diseases, public health, health policy, biostatistics, geographic sciences, network analysis, computer sciences, and mathematical modeling.

Their thorough analysis accounted for numerous factors and yielded a report just prior to the emergence of the H1N1 influenza (Swine Flu) pandemic. One of the really interesting parts of the Bio.Diaspora report was the numerous simulations done on potential H5N1 avian influenza transmission from emergence in numerous potential cities around the world.

Click through for interactive version.

The above graphic illustrates the likelihood of importation of H5N1 avian influenza into various areas of the world with an epidemic beginning in São Paulo, Brazil. This caught my eye as it seemingly foreshadowed the H1N1 epidemic. After the emergence of H1N1, the Bio.Diaspora team went back to study the air traffic patterns of the initial stages of the spread (March and April 2009) from Mexico. Running simulations like those from the Bio.Diaspora project’s report they were able to produce predictions based on the flight itineraries (data shown below) that correlated highly with the observed transmission pattern. Their complete analysis is published in the New England Journal of Medicine.

Destination Cities and Corresponding Volumes of International Passengers Arriving from Mexico between March 1 and April 30, 2008.

The Bio.Diaspora project team’s work on both the SARS epidemic and now the H1N1 pandemic illustrate that there’s still much to learn about managing public health crises on a global scale thanks to the highly interconnected nature of today’s cities. It’s a much smaller world now and new tools and ideas will be necessary to deal with future emerging diseases.

(Bio.Diaspora)(Spread of a Novel Influenza A (H1N1) Virus via Global Airline Transportation)

A few weeks ago I wrote a post about the development of the Standoff Patient Triage Tool, an impressive use of lasers in order to make health critical readings of patients from a distance. Well one of the best things about science is that many people can utilize the same tools to come up with unique methods and solutions for any given problem. In this case, researchers have used lasers to develop a technology that could someday revolutionize imaging procedures in medicine.

Photoacoustic imaging of melanoma in vivo.

Photoacoustic tomography is the basis behind a new imaging technology being developed in hopes of providing more flexible and cost effective devices for physicians. The technique takes advantage of ultrasonic emissions produced when a non-ionizing laser pulse is directed towards a tissue. The emissions, resulting from transient thermoelastic expansion of the target tissue due to absorption of the laser energy, are detected and analyzed with various algorithms to construct an image (2D or 3D) of the targeted area. This differs from the reliance on the doppler shift produced by the reflected laser beam in the SPTT.

Images of vasculature like the one seen on the right can be produced by using photoacoustic tomography without the injection of contrast as differences between the molecular composition of the target can be used instead. In the example to the right, the difference between oxygenated and deoxygenated blood is an effective natural contrast. Photoacoustic tomography also presents other benefits over traditional imaging techniques as explained by The Economist:

CT scans also involve potentially harmful ionising radiation. And MRI and CT scans are very expensive, using machines that cost millions of dollars and require dedicated staff to operate them. Photoacoustic tomography, by contrast, could eventually be performed using portable hand-held devices, similar to those used for ultrasound scanning. This would allow doctors to diagnose and monitor patients in clinics, and reduce the need to refer them to consultants.

The adaptability of this nascent technology is also impressive as researchers are already looking at using it to detect specific ailments such as brain lesions and cancer. In the case of cancer, the ability to accurately image vasculature could allow doctors to monitor patients for the development of new blood vessels (angiogenesis) a hallmark of cancer development.

While there are some issues to work out with this new technique, such as the lack of imaging depth (ultrasound signal emitted is reduced the deeper the tissue lies) and ultrasound distortion from varying tissue types within the human body (e.g. bone vs muscle), photoacoustic imaging is a very promising new technology.

(Source)

Like my fellow Bench Press blogger Ben, I’m a fairly avid Star Trek fan. Having spent many hours during my formative years watching syndicated episodes I always wondered if we’d ever have some of the amazing devices in the show. One of the devices that captured my imagination was the Tricorder (pictured right). It amazed me that such a tiny device could provide so much utility throughout the show. The Tricorder’s versatility allowed it to do pretty much anything in the show, but what I always remembered was it’s medical utility. It allowed characters like “the Doctor” to analyze any number of ailments quickly and accurately.

While we don’t have the technology to make a Tricorder as effective as the ones used in Star Trek, the U.S. Department of Homeland Security’s Science and Technology Directorate (S&T) is developing a tool called the Standoff Patient Triage Tool (SPTT). The purpose of the SPTT is to aid first responders at a disaster triage patients quickly and accurately. Triaging patients with traditional methods can take 3-5 minutes per person. This can become an extremely difficult and time intensive task during a disaster, exactly the opposite of what we’d like. Therefore, the goal of the SPTT is to reduce triage time to 30 seconds per patient by providing accurate readings of pulse, body temperature, and respiration from up to twenty paces away all in a portable package about the size of a legal notebook.

A drawing of the proposed 15 inch by 8.5 inch x 6 inch Standoff Patient Triage Tool (SPTT) with the following features. 1) 4 x 6 display window; 2) Control button; 3) Infrared camera window; 4) Visible camera window; 5) Ranging subassembly window; 6) Shock bumpers. (Source: DHS S&T)

The SPTT takes advantage of Laser Doppler Vibrometry (LDV) in conjunction with a visual and infrared camera to make it’s readings. LDV takes advantage of the doppler shift produced when a laser bounces off a moving target. The shift in frequency upon return of the laser beam is measured and then analyzed in order to determine the velocity over time of the target. In this case, the SPTT’s vibrometer detects the movement of blood vessels and utilizes algorithms to extrapolate relevant data. So far researchers have found that the SPTT can produce strong readings from the head, chest, abdomen and foot. Currently, taking readings from the cartoid artery region of the neck appears to be the best option. Further testing needs to be done on patients in awkward positions, as well as with differing layers of clothing.

While the SPTT can’t do everything a tricorder can do, it appears to be taking a great first step in providing a portable device capable of providing first responders with accurate job critical data that will help them save lives. Maybe it’s only a matter of time before doctors start waving a small device around the patients while asking them what brings them into the office that day.

(Image Source)(DHS S&T Press Release)

During the past month’s global swine flu emergency providing health care professionals around the world with accurate information was critical to understanding and potentially containing the outbreak. The time sensitive nature of dealing with an emerging disease highlighted the importance of developing an effective communication channel that is quick, accurate, and accessible by numerous individuals. Traditional paper distribution channels, mailing notifications to primary care physicians, can delay the receipt of time sensitive materials by 72-96 hours. Thus, the question becomes how do you design a system that can be accessed quickly and easily by a maximum number of health care professionals, while still providing quality information.

A new web application developed by the Indiana Health Information Exchange (IHIE) interfacing with a service called Docs4Docs®, provided by the Regenstrief Institute, appears to have answered that question. The IHIE’s web portal allows electronic communication of public health messages to any registered health care provider. Registered users can also send messages back through the portal to be disseminated across the network. The web portal’s simplicity allows it to bridge the gap between paper-based and electronic-based medical offices thereby ensuring that even doctors in rural areas without advanced IT infrastructure can receive and contribute critical information.

Docs4Docs® also leverages the Indiana Network for Patient Care (INPC) which is a secure community health records system, providing patient data whenever needed. Dr. Shaun Grannis, a Regenstrief researcher, explains “[b]y working with our public health partners to seamlessly deliver public health alerts in precisely the same manner that physicians receive time-sensitive clinical information for patient care, we ensure that physicians have the right information at the time they need to see it”. This was exemplified by the first electronic health alert sent out across the Docs4Docs® network with regards to the emerging H1N1 crisis on April 29, 2009.

Last year Regenstrief scientists received a $10 million, 5 year contract from the Centers for Disease Control in order to continue working on developing electronic records and notification systems like those that make up the backbone of the Docs4Docs® service in Indiana. I for one believe that money is going to good use and look forward to seeing other states follow Indiana’s lead with regards to developing new electronic records and notification systems.

In order to deal with the global outbreak of swine flu effectively, tracking the number of swine flu cases is imperative. Having as much accurate data as possible regarding the epidemic is essential for evaluating what moves the global community ought to start taking to make it through this outbreak. Thus, using quick and accurate tools to evaluate the countless samples  being collected around the world is an absolute necessity. Luckily scientists at the University of Colorado and InDevR, a small biotech in Colorado, may have exactly what the world needs in a microarray chip dubbed the FluChip.

In 2005 Dr. Kathy Rowlen, CEO of InDevR, led a team at the University of Colorado working with the Centers for Disease Control and Prevention (CDC) in developing the FluChip in order to allow labs across the world to quickly distinguish samples between 72 different influenza strains. Her group’s work produced a viable testing platform that produced results in less than 12 hours with impressive accuracy.

Now Dr. Kathy Rowlen and InDevR have licensed the FluChip technology from the University of Colorado. InDevR has arranged to begin testing samples of the swine flu on a M-gene variant of the FluChip while also working on improving the initial design by incorporating new technologies, hopefully making a new assay basic enough that any lab with PCR capabilities will be able to utilize it. Here’s to hoping the FluChip will help us get a better picture of the current state of the swine flu epidemic.

InDevR Press Release:

InDevR, a small biotech company in Boulder, CO, announced today that they have licensed the FluChip technology from the University of Colorado.  The FluChip was invented by a joint team of scientists at the University of Colorado and the Centers for Disease Control and Prevention in an NIH sponsored effort led by Professor Kathy Rowlen.  Rowlen, now the CEO of InDevR, said that InDevR has arranged to test genetic material from the recent swine H1N1 virus on the MChip as well as other versions of the FluChip which are under development.  According to Rowlen “Based on work we conducted a couple of years ago, it appears that the M-gene version of the FluChip will be able to distinguish human H1N1 viruses from the new swine H1N1 virus.  If that proves to be the case, the FluChip will be a much needed and powerful new tool for surveillance since all of the current influenza diagnostics on the market are unable to subtype this virus.” The most popular diagnostic tests for influenza include rapid immunoassays, which are only able to identify the type (A or B) of influenza virus, and reverse-transcriptase polymerase chain reaction assays, which were designed for human-adapted influenza viruses and are not able to identify the swine H1N1 subtype.  State Public Health Laboratories must now send any influenza A viruses that cannot be subtyped using existing diagnostics to the CDC for analysis by genome sequencing or viral isolation.  The CDC must select viruses to analyze since it is not possible to run every sample collected from a large number of Public Health Labs.

The M-gene based FluChip has been demonstrated to delineate human-adapted viruses from non-human viruses, such as the H1N1 virus that caused the 1918 “Spanish Flu”.  “Since the FluChip assay can be conducted within a single day it could be employed in State Public Health Laboratories to greatly enhance influenza surveillance and our ability to track the virus,” Rowlen said.  InDevR will combine the FluChip technology with an innovative detection technology (NESATM), which InDevR also licensed from the University of Colorado and further developed with NIH sponsorship, to make the FluChip assay inexpensive and easy to use in any lab that has basic PCR capabilities.  “Kathy and her team have been engaged with this and similar diagnostic technology for many years,” said Mary Tapolsky, Senior Licensing Manager at the University of Colorado Technology Transfer Office. “CU TTO is excited about this experienced and motivated group developing and commercializing this promising technology.

As genomes have been sequenced over the past few decades scientists have looked for new ways to analyze and interpret the wealth of information. They’ve developed numerous algorithms with goals ranging from organizing evolutionary family trees (inspired by plagiarism detecting software) to aligning genetic sequences. All of this to answer the numerous questions that can now be asked thanks to sequence databases. One of the many things scientists have attempted to study is positive selection in protein-coding genes.

Positive selection of advantageous gene mutation is particularly interesting to scientists as it can provide insight into the function of new genes. However, positive selection is difficult to detect and analyze as neutral and deleterious mutations predominate advantageous mutations in frequency. Initially scientists looked for positive selection by simply comparing the ratio (/omega) of nonsynonymous nucleotide substitutions (d_N) to the number of synonymous nucleotide substitutions (d_S) between homologous protein-coding gene sequences while utilizing Fisher exact tests to accept or reject a null hypothesis of neutral selection¹.

Over the years scientists developed additional statistical analyses to infer positive selection. Two of the most popular methods are the branch-site method (BSM) and site-specific method. The BSM utilizes a likelihood ratio test to detect positive selection within a given phylogenic branch. The site-specific method on the other hand utilizes /omega to look for specific amino acid substitutions that are positively selected. Both of these methods have been utilized in hundreds of papers and seemingly provided a great deal of insight into potential points of positive selection within various genomes. What would you say then when told that both of these methods contain significant flaws which provide an inordinate number of false positives?

Bovine Rhodopsin protein with predicted sites in red and experimentally determined in blue. (Adapted from Yokoyama et al. 2008 PNAS)

That’s exactly what Masatoshi Nei and his group believe to have shown in a recent paper evaluating the reliability of the branch-site and site-specific methods. Nei’s group utilized several controlled computer simulations as well as data collected by Shozo Yokoyama, at Emory University, on dim-light vision opsins in vertebrates² in their studies determining that both the branch-site and site-specific methods yielded far too many false positives. Nei and his group contend:

This low rate of predictability occurs because most of the current statistical methods are designed to identify codon sites with high /omega values, which may not have anything to do with functional changes. The codon sites showing functional changes generally do not show a high /omega value. To understand adaptive evolution, some form of experimental confirmation is necessary.

From this paper it looks like scientists looking for high /omega values may have been chasing ghosts by assuming that amino acid changes result in functional changes indicating proof of positive selection. The potential impact this will have on hundreds of papers is stunning. In the end the take home message is that statistical analyses, no matter how elegant, have their limits and ought to be utilized in conjunction with experimental data as much as possible.

(Sources: 1 – Reliabilities of identifying positive selection by the branch-site and the site-prediction methods , 2 – Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebrates )

updated: Had to change all the &omega to /omega because WordPress kept changing it into ? for some reason…bah