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They might not be as pretty as their much larger counterparts, but unlike a sparkling diamond ring, the tiny 1) ___ known as nanodiamonds, might actually end up doing some good in the world. Scientists at Northwestern University have demonstrated that these relatively new nanomaterials can shuttle 2) ___ drugs to cells without producing the negative effects of today’s delivery agents. Clusters of the nanodiamonds surrounding the drugs block them off from 3) ___ cells, preventing unnecessary damage, and then release them upon reaching the intended targets. Just as important, the leftover diamonds, hundreds of thousands of which could cram onto the eye of a 4) ___, don’t induce inflammation in cells once they’ve done their job. The study, the first to demonstrate the usefulness of the material in 5) ___, is published online in Nano Letters.

ANSWERS: 1) particles; 2) chemotherapy; 3) healthy; 4) needle; 5) biomedicine

Target Health Inc. is pleased to announce the publication of a new article entitled, “The Paperless Trial – Past, Present and Future” which can be found in the Autumn edition of The European Pharmaceutical Contractor. The article deals with the integration of electronic data capture (EDC) in clinical trials and the electronic health record (EHR). The article is co-authored with Imogene Grimes, Douglas Nadler and Vadim Vadim Tantsyura of Regeneron Pharmaceuticals, Linda Harnevo of Global Medical Networks Israel Ltd, and Yossef Bahagon at the Department of Family Medicine, Clalit Health Services, Hebrew University Hadassah Medical School.

vadim.jpg Vadim Tantsyura has 15 years of extensive engineering, IT and data management experience, spanning all aspects of clinical data management. Vadim is currently Head of Data Management at Regeneron Pharmaceuticals in Tarrytown, NY. Vadim holds a BS in Electrical Engineering from Kiev Higher Military School of Air Force (Ukraine), an MS in Computer Engineering from Kiev State University, a BS in Finance from Southern Connecticut State University and an MA in Economics from Yale University.
linda.jpg Dr Linda E Harnevo is the inventor of the Global Medical Networks (GMN) concept and technology, and is presently responsible for the management and guidance of the Global company and new business development. Linda is an avid entrepreneur, with renowned expertise in medical visualisation technology, both in Israel and abroad. Linda sits on the Board of Directors of several prominent public companies in the US, and holds a PhD from the Weitzman Institute in Applied Mathematics.
yossef.jpg Dr Yossef Bahagon is a primary care and family physician with expertise in evidence-based medicine and clinical informatics. He currently serves as Chief Medical Informatics Officer at the Planning and Health Policy Division of Clalit Health Services. Yossef has also served as the Medical Director of the Israeli Clinical Information Center. He holds an MD degree from the Hebrew University Hadassah Medical School.
jules.jpg Dr Jules T Mitchel, President and Co-Founder of Target Health Inc, brings over 25 years’ experience, both in the pharmaceutical industry and in basic research. Jules has held industry positions at Ayerst Laboratories (now Wyeth, Inc), Pfizer Laboratories and Pfizer Consumer Health Care, and academic positions at New York Medical College, Cornell University School of Medicine and NYU School of Medicine. Jules is a member of the American Society of Clinical Pharmacology and Therapeutics where he is Section Head for Dermatology.
andrew.jpg Andrew Moncrieffe is the Director of Technology Development at Target Health Inc. His responsibilities include software architecture, development methodology and software implementation. Andrew has over 20 years’ experience in software development. He is also a Lecturer in the Department of Information Technology at New York University.
imogene.jpg Imogene Grimes is Vice President, Statistics, Data Management and Informatics at Regeneron Pharmaceuticals, Inc. She has a PhD in Biostatistics from the University of North Carolina and 24 years’ experience in the pharmaceutical industry, including a decade at major pharmaceutical companies (Glaxo and Pfizer) and a decade in a CRO. Imogen has managed clinical monitoring, report writing, CRF development, pharmacokinetics and regulatory affairs.
doug.jpg Douglas Nadler is an Associate Director of Statistical Services at Regeneron Pharmaceuticals. He has been in the pharmaceutical/biotech industry for nine years. He is currently working on a BLA submission for the IL 1 Trap CAPS (FCAS) submission, as well as analysing VEGF Trap ophthalmology results. He has a Masters in Statistics (Stony Brook) as well as an MBA in MIS (Iona).

Electronic data capture (EDC) and the electronic health record (EHR) are radically changing the ways the pharmaceutical industry manages clinical research data and physicians manage their patients. EDC allows the users at clinical research sites to enter, review and analyse data in real-time, whereas the EHR allows users at a clinic or hospital to do the same. While these two functions are very similar in both structure and function, adoption of these systems is still relatively slow, especially in the US (1,2). From the clinical research perspective, there is no functional integration of EHR and EDC (3). One result is that, whether the clinical trial is being performed using EDC or a paper case report form (CRF), there is a loss of efficiency when a study site has an EHR. While adoption of the EHR and EDC is still lagging behind, there is no question that EDC and the EHR are here to stay. When properly designed, EHR and EDC solutions offer a convenient, cost-effective approach for the clinical sites to enter data, manage data and generate reports.

In the pharmaceutical industry today, EDC offers clinical research associates (CRAs) the ability to review data prior to visiting the study site, monitor the data electronically onsite and resolve queries electronically. EDC also allows data managers to assure data quality more effectively by having online data validation checks. Project managers are also able to evaluate the study status in realtime. Back in 1997, Kelly and Oldham discussed the challenges for the implementation of an Internet-based clinical trial, as well as the obvious advantages of its use in drug development (4). Chadwick and Gisanti (5) gave a vision into the future and Garvey (6) addressed EDC as state-of-the-art technology. Several publications by Mitchel et al (1,7,9,10) documented many of the advantages of EDC over paper CRF-based studies.

PAST, PRESENT AND FUTURE

Historically, data management for a paper CRF-based clinical trial first included verifying the precision and accuracy of the data entered on the paper CRFs against the source documents. This is done at the study sites by the CRAs. Basically, this task evaluated how well the data were transcribed. In addition, the study monitor also made sure that the protocol was being followed and all protocol deviations and violations were identified. Monitors also assured that all regulatory documents were present and consistent with good clinical practice (GCP) requirements. The ‘white’ copies of the paper CRFs were then ‘pulled’ by the study monitor and delivered to data management. The data were ‘double keyed’ and the data entry compared for precision, using a ‘data compare’ program. Once data entry errors were identified and fixed, off-line (batch) edit checks were run for data validation purposes. Data entry items, which were illegible or clearly incorrect, or data errors identified as a result of the batch edit checks, were resolved via the query process, which could be manual or electronic. As a final step, once the queries were resolved, a QC person checked the data listings against the paper CRFs to assure that all of the data in the listings were matching.

Currently, with EDC systems, most sites still use paper source documents. However, instead of transcribing source document data to a paper CRF, the data are transcribed from source documents to the EDC system. Double-key data entry, and all associated tasks, have been eliminated. Interactive edit checks now exist at the time of data entry, which allow the data entry person to assure that any illogical or out-of-range data are actually correct. If not, the entries can be corrected or commented upon at the time of electronic data entry. In EDC systems, there are built in audit trails to track all changes to the database and electronic queries systems to mange query generation and query resolution. Batch edit checks still need to be run because not all queries can or should be run at the time of data entry.

One of the most promising entities within the field of biomedical informatics lies in the incorporation of clinical informatics and bioinformatics. In the not-too-distant future, EDC will be linked with the EHR, so that all information about a patient will be sourced electronically. When a patient is being considered for a clinical trial, his/her EHR will be searched to evaluate inclusion/exclusion criteria. All baseline data already in the EHR will be ‘pushed’ into the EDC system, and all data related to the clinical trial will be entered once and then reside simultaneously in the EHR and EDC systems. This will allow the clinical site to maintain their source information about a patient for audit purposes, but at the same time allow the pharmaceutical company to have real-time access to the data. In our opinion, tools provided to the pharmaceutical companies by the EDC industry will still be used to create the data entry screens, but these screens will be rendered within the EHR to allow for full data integration. This will allow for standardisation across multiple EDC and EHR systems and the elimination of paper source documents.

The integration of the EDC and the EHR will benefit patients, physicians and pharmaceutical companies, by adding value to each sector while, at the same time, preserving the highest ethical standards. A customised virtual personal medical record, which is available anywhere anytime, enables continuity of care record, hence contributing to medical error reduction and to better informed decisions. It may also enhance the cooperation level of patients within clinical trials as it has a direct and evidently positive impact on the quality of medical care. Realtime, anonymous clinical data accessibility will enable the clinical researchers and the pharmaceutical companies to have an outstanding surveillance, audit trail and data analysis capabilities, in the pre- and post-marketing phases.

CHANGING ROLES OF CRAs AND DATA MANAGERS

With the advent of EDC and EHR’s integration, the role of monitoring data within a clinical trial will change dramatically. No longer will there be a need to verify whether data transcription is correct. When data originally entered in the EHR is the only source document, logic and range checks will pick up any potential errors at the time of data entry. Audit trails will be required to identify those who enter and modify data. The reason for any data modification will be required as per 21 CFR Part 11. EDC-based query systems will still be needed to ask questions about the data. Online data management and batch edit checks will play a major role, while traditional monitoring as we know it will disappear. CRAs will become more like data managers and auditors. Utilising user-friendly web-based document management systems will also allow for all protocol-related study documents to be posted and signed online, so that that ‘paper trails’ as we know them will disappear.

DISCUSSION

One of the main advantages of EHR and EDC systems is that those who are familiar with the data (the clinical study site), enter the data directly into ‘intelligent’ systems. There are no judgements of intent and no guesswork. There are no illegible fields and no symbols which require interpretation. In addition, all missing data and out-of-range data are flagged and require explanations at the time of data entry. Either before or during monitoring, data discrepancies can be confirmed. CRAs will assume some audit and data management functions. Sponsors should be aware that training must be adjusted as workloads are redefined.

When the integration of EHR and EDC systems is properly implemented, there will be major efficiencies in the monitoring of clinical trial data and data management processes. When managed properly, significant time- and cost-savings can be made by: eliminating double key data entry; automating the query system; reducing the time the monitor has to spend at the study site and interacting with the site coordinator; and by reducing the time from last-patient-last-visit to database lock. EHR and EDC systems are here to stay. Eventually, all companies will abandon paper CRFs and move into the electronic world. The first step is deciding ‘what’ a company actually wants to achieve in order to capitalise on the advantages of integrating EHR and EDC systems, and how to turn a ‘concept’ into a ‘requirement’. The second major challenge is ‘how’ to do it. This involves system design, employee training and possibly employee redeployment. The third challenge, and one of the most difficult parts of implementing EHR and EDC systems, has nothing to do with the fundamental technology, but rather with making the necessary changes in structure, mind-set and culture within the sponsoring company as well as at the clinical study sites. Choosing the right people to manage and execute the process is key to the success of any programme.

CONCLUSION

The technology is ready and available. What the industry is waiting for are the innovators, trailblazers and ‘risk-takers’ to take the plunge. The pharmaceutical industry has reached a fork in the road. There will be those who will choose to stay where they are in the short term, and there will be those who will embrace the integration of EHR and EDC systems. The concept presented in this article has the potential to be the next revolution in the digital medical research era. It holds fundamental advantages for patients, their physicians and the R&D community, while emphasising the ethical issue of the patient’s informed consent.

When the integration of EHR and EDC systems is managed properly, time is decreased for: database lock, statistical analyses, final study reports, regulatory submissions and, ultimately, market launch. In addition, time is saved, man-hours and costs are reduced, and the process of clinical research, data management, biostatistics and project management are streamlined. However, in order to accomplish this, companies must be willing to take the necessary steps needed to reevaluate their workflow and resource allocations, as they move to implement EHR and EDC integration.

The authors can be contacted at julesmitchel@targethealth.com

References

1. Mitchel J, Jurewicz E, Flynn-Fuchs K et al, The Role of
CRAs in the Development and Implementation of Internet-
Based Clinical Trial Applications: New Career Opportunities,
Monitor, pp17-21, October 2005

2. Simon SR, Kaushal R, Cleary PD et al, Physicians and
Electronic Health Records – A Statewide Survey, Archives
of Internal Medicine 167: pp507-512, 2007

3. Bleicher P, Integrating EHR with EDC: When Two Worlds
Collide, Applied Clinical Trials, 2nd March, 2006

4. Kelly MA and Oldham J, The Internet and Randomised
Controlled Trials, International Journal of Medical
Informatics 47: pp91-99, 1997

5. Chadwick B and Gisanti S, EDC 2001: A (Pharma)
Space Odyssey, Innovations in Pharmaceutical Technology,
pp92-95, 2001

6. Garvey A, EDC; State of the Art, Innovations in
Pharmaceutical Technology, pp116-118, 2005

7. Mitchel J, You J, Lau A et al, Paper Versus Web;
A Tale of Three Trials, Applied Clinical Trials,
pp34-35, August 2000

8. Mitchel J, You J, Kim YJ, Lau A et al, Internet-Based
Clinical Trials – Practical Considerations, Pharmaceutical
Development and Regulations 1: pp29-39, 2003

9. Mitchel J, Ernst C, Cappi S, Beasley W, Lau A, Kim YJ,
and You J, Meeting the Challenges of Internet-based
Clinical Trials, Applied Clinical Trials, June 2004

10. Mitchel J, You J, Lau A et al, Clinical Trial Data
Integrity. Using Internet-Based Remote Data Entry
to Collect Reliable Data, Applied Clinical Trials,
Supplement, pp6-8, March 2003

Neurology – Amnesia & Music
Click here for the video.

As quoted by Chip Kalfaian , director of the life science solutions division of Cranford, NJ-based Paragon Solutions, “Although consolidation is likely, including acquisitions by contract review organizations (CROs), smaller EDC vendors like Target Health (New York, NY) continue to pop up in the market with dynamic EDC tools.”

Life on EDC Street – By Deborah Borfitz (Bio-IT World Oct. 10, 2007)

By Elinor Mills, News.com
Published on ZDNet News: Oct 17, 2007

I know this may sound crazy, but I don’t have a television.
This isn’t a problem, except when I get glimpses of what I might be missing, like when the New York Mets choked and it was all anybody could talk about in the office that day.

I also happened to catch some episodes of Animal Planet’s Meerkat Manor on a public hospital TV recently. I was captivated by the story of matriarch meerkat “Flower” and her tragic death from a cobra bite while saving her pups in the Kalahari desert. I just had to watch the next episode to see which of her daughters would win the power struggle to succeed her. But how could I do that without cable or even a TV?

I went on a search for some of my old–and new–favorite TV shows on the Internet. The one caveat: it had to be free, because this TV dilettante wasn’t paying for anything other than my phone and DSL broadband service.

While I pay about $30 a month for phone and DSL, my neighbors spend anywhere from $70 to $140 for cable and Internet access, depending on the number of channels and level of service. That cost difference, plus the desire to avoid having a boob tube around, means the laptop is the only screen in my home.

I may be odd, but I’m not alone. A whole 2 percent of U.S. households are TV-less, according to Nielsen. (OK, so I’m almost alone). And nearly 16 percent of American households with Internet access watch television broadcasts online, a report released this week by The Conference Board and TNS Media Intelligence found.

Networks and studios are recognizing this trend. While paid downloads make more money for content producers, ad-supported video streaming is growing–it’s expected to bring in $117 million in revenues this year for producers of prime time and daytime TV programming alone, up from $43 million last year, according to Adams Media Research.

My first step to becoming an Internet couch potato was to search for Meerkat Manor online. I found a link at the top of the search engine’s sponsored results section that led to the Discovery Channel site, where I could watch the last four episodes after installing a video player.

The video quality was poor and the transmission was glitchy. It really ruins the timing of jokes when (Jon) Stewart’s mouth is saying one thing and you are hearing something else.

There was a 10-second ad for Oust air freshener that ran before the show started, and then the Meerkats were on, in all their anthropomorphic glory. I could watch them for hours, but unfortunately, a commercial break came. I was subjected to a 30-second ad this time, from the same air freshener company. Time to check e-mail.

As soon as I heard the commercial end I was back to the screen for more Meerkat adventures. The video quality, while it didn’t seem quite as clear as on a TV, was beautiful. And then, before you knew it, the exact same commercial as before came up. This same ad was shown three times during the show. I somehow thought I would be spared the commercials by watching TV on the Internet. I was wrong.

One of the great laments I’ve had about not having a TV the past few years is that I miss my daily dose of humor–The Daily Show With Jon Stewart. So, I quickly found myself on the Comedy Central site, where Stewart’s monologue from the day before started right up in a very small window. There are also sections called “Most Recent Videos” and “Last Week’s Highlights.” I watched Stewart poking fun at the Republican presidential debate and then conducting an awkward interview with Vice President Cheney’s wife, Lynne.

But what if I don’t just want highlights? What if I want to watch the entire show? While watching a show in segments like this might make for more efficient TV viewing, I missed watching the flow of an entire show, where Stewart and his cohorts often make references to things that happened before the commercial break.

In addition to the fact that the site seemed to be showing the same ad for each of the highlights I viewed, I was squinting to see the screen because the video window was so small. The video quality was poor and the transmission was glitchy. It really ruins the timing of jokes when Stewart’s mouth is saying one thing and you’re hearing something else.

Next, I went straight to TV network Web sites. On ABC, I launched the full episode player, which offered a full screen and mini mode. I had heard that tech entrepreneur and Dallas Mavericks owner Mark Cuban was on Dancing with the Stars, so I thought I’d check that show out.

I was very pleased to see that I could click a button to skip the ad that kept repeating (in this case for Garnier Nutritioniste) shortly after it began. But I was disappointed that I was only able to watch a condensed version of the program for the Web audience, in which they only show the results and highlights and not all the dance numbers. I like watching ballroom dancing, so that was a bummer.

But after watching the highlights from Mark Cuban’s performance I felt a little better. The judges were right–he needs work. And doesn’t Jane Seymour look great and dance well, despite the recent death of her mother?

For NBC, there was a link to the video player right on the search engine I used. I was able to choose between full episodes, two-minute replays and Web exclusives. After viewing a short ad in a small window, up came a full-screen showing of The Office, the U.S. version. I’ve got to say, I didn’t think anyone could play the Rick Gervais character well, but Steve Carell did a great job.

Heading over to check out CBS TV shows on the Web, I was underwhelmed. I mean, aren’t people sick of Survivor already? They did have Late Show with David Letterman , but I could only watch segments with highlights, interviews and the monologue. Again, where was the continuity? The notion of a “show” is removed when you watch it in chunks.

Not that it matters to me, but you’ll still need a TV to watch Major League Baseball or National Football League games for free.

I had pretty much exhausted my list of must-see TV, so I went to TVGuide online. The site has a handy search box at the top, as well as sections on tonight’s and this week’s TV, and music videos.

There’s a combination of free and paid programming. For instance, most of the full episodes of Brothers and Sisters were free, but many of the America’s Top Model episodes cost $1.99 to watch. Then, when I started watching one of the free shows, it took a long time to start playing. Free, but sloooow.

So I switched to a juicy-sounding show called Gossip Girl. It started out with a Verizon wireless ad and then a preview, with a voice over that said: “It takes two to tangle, and girls like these don’t go down without a fight.” Oh boy!

Ignoring my better judgment, I took a peak at Beauty and the Geek and again didn’t make it past the intro. Wow! I had forgotten how much crap was on TV. And the constant commercials are annoying.

I decided to go for something more highbrow, the BBC for news, but found that it doesn’t let you watch the programming online.

Next I checked out a local San Francisco news station, KRON 4. There I watched a segment on the city canceling the annual Halloween party in the Castro district. And I watched a feature on an elderly woman whose home was auctioned off to pay off some of a $1.4 million hospital bill. I viewed the footage in a 3×3-inch window. There was no full-screen option.

Pretty much the only sport I’m interested in watching is tennis, so I headed over to ESPN to see if I could see some matches there. Nope. I typed in “tennis matches video” on a Web search engine and saw links to old Women’s Tennis Association matches and a video on Metacafe of Andre Agassi and Roger Federer putzing around.

Not that it matters to me, but you’ll still need a TV to watch Major League Baseball or National Football League games for free.

There were some sites that offer vintage TV programs, such as Like Television Only Better, where I watched part of a grainy black and white 1957 Jonathan Winters TV show in a small window.

Another site was a real find, wwiTV. It had a long list of countries and categories to choose from to watch live TV Webcasts.

I went to a Portuguese TV station from a town called Guimaraes, but every time I tried to open the player the audio echoed. When I closed the player I ended up on the Guimaraes TV Web site where there was no echo, but the accent was hard to understand despite my having lived in Portugal for a year.

I skipped over to the movie section of wwiTV and saw there were at least 25 channels offering films in English. I clicked on one link and was sent to America Free.TV , where I landed in the middle of a 1969 biker movie with Jack Nicholson and Bruce Dern called The Rebel Rousers.

“We don’t need your type of people in this town,” the sheriff tells them as they ride their choppers into the saloon and dance on the bar. As much as I wanted to see what happens to these misunderstood rogues, I couldn’t stand the stop-motion video, which left large blocks of pixels in place of faces. There was no “on demand” aspect to this channel–you have to know when the movie starts to catch it from the beginning.

Other sites worth mentioning include Joost, which lets you watch a wide variety of TV programming over the Internet for free and with a full-screen option, and the open-source company Miro, which offers free Internet TV and a player that plays any video file.

My unscientific conclusion is there’s a mixed bag of TV programming available online. A lot of it is trash and a lot of it’s glitchy, so I’m definitely not worried about becoming an online TV addict.

I also learned that a show about meerkats is probably the best TV on the Internet.

October 18, 2007
Howard Hughes Medical Institute
For sperm to penetrate an egg, they must first compress into a tight ball before springing into action. Researchers have now discovered a protein that can affect how DNA is packaged inside sperm so that they can scrunch up tightly enough to pierce the outer layer of the egg during fertilization.

The new studies in mice show that if this key protein is missing, DNA in sperm cannot be tightly packaged and the sperm will not be able to penetrate the egg. The researchers speculate that deficiencies in the protein may underlie some forms of male infertility.

“A small molecule that enhances the enzyme’s activity could be a useful fertility drug in cases where compromised function of the gene has caused infertility.”
Yi Zhang

The research team, which was led by Howard Hughes Medical Institute investigator Yi Zhang, published its findings online in Nature on October 18, 2007. Zhang and colleagues at the University of North Carolina at Chapel Hill collaborated on the studies with researchers in the Laboratory of Reproductive and Developmental Toxicology at the National Institutes of Health.

In their experiments, Zhang and his colleagues explored the function of the enzyme Jhdm2a, which is a histone demethylase. Histone demethylase enzymes activate genes by snipping molecules called methyl groups from histones. Histone proteins make up the “smart stuffing” in chromosomes—the core of proteins around which DNA winds so that it is packaged compactly.

Chemical modification of histones — such as the addition or subtraction of methyl groups – is an important mechanism for controlling the activation or repression of genes. This kind of epigenetic control mechanism is separate from other mechanisms that control gene expression, such as regulatory DNA elements that are embedded in the sequences of the genes themselves. Zhang’s research group is one of the leaders in establishing the role of demethylases in regulating gene activity.

The researchers focused on the function of Jhdm2a because their earlier studies had indicated that the gene for the protein is highly active in the testis. The protein also interested Zhang and his colleagues because Jhdm2a protein levels are highest during sperm maturation.

When the researchers knocked out the Jhdm2a gene in mice, they found that the animals’ sperm did not mature properly. On closer examination, they found that the genetic material, called chromatin, in the immature sperm of the knockout mice did not condense normally. Sperm chromatin must condense into a compact form in order for fertilization to be successful.

“In order for sperm to be able to enter the egg, the sperm chromatin has to be tightly packaged,” said Zhang. “It must become like a dense ball, so that when it hits the egg, it can penetrate. And in order for this DNA to be tightly packaged, the histone proteins must be replaced by other basic proteins.” The basic proteins include transition nuclear protein 1 (Tnp1) and protamine 1 (Prm1), said Zhang.

The researchers’ experiments established that the Jhdm2a demethylase specifically activates the Tnp1 and Prm1 genes. It does so by binding to the promoter region of the genes, which removes the methyl group that had been keeping the genes silent. Once the methyl group is removed, the Tnp1 and Prm1 genes are activated.

Zhang said that although their study was done in mice, it might well have implications for understanding some forms of human infertility. “It has been shown that there are many genes in mice that cause infertility when knocked out. But so far few of those genes has been found to be linked to human cases of infertility,” he said. “However, no one has paid much attention to these demethylase proteins. And since they play such a fundamental role in gene regulation in both mice and humans, there is a possibility that Jhdm2a plays a role in some types of human infertility.”

Zhang said that drugs that affect the Jhdm2a enzyme might have clinical use. “A small molecule that enhances the enzyme’s activity could be a useful fertility drug in cases where compromised function of the gene has caused infertility,” he said. “On the other hand, a small molecule that inhibits the enzyme’s activity could be a potential birth control drug.”

At Overlake Reproductive Health, passive 13.56 MHz RFID tags and interrogators track human sperm, eggs and embryos throughout the assisted-reproduction process.

By Claire Swedberg
RFID Journal
Copyright RFID Journal LLC 2008, Used With Permission

Oct. 15, 2007—Overlake Reproductive Health, located in Bellevue, Wash., has become the first reproductive-medicine center in the United States to deploy an RFID-based system for tracking human eggs, sperm and embryos. This system should help ensure that no identity mistakes are made during collection, storage and fertilization.

A female client can visit the clinic to be artificially inseminated by a partner’s sperm, or to have her egg fertilized in vitro (in a test tube) and then implanted in her uterus. For either procedure, the couple may worry that the sperm or egg might be accidentally switched with someone else’s, resulting in a baby that is not biologically theirs. Although such mistakes rarely happen, the experience can be traumatic for parents when they do occur, subjecting a clinic to lawsuits and negative publicity.

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Shaun Kelly

Until the RFID system was deployed in September, Overlake, like other in vitro fertilization (IVF) clinics, relied on the diligence of its employees to ensure that samples were never confused. When a patient provides sperm or eggs, the specimen is marked with the client’s name, and if transferred to another receptacle, it is again marked with that patients’ name. Usually, two employees manually check the names to prevent a mistake from being made. That system had been working appropriately, says Overlake’s laboratory director, Shaun Kelly, but patients were still uneasy.

At a recent American Society for Reproductive Medicine (ASRM) conference, Kelly happened upon Research Instruments, a U.K. manufacturer of RFID solutions, and saw a potential solution. “I was really intrigued by the whole thing from the get-go,” he says. Research Instruments provided Overlake with IVF Witness, an RFID-based system that helps keep specimens from being inadvertently switched.

Upon arrival, a patient is provided an ID card containing a 13.56 MHz RFID chip complying with ISO standard 15693. A staff member at the front desk inputs data about the patient, and a Research Instruments RFID interrogator captures the ID card number, which is linked to that data.

Each specimen is placed in a container with an RFID tag affixed to its bottom. When the container is placed on an interrogator, the system prompts the user to assign a particular patient to that specimen. IVF Witness permanently links the container’s tag ID number with that patient, so that the tag numbers for both sperm and eggs are input into the same patient account. When a specimen is sent to a lab, it passes several workstations, each equipped with an RFID reader. There are three readers in the sperm-prep lab; two in the embryology lab, where eggs are fertilized and developed; and one in the procedure room, where eggs are removed from a female client, and where sperm or embryos are implanted in the patient’s uterus.

At every step in the process, each specimen container is placed on a plate with an RFID reader, which captures the container’s tag ID. IVF Witness opens that patient’s account, and if any specimens tag IDs do not belong to that account, the system transmits an alert, emitting an audible alarm and displaying a red stop sign on the workstation screen. When this happens, the system cannot be restarted until an explanation is input to the system.

“The patients are incredibly happy with it,” Kelly says. New patients in particular, he adds—who have not yet had the opportunity to build a level of trust with the Overlake staff—find the RFID system reassuring. According to Kelly, Overlake continues with its original practice of hand-marking each specimen and using two witnesses to ensure the owner’s identity, but now it also has another layer of security. Although no situation has yet caused the system to issue an alert, Kelly says, the medical center has tested the system repeatedly and it is functioning properly.

“It is expensive,” Kelly says, citing the system’s price tag of nearly $60,000, and the clinic has had to extend some of that cost to clients. “They’re not complaining,” he notes. “They’re happy to have that security.”

Overlake typically completes up to 500 embryonic procedures annually. The system does not have FDA approval but doesn’t need it, according to Research Instruments. Still, the RFID system provider has tested it with mouse embryos to ensure that radio waves do not harm specimens. In Research Instruments’ tests, the tags transmitted continuously for four days without any perceptible effects on the mouse embryos.

RFID was chosen for this application, rather than bar-coding or some other technology, because it enabled a passive inventory check of the work area prior to the procedure being carried out, says David Lansdowne, technical director and patent holder at Research Instruments. With RFID, Lansdowne explains, lab personnel do not have to scan an item—they can simply place it on the workstation plate, and its ID number will be captured. Because automatic ID confirmation occurs as soon as a specimen is placed on the workstation, he says, a clinic “can ensure that laboratory SOPs [standard operating procedures] are being followed—something that is impossible with bar-code systems.”

Matthew Herper, 10.15.07
Forbes.com

Hugh Herr lost both his legs in a rock-climbing accident when he was 17. Now he plans to someday run faster than anyone ever has: on a pair of robotic legs.

Don’t bet against him. Six months after losing his legs, Herr was rock-climbing almost as well as before on prosthetics he modified himself. Now an associate professor at the MIT Media Laboratory, Herr designed the first robotic knee ever to make it to market–it’s sold by Iceland’s Ossur–and has just finished up the first replacement ankle that’s as strong as one of flesh and blood. It is only a matter of time, he says, before amputee athletes can routinely run faster and jump higher than Olympians.

Already, scientific advances may be driving the record books. Performance-enhancing drugs, including steroids for strength and EPO for endurance, are used in sports from cycling to baseball, with only draconian testing policies keeping them at bay. What happens if they became an accepted part of sports?

In Pictures: The Making Of A Super-Athlete

Tufts University physicist Roger Tobin, who has tried to put some numbers on the problem, says performance-enhancing drugs actually deliver less bang per dose than you’d expect from a relatively small increase in strength. At the highest levels of sport, it’s enough. “It could be the difference between the bronze medal and the gold, or the world record or not,” he says.

Tobin estimated that over a career, a baseball player using steroids could up his muscle mass by perhaps 10%. That would increase the speed of his bat by 4%, and the speed of the ball by 3%. For the top batters in the game, that tiny boost in power increases the number of balls hit out of the park by 50% to 100%. Given the potential side effects of these chemicals, we don’t want athletes using them. However, it’s no surprise they do.

Steroids are just the beginning. A drug being tested by Wyeth for muscular dystrophy blocks myostatin, a protein that prevents muscle from being created. Animals that use these same compounds grow incredibly large muscles, as did an infant with a mutated version of the myostatin gene. Already, dietary-supplement companies have been selling algae-derived medicines they say do the same thing–with no real evidence.

And a molecular switch inside cells called a peroxisome proliferator-activated receptor (PPAR) delta is involved in unknown ways with metabolism. “Marathon mice” that have had the PPAR delta receptor altered through genetic engineering can run for twice as long as their unmodified brothers and sisters. Drugs that turn up PPAR delta are in testing for the treatment of diabetes, but this has been a difficult area of drug development, because drugs to hit these mysterious receptors often have side effects.

The ultimate shift will come if science learns how to directly edit an athlete’s DNA, making him or her physically better without the need for drugs. So far, gene therapy, which aims to do this using modified viruses and other technology, has not panned out as a treatment. If it ever does, it could make the jobs of anti-doping associations far more difficult.

Replacement limbs that outperform real ones are far in the future, but some athletic associations are already worrying. Oscar Pistorius, a South African double-amputee and champion sprinter, has been fighting to compete against able-bodied athletes. But in July, the International Association of Athletics Federations, which is the arbiter at track-and-field events, said it needs “future research” to determine whether Pistorius, 21, has “advantages as a result of his prosthetic blades.”

The running prosthetics being developed in Herr’s lab don’t really have to be better than real legs, which need to be able to walk, climb and sit. They just need to be able to run, and they don’t need to be pretty either. Aimee Mullins, a double amputee who became a National Collegiate Athletic Association sprinter, told a recent Media Lab conference that at one point she wanted normal legs, but then she “got the bug. I wanted this stuff that came out of NASA.”

Herr wants to change the way people underestimate others who are different, and perhaps overestimate themselves. “Most people view the human as the center of the universe in terms of form and function,” he says. “They take something as basic as walking and running, and they have an amputee they pity and look down on run faster than they do … that’s mind-changing. That change in mindset about how people view others with different bodies is very important to society.”

That big change in mind-set could affect sports too. If human anatomy is no longer the center of the universe, would it be more fun to watch the athletes who can jump higher? Sure, it seems unlikely that people will have their legs replaced. But Herr’s lab is also working on exoskeletons that can help people carry 100 pounds without assistance. Someday, they might also allow athletes to traverse rough terrain–Herr predicts people will throw out their mountain bikes.

Imagine it: football games played on rocky mountainsides, or baseball with an obstacle course in the middle of the field. A skilled athlete would still do better than an unskilled one, but the exoskeletons would bring the game to an undreamed-of level. Says Herr: “It’s going to be fun as hell.”

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