Sunday, March 20, 2011

Biomedical Cooptation of the Psychosocial Care and Support Continuum for Severely Distressed Persons

Abstract:
In this issue of Ethical Human Sciences and Services, Lehrman describes his vision, focusing on continuity of care, of a mental health care system for psychosis. His main argument is that the same psychiatrist should treat an individual patient whatever the settings (hospital, community) that the patient shifts through, and that the psychiatrist is the key treating professional and as such should manage and direct care over the continuum. While continuity of psychiatric care is desirable and indeed noncontroversial and feasible, psychiatric services are not central to the care continuum, and its psychiatric control will lead to an even more biomedical orientation in patient care. This would undermine another key aspect of Lehrman's vision: a mental health system focused upon the whole person in interaction with the environment. The history of psychiatry shows that, as a medical specialty, psychiatry will inevitably focus upon the brain rather than the person. Psychiatric care could serve as adjunct to appropriate supports, services, and treatment, but if it determines them, they will merely become a downplayed accessory of biomedical (i.e., psychotropic drug) treatment.
Document Type: Miscellaneous
Affiliations: 1: CLSC Haute-Ville-des-Rivières (GRIOSE-SM) and Laval University Québec City, Canada
Publication date: 2003-01-01

Biomedical treatment autism (DAN doctor)

I am a physician specializing in the biomedical treatment of autistic children. I have offices in arizona , nevada, and california. I need articles to post on my website trinityalternative.com relating to the biomedical treatment. Articles can be on the special diets, SCD, GFCF, low oxalate etc, yeast treatment, testing, treatments or other relavant issues. I think the best qualified person has an autistic child and is doing the biomedical treatments. This is very specific and i hope i can find the some qualified writers. I do not have the time to write what i need because i am extremely busy with patient care. I have two M.D. degrees, one traditional allopathic and i am the only Homeopath who combines these skills to treat patients.

Geoffrey P Radoff, M.D., M.D. (h)

What is Biomedical Treatment?

Childhood neurological disorders (NDs) are typically diagnosed by professionals with psychology and psychiatry backgrounds. Parents are often told that their child’s diagnosis is the result of genes and is psychological in nature. Typical “psychological” manifestations of these NDs in children may include delayed speech, lack of eye contact, impaired or non-present social skills, shyness, perseverative behavior (doing the same thing repeatedly), delayed gross or fine motor skills, sensory integration issues (sound and touch sensitivity, etc.), not responding to one’s name, inflexibility with transitions, and major, often unexplained, changes in mood.
Yet, the physical or medical issues that these children often share are rarely noted or discussed. Typical physical manifestations of children with NDs may include food allergies and eczema, general gastrointestinal distress, constipation and diarrhea, yeast overgrowth, immune system disregulation, and sleep disturbances. Typically, proper testing also reveals high levels of environmental toxins relative to neurotypical children.
What has happened to our children? We believe our children’s bodies are overwhelmed by a combination of heavy metals (mercury, lead, aluminum, etc.), live viruses (particularly from vaccines), and bacteria. These toxins serve to slow or shut down normal biochemical pathways in the body and lead to the physical and mental manifestations we call NDs. Perhaps the best description of what happens to our children is Autism: A Twisted Tale of Virus and Thimerosal, by Dr. Amy Yasko.
Biomedical intervention for NDs is based on the belief that the psychological symptoms of NDs are a product of the physical issues the child is experiencing and that addressing the physical issues will lead to an improvement in the psychological symptoms. (We were very pleased to read the recent cover story in Discover magazine that clearly spells out that autism is “not just in the head” but may actually originate in the gut and from environmental toxins.)
The following is our best attempt to get you started on the path to healing your child. This is not medical advice. It is the opinion of parents, not doctors. The most important thing you can do as a parent is find a qualified physician to help you treat your child. All that is written here is for informational purposes only.
The ultimate goal of biomedical treatment is to remove environmental toxins from your child’s body and repair the damage that has been done. Today, there is a bewildering array of potential treatment modalities for parents to follow. Some of the most popular include:
The DAN Protocol. DAN, or Defeat Autism Now!, is a project of the Autism Research Institute. The DAN Protocol is not a clear and explicit protocol, per se, but rather a general approach to treating children that is being followed by a group of doctors known as DAN doctors. The best resource to get a background in the DAN approach is the book Children with Starving Brains, written by Jaquelyn McCandless, MD, a DAN doctor. A complete list of DAN doctors is available at www.autism.com/dan/ danusdis.htm. DAN Conferences are held for parents twice a year. Yahoo discussion groups that include parents working with DAN doctors include ChelatingKids2 and ABMD.
The Cutler Protocol. Andy Cutler is a scientist who developed a protocol for removing heavy metals from the body. His protocol is detailed in his book, Amalgam Illness, and through the Yahoo discussion group Autism-Mercury. Many of the parents using the Cutler Protocol to remove toxins from their child’s body are also using a DAN doctor and many of the DAN approaches to treatment.
Dr. Amy Yasko. Dr. Yasko’s approach to treating children with NDs has many similarities to DAN, but focuses treatment on the specific genes of the child, providing a roadmap that some parents believe is more customized. Her approach is also more focused on the removal of viruses and bacteria from the child’s body. Learn more through her websites, www.dramyyasko.com and www.holistichealth.com, her parent discussion group, and her book, The Puzzle of Autism: Putting It All Together.
Michael Lang’s Natural Detoxification Program. Michael Lang is the founder of Brainchild Nutritionals, a supplement company serving children with NDs. Recently, he published a helpful guide with his own recommendations for how to detoxify a child with an ND safely and effectively.
Methyl B12 and Valtrex. A number of parents have experienced particular success using a combination of Methyl B12 (a vitamin) and Valtrex (a prescription drug that suppresses viruses). This approach has been spelled out by a parent who recovered his son from autism, Stan Kurtz.
Homeopathy. Many parents report great results using homeopathy. The best description of this approach is available in a book written by a parent, The Impossible Cure. Also, check out the discussion group run by the Homeopathy Center of Houston serving children with NDs.

Most parents employ some combination of the above approaches in treating their child. It can be frustrating for a parent to realize how varied the treatment approaches can be, which is why it’s critical to find a doctor to work closely with to find the right approach for your child. Reading about biomedical treatments for NDs is very overwhelming and it is helpful to keep the “big picture” in mind. The 4 most important things you can do to help heal your child are:
1. Bring down the toxin load.
2. Help the gut heal.
3. Get the nutrients up.
4. Get the metals and other toxins out.

Autism Treatment - Biomedical Treatments for Adults With Autism

I would like to talk a little bit about something with respects to adults who are on the Autism spectrum. The issue is the word "cure" that has been used within the biomedical community for several years. Not all doctors use the word cure but also some individuals who use the word cure as a goal or potential for those with Autism. I understand that the use of this word has created controversy and/or sparked anger within our Autism community, especially from adults who have Autism.
I want to state my perspective clearly, I have never used the term "cure" in any of my dialog regarding the biomedical treatments for Autism. While I have seen people "recover" from the underlying medical issues they were dealing with, the term "cure" implies a complete change of the underlying personality or the issues that are occurring in someone with Autism. I choose not to use that word and can certainly understand the frustration or disagreement some individuals with Autism have with its use.
I see biomedicine as more than just a diet, giving supplements, or giving certain medications. It really is about exploring the clinical health of an individual. And many times there are underlying issues that need to be addressed like biochemical imbalances, vitamin and amino acid deficiencies, dietary allergies, digestive problems or whatnot, and when they are addressed you see changes in cognition and improvement in their quality of life, whether they are a child, teen or adult with Autism. We are talking about optimizing someone's health, not "cure", and to me, there is nothing wrong with trying to optimize someone's potential. I believe that improving the overall health of an individual should be the focus of every health pursuit, not to alter someone's personality. When you make these changes you find that the brain, immune system, gut, heart, lungs and body all function better.
The fact is that many people with Autism suffer from, for example, issues with their digestive tract. By addressing those issues you don't have "recovery" necessarily but you do have an individual who feels better. And when you decrease pain and discomfort in their gut, they can then digest food better and they have less bowel issues and function better. It almost goes without saying that if you remove the physical pains, you can increase mental capacity and mental harmony.
So I wanted to talk about these issues in adults with Autism because I mostly see children in my practice but I have worked with adults who face the same health challenges as the children. And occasionally I will see an adult with Autism who has a child on the spectrum as well which then can show you just how much these things go hand in hand. So it is all about optimizing health, improving function so that the individual is able to reach their full potential, whatever that may be. We don't have to use the term "cure" but rather we can talk about the improvement in health and functionality.
Autism really is treatable! Biomedical Autism treatments and therapies have resulted in many, many children improving, or even even losing their autism-spectrum disorder diagnosis. For lots more free biomedical autism intervention information and videos from Dr. Woeller, go to http://www.AutismRecoveryTreatment.com.
Dr. Kurt Woeller is an biomedical autism Intervention specialist, with a private practice in Southern California for over 10 years. He has helped children recover from autism, ADD, ADHD, and other disorders, and has the information you need to help your child. Download his free ebook at http://www.AutismActionPlan.org.

Recognizing speculative language in biomedical research articles: a linguistically motivated perspective Citation: BMC Bioinformatics

Abstract Background Due to the nature of scientific methodology, research articles are rich in speculative and tentative statements, also known as hedges. We explore a linguistically motivated approach to the problem of recognizing such language in biomedical research articles. Our approach draws on prior linguistic work as well as existing lexical resources to create a dictionary of hedging cues and extends it by introducing syntactic patterns. Furthermore, recognizing that hedging cues differ in speculative strength, we assign them weights in two ways: automatically using the information gain (IG) measure and semi-automatically based on their types and centrality to hedging. Weights of hedging cues are used to determine the speculative strength of sentences. Results We test our system on two publicly available hedging datasets. On the fruit-fly dataset, we achieve a precision-recall breakeven point (BEP) of 0.85 using the semi-automatic weighting scheme and a lower BEP of 0.80 with the information gain weighting scheme. These results are competitive with the previously reported best results (BEP of 0.85). On the BMC dataset, using semi-automatic weighting yields a BEP of 0.82, a statistically significant improvement (p <0.01) over the previously reported best result (BEP of 0.76), while information gain weighting yields a BEP of 0.70. Conclusion Our results demonstrate that speculative language can be recognized successfully with a linguistically motivated approach and confirms that selection of hedging devices affects the speculative strength of the sentence, which can be captured reasonably by weighting the hedging cues. The improvement obtained on the BMC dataset with a semi-automatic weighting scheme indicates that our linguistically oriented approach is more portable than the machine-learning based approaches. Lower performance obtained with the information gain weighting scheme suggests that this method may benefit from a larger, manually annotated corpus for automatically inducing the weights.

Biomedical model

The biomedical model of medicine, has been around for centuries as the predominant model used by physicians in the diagnosis of disease. The term is used by practitioners of Natural Health, a form of alternative medicine, in contrast to the biopsychosocial model, which incorporates psychological and social factors.

This model focusses on the physical processes, such as the pathology, the biochemistry and the physiology of a disease. It does not take into account the role of a person's mind or society in the cause and treatment.
This model is effective at diagnosing and treating most diseases. It cannot be denied that it has been extremely useful throughout history by establishing the reasons that a disease occurs, and in coming up with very effective treatment regimes.
It is however very limiting. By not taking into account society in general, the prevention of disease is omitted. Many diseases affecting first world countries nowadays, such as heart disease and diabetes mellitus are very much dependent on a person's actions and beliefs.

Citation in biomedical journal articles

Abstract

To determine how biomedical scientists use the published work of others in their journal articles, the first two references, source articles, were compared to their citing article in seven citation trees containing 49 experimental or descriptive articles. In addition, a group of practicing biomedical scientists was surveyed to discover their perceptions of citation practices. Although five scientists mentioned the use of direct quotation, only two trivial instances, from a single author, were found; paraphrase was limited to three authors; the majority of instances were summary from a single source or generalization from two or more. For journal articles, only the latter two citation types need be taught to novice writers. Because students may be tempted to use others' wording, it may be advisable to teach paraphrase, while taking care not to recommend it. Teachers are advised to acquaint students with a range of ethical questions.

Article Outline

• References
* Betty Lou Dubois received her Ph.D. in 1972 from the University of New Mexico Program in Linguistics and Language Pedagogy. Since then she has taught at New Mexico State University, where she is now Professor of Communication Studies, TESOL Coordinator, and head of the MA program. Her major research interest is biomedical communication, both written and spoken, including its sociological aspects.

What is BioMedical Engineering OnLine?

BioMedical Engineering OnLine is an Open Access, peer-reviewed, online journal that is dedicated to publishing research in all areas of biomedical engineering.
BioMedical Engineering OnLine is aimed at readers and authors throughout the world with an interest in using tools of the physical sciences to advance and understand problems in the biological and medical sciences. There are biomedical engineers in countries throughout the world, and the results of their work are scattered and often difficult to access. This publication promotes the rapid and free accessibility of articles for biomedical engineering researchers everywhere. The result is a worldwide community of biomedical engineers who are linked together by their various research interests and their values in promoting benefits to all of humanity.
Content overview
BioMedical Engineering OnLine considers the following types of articles:
  • Research: presenting new work based on the highest standards of basic or applied academic research.
  • Book reviews: presenting short summaries of the strengths and weaknesses of a book. They should evaluate its overall usefulness to the intended audience. Please contact Francisco Azuaje (fj.azuaje@ulster.ac.uk) with your Book review proposal.
  • Letters to the Editor: can take three forms: a substantial re-analysis of a previously published article, or a substantial response to such a re-analysis from the authors of the original publication, or an article that may not cover 'standard research' but that may be relevant to readers.
  • Reviews: presenting a comprehensive and authoritative description and evaluation of a current scientific or research area within the journal scope, these articles are usually written by opinion leaders that have been invited by the Editorial Board.
Peer review policies
All articles are reviewed by at least three experts from the relevant field. The reviewers consider the technical aspects of the material presented, in terms of scientific validity and usefulness. Authors are given every opportunity to alter their submission and/or to respond to the comments.
Edited by Kenneth R. Foster, BioMedical Engineering OnLine is supported by an expert Editorial Board.
Publishing in BioMedical Engineering OnLine
All articles are listed in PubMed immediately upon acceptance (after peer review), and are covered by PubMed Central, MEDLINE, Thomson Reuters (ISI) and Embase.
Articles in BioMedical Engineering OnLine should be cited in the same way as articles in a traditional journal. However, because articles in this journal are not printed, they do not have page numbers. Instead, they have a unique article number.
The following citation:

BioMed Eng OnLine 2004, 2:1

refers to article 1 from volume 2 of the journal.
As an online journal, BioMedical Engineering OnLine does not have issue numbers. Each volume corresponds to a calendar year.
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Manuscripts should be submitted electronically to BioMedical Engineering OnLine using the online submission system. Full details of how to submit a manuscript are given in the instructions for authors.
General journal policies
BioMedical Engineering OnLine is published by BioMed Central, part of Springer Science+Business Media. BioMed Central is committed to ensuring peer-reviewed biomedical research is open access. That means it is freely and universally accessible online, it is archived in at least one internationally recognised free access repository, and its authors retain copyright, allowing anyone to reproduce or disseminate articles, according to the BioMed Central copyright and licence agreement. BioMedical Engineering OnLine however, has taken this further by making all its content open access.
BioMedical Engineering OnLine's articles are archived in PubMed Central, the US National Library of Medicine's full-text repository of life science literature, and also at INIST in France and in e-Depot, the National Library of the Netherlands' digital archive of all electronic publications. The journal is also participating in the British Library's e-journals pilot project, and plans to deposit copies of all articles with the British Library.
BioMedical Engineering OnLine is able to deliver summaries of frequently updated content via Really Simple Syndication (RSS) feeds. These are accessible via the orange "XML" button at the top of the list of recent articles or the list of most accessed articles. For more information about RSS feeds see our publisher's website.
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Tuesday, March 15, 2011

New Drug Shown Effective in Blocking HIV Entry

A research team led by Dr. Pin-Fang Lin at Bristol-Myers Squibb, Wallingford, CT has discovered a small molecule compound that can block HIV-1’s entrance into cells (Lin, P.-F. et al., PNAS 100:11013-11018, Sep. 16, 2003). Most of the drugs currently available for treating HIV infection affect replication of viral nucleic acids or the synthesis of viral proteins.
The compound, BMS-378806, binds to the envelope protein, gp120, of HIV-1 and inhibits interactions between gp120 and the CD4 receptor molecule on CD4+ T cells, a necessary step for HIV-1 to infect host cells.
The inhibitory effect of compound BMS-378806 is selective for HIV-1. It is inactive against HIV-2 (a less virulent, primarily West African virus similar to HIV-1), simian immunodeficiency virus, and other viruses tested. The compound exhibits other encouraging pharmacokinetic amenities such as low protein binding and minimal impairment of the compound by human serum. Tests in animals showed that the compound is safe, with acceptable toxicity profiles.
The compound targets a specific HIV-1 protein that does not exist in human cells. It is a novel approach for HIV-1 therapies. It represents a hope that HIV-1 can be stopped before it infects cells. This class of drugs can be used in combination with other drugs to achieve maximum deterrence of HIV-1 infection.

Three trials with strong financial supporters test Viread as a preventive drug for HIV infection

Three clinical trials starting this year will test the effectiveness of Viread (tenofovir disoproxil fumarate) in preventing HIV. Viread, a nucleotide reverse transcriptase inhibitor, is currently approved to treat patients already infected with HIV. Clinical studies showed that Viread is relatively less toxic and less prone to the development of resistance towards it. Gilead Sciences, Foster City, CA makes and markets Viread since 2001 with estimated sales of $550 to $570 million in 2003.
Several years ago, a research team headed by Dr. Roberta Black at the University of Washington’s Regional Primate Research Center in Seattle, published a report in Science demonstrating Viread’s effectiveness in preventing simian immunodeficiency virus (SIV) infection in monkeys (Tsai CC et al., Science 270:1197-1199, Nov. 17, 1995). The effectiveness of Viread [then called (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA)] was tested both pre- and post-exposure in preventing SIV in macaques as a model for HIV prevention in humans. Viread was administered beginning 48 hours before, 4 hours after, or 24 hours after virus inoculation. The once daily treatment was continued for 4 weeks. Virologic, immunologic, and clinical parameters of the macaques were monitored for up to 56 weeks. Viread prevented SIV infection in all macaques without toxicity, whereas all control macaques became infected. The results indicated that Viread was able to prevent the SIV infections in monkeys and suggested that it may have similar effects on HIV in humans.
The Bill and Melinda Gates Foundation will pay $6.5 million to test Viread in 2,000 people in Cambodia, Ghana, and other countries. The U.S. National Institutes of Health has awarded a $2.1 million grant to the University of California to evaluate Viread in 960 Cambodian women including many at-risk prostitutes. The U.S. Centers for Disease Control is paying $3.5 million for testing in 400 uninfected gay and bisexual men.
HIV has so far infected about 40 million people worldwide and is spreading rampantly in parts of Africa and Asia. Because it does not have to be taken repeatedly, a vaccine would be a more effective means to slow the rate of transmission but development has proven elusive and no vaccine is predicted to be available for at least the next decade. At the present time, a drug may be the best means to slow the spread of HIV.

Recent Advances in Biopolymers and Biomedical Materials

In this overview of recently published scientific literature, the authors provide a snapshot of current research trends in biopolymers and biomedical polymers. During experimentation to improve product benefits, the personal care industry eagerly formulates with new and different materials and ideas. Sometimes these new materials are generated within the industry while other times, they are borrowed from other sectors. In reviewing the current scientific literature, the authors hope to encourage readers to innovate by technology transfer and by gaining a better understanding of biopolymers at a time when they are escalating in importance.

A Biomedical Look At Spaceflight

Mary Roach, author of previous entertaining books Bonk (a history of sex research) and Stiff (a history of cadaver research), has turned her considerable talents in translating decades of research into a readable review of human (and animal) spaceflight experimentation.
The title of her new book, Packing for Mars: The Curious Science of Life in the Void, is a bit of a misnomer — only the last chapter is devoted to the medical advances needed for a trip to Mars. However, it is a great layman’s history of the biomedical results of both the American and Russian space programs.
Through my own research and academic career I’ve been peripherally involved with many of the recent studies she mentions in the book, and I know many of the people she interviewed, so I give her credit for taking some fairly complicated concepts and distilling them to relevant anecdotes and asides.
Her characterizations of the individuals I know is spot on and I can hear their voices in the quotes she uses. Roach breaks the book down roughly into large projects, rather than by physiological areas or research fields, such as cadaver tests for the next space capsule, space food packaging, simulated environments, microgravity flights, Japanese astronaut selection, porn filmed partially in microgravity, and nausea experiments.
Each chapter typically focuses on some large effort and builds context by peppering in the results from other studies and an interviews with experts in the field. The resulting chapters are pretty independent and, aside from a transition paragraph at the end of each, could probably be read in any order. This style of writing is familiar to anyone who has read Roach’s other books.
Roach accurately notes NASA and the space program’s role in the development of medical technology, although the NASA Public Affairs Office may put it differently when promoting the positive benefits of space flight; NASA sees medical technology as a means, not an end. She mentions that most medical technology that helps increase efficiency, redundancy, reliability, or decrease size, mass, and power requirements were worked on or considered by NASA and related agencies at some point. Not because NASA’s charter includes helping the world, but because it helps get more stuff off the ground with the constraints inherent in spaceflight.
The book includes interviews with researchers in the National Space Biomedical Research Institute (NSBRI), a group we have mentioned many times here on Medgadget, which functions as NASA’s academic research arm. NSBRI researchers tend to be a little easier to talk to about the topics Roach covers in the book, mostly because they don’t have to go through NASA Public Affairs. [Disclosure: My thesis work has been partially funded by both NASA and NSBRI, so I have a sense of the bureaucratic issues, and there are many.]
Overall, I would recommend this book to anyone interested in what the body goes through in spaceflight, and how we are preparing for those challenges. Regardless of familiarity with the subject matter, Mary Roach’s book is informative and entertaining, showing a well-thought out perspective on medical research in spaceflight.
Link: Packing for Mars: The Curious Science of Life in the Void
*This blog post was originally published at Medgadget*

Biomedical Autism Treatment – Exercise and Autism

I want to talk a little bit about the role of exercise and treatment of Autism. Some recent information has come out that discusses how exercise impacts depression. What research seems to be finding is that for individuals who get regular exercise, which means at least 30 minutes per day, 3 to 5 times per week, they had significantly reduced rates of depressive issues, by 45%. And given that in our country we primarily treat depression using ant-depressive medications, this new information is very significant. Just simply getting enough aerobic exercise each week, 30 minutes a day and between 3 and 5 days per week, can reduce depression significantly.

Over the course of treating children in my practice for years, I too have seen the benefits of children with Autism who get regular exercise. They seem to function better, that can mean better behavior, better attention, better focusing, less anxiety, etc. And yet for children, the definition of exercise can be different than that of an adult. Going to a park and letting them run and play on the equipment can be great exercise. They have the opportunity to run, climb and swing. Another wonderful activity for kids is riding their bike. Swimming is also a great activity, as is just about anything that lets them be physically active. I really do encourage parents to let their children get out in the fresh air and natural sun light, especially now that summer is here and the days are getting longer. Let your child explore, play and run if that is something that they seem interested in.

We see more and more children who spend most of their time inside, usually stuck on the computer or stuck on video games or watching movies. And many children with Autism spend many hours a day in therapy sessions. After their therapy sessions they can tend to be anxious, hyper, agitated, and have trouble sleeping. What can make a world of difference is making sure your child also gets some exercise. A nightly walk after dinner can be a great place to start. And remember, it is not all about supplements, it is not just about medications, it is not just about a diet. Sometimes a change in attitude comes from good physical exertion and physical exercise, it can put your child with Autism in a better mental state.

Who’s afraid of the recent biomedical heritage?

As biomedicine – the fusion of cell biology, molecular biology and information technology with clinical diagnostics and therapeutics – is emerging as a significant part of contemporary society and culture, it is time for university museums to take biomedicalization seriously. The Medical Museion at the University of Copenhagen is presently trying to resolve the museological problems that are raised in making sense of recent biomedical artefacts. Traditionally, museums deal with tangible material objects: good medical museum artefacts are concrete, sensual and spectacular, they are immediately understandable; they elicit memories, and evoke emotions. The emergence of recent biomedicine, however, challenges this classical notion of material objects as familiar, tangible, and sensuous. Today’s biomedical objects are abstract, non-tangible, and difficult to understand; they elicit few memories and hardly evoke any emotions. The challenges of recent biomedicine to university museums are illustrated with reference to three examples: gene microarray analysis, PET scanning, and molecular therapy. The paper concludes that medical museums today are caught in a paradox. On the one hand, biomedical research and technology fills more and more of our lives, from neonatal care to terminal intensive units. On the other hand, the whole idea of what constitutes a medical museum collection and what is displayable and easily understood by visitors in a medical museum exhibition becomes questionable.
Medicine is one of the oldest and most venerated ingredients of the world’s cultural and scientific heritage. Consequently medical artefacts feature prominently in many university museum collections. With respect to the historical time range covered, however, almost all museums deal with what might be called ‘modern medicine’, that is, they mainly contain artefacts and ideas that represent the medical practices of the modern era, from seventeenth century anatomical specimens to late-twentieth century mechanical medical instruments. With few exceptions, museums have not yet taken the rapidly growing biomedical culture of our present age into account, and so far no museum has made systematic efforts to document the recent biomedical heritage.
I suggest it is time for university museums to take biomedicine — that is, the fusion of cell biology, molecular biology and information technology with clinical diagnostics and therapeutics — seriously. The reason is, of course, that biomedicine is emerging as a significant formative part of contemporary society and culture. The discovery of the structure of DNA in 1953 and the subsequent rise of molecular biology have radically changed the research agendas, strategic decisions, and curricula of medical faculties over the last decades. A rapidly growing number of new molecular technologies have changed diagnostic and therapeutic methods beyond recognition; today’s clinical biochemical laboratory is a highly sophisticated and robotized molecular diagnostic system and gene therapy is becoming clinical reality. Digitalization too has changed biomedical research and clinical practices drastically in the last decades. Medical research is highly dependent on computerized methods. Clinical departments like neonatal wards or intensive care units are as digitalized as the cockpit in a modern aircraft. Diagnostic imaging tools like CT-, MR- and PET-scanning would be impossible without advanced digital technology.
This combined process of molecularization and digitalization of the laboratory and the clinic (in other words, biomedicalization) is embedded in a broader social and cultural context. The many (and often politically mediated) interactions between the transnational ‘biomedical-industrial complex’ and the steadily growing popular demand for better health care are turning biomedicine into a significant player on the global economic arena. Biomedicine has also entered the political scene. While some view its recent developments as a threat to basic human values, others see it as a key to the future of humankind. New technologies such as stem cell manipulation, cloning, and tissue engineering have raised both professional and popular expectations of the powers of biomedicine to combat, for example, cancer and degenerative diseases.
How can university museums accommodate to these material and discursive changes in the medical landscape? What consequences will the recent revolution in biomedical research and clinical development have for medical history collections and exhibitions? In the Medical Museion at the University of Copenhagen we are presently trying to resolve these and similar questions. In this paper I will discuss one of the museological problems raised, viz., how to handle the abstract and non-tangible character of many recent biomedical objects.
The Medical Museion is the continuation of the Medical History Museum in Copenhagen, founded by a private initiative in 1906. The rapidly expanding collections were taken over by the university in 1918, and thirty years later they were moved to their present location in the former Royal Academy of Surgeons and adjacent buildings. Today the University of Copenhagen owns one of the largest and most diversified medical history university collections in the world, including thousands of obstetric, radiological, opthamological, dental, and surgical instruments, several complete apothecaries and old pharmaceutical laboratories, an interesting assortment of microscopes, and a world-famous osteopathological collection from medieval leprosaria. Altogether the collections comprise approx. 60.000 registration units (a registration unit may contain many separate physical items so the number of individual objects probably exceeds a hundred thousand); in addition there are close to 100.000 iconographical items, a library of 30.000 volumes, and approx. 4000 archival units, including hospital patient records from the late eighteenth century and onwards. Only a small proportion of this material is displayed in the public exhibitions; most is kept in storage or in special ‘study collections’ for specialists.
Like most other medical university museums, the collecting and exhibition activities of the Medical History Museum were focused on ‘modern medicine’, especially on instruments that documented the triumph of the modern medical profession in the late nineteenth and first half of the twentieth century. But in recent years the museum has changed its orientation. The incentive for this move was the fact that the museum had stagnated since the 1970s; there were no research activities of any significance, the collections were run by amateur curators, and the exhibitions had not been revised for decades. A devastating report by The Danish State Board of Museums in 2000 raised negative headlines (‘Chaos in the museum’) in the Danish medical weekly, and induced the Faculty of Health Sciences to take its responsibility as owner. A year earlier, the chair in history of medicine had been filled to boost medical history research; in the following years three new museum positions were announced. Basic funding was increased as well, and in 2003 the faculty gave its unanimous support to a five-year plan for re-conceptualizing the former Medical-History Museum as a Medical Museion.
The Medical Museion concept is two-pronged. The basic idea is that research, teaching, collection activities and public outreach (including exhibitions) are closely integrated activities that mutually support each other. The classical notion of ‘museion’ has been chosen to symbolize the bridging of the gap between a traditional academic medical history research and teaching culture focusing on the production of texts (articles, books), and a traditional curatorial culture dealing with the acquisition, preservation and exhibition of material objects and images. In daily practice, this bridging means that both research and museum staff attend the weekly seminar dealing with all aspects of the institution, from registration systems and conservation methods to the history and philosophy of biology and the interaction between biomedicine and art; guest speakers include medical researchers, historians, ethnologists, museologists and artists. In other words, instead of making the traditional distinction between an academic university department and a museum, research, curating and acquisition are considered to be closely related forms of ‘inquiry’, and scholarly publishing, teaching and exhibitions are seen as closely related aspects of ‘presentation’.
The other main idea behind the Medical Museion concept is to shift the focus to the understanding, documentation and presentation of recent biomedicine in its social and cultural context. From the point of view of our university identity this shift of focus is advantageous as a growing number of conferences, monographs and research articles on different aspects of biomedicalization have appeared in the last decade. In other words, we are joining a growing trend among historians of science, historians of medicine, and scholars of science studies to investigate the recent history of biomedicine.
From the point of view of our museum identity, however, the new focus on recent biomedicine does raise some problems. With the exception of the Science Museum in London, very few museum institutions have taken the recent biomedical revolution seriously, and even fewer have begun to systematically acquire biomedical artefacts. Most medical history exhibitions still present medicine as it were in the period from the late eighteenth to the mid-twentieth centuries, that is, before molecular biology and information technologies began to change its face.
However, if (or rather when) museums begin to pay attention to recent biomedicine, they will be running into a major museological problem. This problem has to do with the object character of biomedical artefacts. Traditionally, museums are institutions that deal with material objects and material culture. The key-word here is tangibility — and medical museums are no exceptions, filled as they are with surgical instruments, microscopes, contraceptive devices, iron lungs, hospital beds, anatomical specimens, and so forth. Medical museum curators usually do not consider it a problem to define what an ‘object’ is, or what constitutes a ‘good’ museum object. Good objects are concrete, sensual and spectacular, like foot-driven dentist’s drills, siamese twins in jars, amputation saws, and trepanation instruments in handy travel sets. These and similar objects are considered ‘good’ objects because they are made of easily recognizable materials and resemble familiar tools; they are immediately understandable and also appeal to our fear of pain and death; they trigger the visitor’s attention, elicit memories, evoke emotions, and make us pause in front of the objects with a sense of curiosity and wonder. The lithoclast — an instrument invented in the early nineteenth century to crush bladder stones through the urethra (thus lowering the risk and pain of classical stone cutting) — is an archetypically ‘good’ medical history exhibition object. Young male visitors to the Medical Museion regularly turn pale when they realize how the instrument was used — before anaesthesia.
The emergence of recent biomedicine, however, challenges this classical notion of material objects as familiar, tangible, and sensuous. Today’s biomedical objects are neither familiar, nor tangible; neither sensuous, nor emotionally evocative. To illustrate the challenges of recent biomedicine to university museums, I will shortly discuss three cases: gene microarray analysis, PET scanning, and molecular therapy.
Microarray analysis is one of the most sophisticated methods in post-genomic medicine. Based on the fact that the degree of hybridization between single-stranded oligonucleotide molecules is a measure of their similarity, it uses arrays of hundreds of thousands of specific oligonucleotide sequences as probes to map an unknown RNA/DNA-sample; this makes it possible to gauge the gene expression level of the entire genome (that is, which genes are ‘on’ and which are ‘off’) in one single run. The analytical power of the method has ushered a rapid growth of expectations in the biomedical research community and the pharmaceutical industry to use it as a major diagnostic and therapeutic tool, for example for individualized drug treatment: ‘The explosion in interest in DNA microarrays has almost been like a gold rush’, proclaims a textbook in the field.
The most widely used and best known microarray platform, the Affymetrix GeneChip®, was invented in the late 1980s and came into industrial production a few years later. By combining information technology and molecular biology the GeneChip embodies the very essence of biomedicine. It illustrates the restructuring of health-care in the advanced post-industrial societies towards increased individualisation of diagnostics and treatment. Also, by drawing on globally produced and globally available sequence data bases it epitomizes another salient aspect of the biomedical revolution, viz., its integration in the process of globalization. Furthermore, as one of the few biomedical technologies that has made it to the front-page of Financial Times, the GeneChip is an example of how cutting-edge university research often has given rise to successful private enterprises (the ‘Silicon Valley effect’) over the last decades. Finally it reminds us of Peter Sloterdijk’s point that biotechnology, for better or for worse, can make the old vision of eugenics come true. The Affymetrix GeneChip thus provides an ample focusing point for historians of recent biomedicine and biotechnology.
For museums curators, however, the GeneChip poses a problem. What is immediately available for display is just the handy 1 x 2 inch plastic casing where the hybridization reaction takes place. The ½ x ½ inch ‘chip’ inside, with some half million oligonucleotide molecular-sized probes attached to it, is not immediately visible, or intelligible. The result of the test is only visible indirectly; the genome data are produced by reading the hybridization pattern on the chip with a laser scanner (which looks like an advanced coffee machine) and the result is interpreted by a computer program. It is hardly necessary to say that the GeneChip technology, which is now revolutionizing medical diagnostics, makes poor museum objects because all the components of the platform are abstract, intangible and hardly evoke any memories or strong emotional reactions.
The PET (positron emission tomography) scanner, too, illustrates the problem of displaying new biomedical artefacts in a museum exhibition. The instrument is built to produce images representing the inner metabolism of the body; information that is indeed useful for diagnostic purposes. The patient is injected with glucose molecules marked with a short-lived isotope that emits positrons that can be measured by a detector. The ensuing data are then interpreted by a computer program to represent slices (tomography) of the spatial distribution of glucose metabolism in the body on a screen. For example, the screen image of metabolism in the brain of patients with Alzheimer’s disease is significantly different from that in ‘normal’ patient brains.
The PET-scanner is an impressive piece of combined digital and molecular technology which has already had great impact on medical diagnostics. An update of earlier imaging technologies, like X-ray, as it were — and as such it is a ‘must’ in any museum that wishes to document and exhibit significant features of recent university medicine. But whereas X-ray technology is relatively easily understood in terms of ‘modern medicine’ and does not create any problems for medical museum curators, the PET scanner poses at least two museological problems.
One problem is that the PET scanner defies traditional museological display strategies. The directly visible and tangible ‘objects’ — the enclosing cabinet and the bed which the patient is placed on during the scanning procedure — are not at all important for the functionality of the scanner. The working material parts are either invisible and non-tangible (the isotope molecules) or non-intelligible (the detector and the computer hardware) and in addition do not make much sense without the resulting screen image. The ‘image’ in turn is indeed visible as long as the machine runs, but it is not tangible; it is the ephemeral result of the handling of signal data by the ‘text’ (that is, the computer programme code). The other problem (and this is why I have placed the words ‘object’, ‘image’ and ‘text’ between inverted commas) is that the PET scanner blurs the traditional categories of ‘object’, ‘image’ and ‘text’. How shall this artefact be classified? Does it belong among the physical museum objects? Or is it better placed (as an image) in the iconographical collection? Or even (as program code) in the archive?
My last example of how recent biomedicine is a challenge to university museums is the advent of molecular therapy. Traditionally, pharmacology is based on trial-and-error experience. The administered drug may not even be chemically characterized (as in folk herbal medicine) and physicians usually have no knowledge of the biochemical mechanism behind the effect; it just happens to work. Now, however, the biochemical mechanism that mediates between the active substance and the physiological response is being elucidated in a growing number of cases. A good example of molecular therapy is AstraZeneca’s Losec®, the world’s best-selling drug against ulcer and heart-burn in the 1990s. Earlier, ulcer patients were often treated with surgery; today they are given antibiotics against the Heliobacter infection and Losec to lower stomach acidity (often in the form of combination therapy).
The active substance in Losec is a synthetic molecule, omeprazol that specifically blocks the proton pump and hence acid production in the stomach. In other words, the omeprazol molecules work as a kind of specific biochemical microsurgery. It is thus a smart medical technology (and a major source of income for AstraZeneca) — but it is hardly a best-seller for medical museums. True, the Losec pill is tangible, but it looks very much like all other pills. The trillions of ‘molecular knives’ (omeprazol molecules) are intangible and invisible. The ion channels in the gastric lining are tangible on the microscopic level, but not visible to the naked eye. Furthermore, the most interesting ‘object’ is neither the pill nor the molecule, but the international network of scientists, medical doctors, advertising firms, and financial analysts who made a business success out of the omeprazol molecule. One could, of course, put the pill on a piece of black cloth under a spotlight and play a recorded deep voice telling the visitor that it gave AstraZeneca a 8 billion dollar revenue in the year 2000 only. But such stories are probably better told in books and magazines than in exhibitions. Likewise, the molecular and biological mechanisms of omeprazol may be better told in book pages and computer screens than in museums.
Microarray systems, PET scanners, and molecular therapies exemplify the problems involved in collecting and exhibiting recent biomedicine. Consequently I believe that medical museums today are caught in a paradox. On the one hand, biomedical research and technology fills more and more of our lives. On the other hand, the whole idea of what constitutes a medical museum collection and what is displayable in a medical museum exhibition is open to question, because medical diagnostics and treatment has become less visible and less sensuous. The biomedical ideas and artefacts of the last decades are very different from those presently gathered and displayed in museums. They are smaller (often microscopic), more abstract and mediated, less tangible (if not altogether intangible), and generally much less emotionally evocative than traditional ‘modern medical’ objects. And sometimes they are not even material artefacts in the classical sense, but ‘boundary artefacts’, that is simultaneously ‘material objects’, ‘texts’ and ‘images’, depending on the context of interpretation.
There may come a point when it becomes impossible to display such objects in a museum exhibition in any meaningful way. After all, who would come to the local university museum on a Sunday afternoon to read computer manuals, look at anonymous instrument plastic cabinets discretely labelled Perkin-Elmer or Hewlett-Packard, or watch video screens that represent repetitive patterns of DNA hybridization reactions? Will not those who are curious about the emergence of recent biomedicine and its impact on the world rather download the molecular images on their own computer or read about the global biomedical economy on a webpage or in a book or a magazine article instead? It makes sense to visit the local university museum to see lithoclasts, amputation saws, and siamese twins in jars? But why at all visit a museum if one wants to watch displays which elicudate the basic textbook principles of a PET scanner, a gene microarray or a ‘molecular knife’?
I believe this is a genuine museological problem and one that all museums with medical collections and exhibitions will have to solve in the near future — unless they want to restrict their activities to the safe realm of ‘modern medicine’. I am not pretending that the Medical Museion in Copenhagen has a solution in sight or even a smart way of circumventing it. But we are presently working on explicating and conceptualizing the problem, and with some help from our colleagues in the university museum world we will hopefully together be able to find solutions in the future.

Anne O'Tate: A tool to support user-driven summarization, drill-down and browsing of PubMed search results

Background

PubMed is designed to provide rapid, comprehensive retrieval of papers that discuss a given topic. However, because PubMed does not organize the search output further, it is difficult for users to grasp an overview of the retrieved literature according to non-topical dimensions, to drill-down to find individual articles relevant to a particular individual's need, or to browse the collection.

Results

In this paper, we present Anne O'Tate, a web-based tool that processes articles retrieved from PubMed and displays multiple aspects of the articles to the user, according to pre-defined categories such as the "most important" words found in titles or abstracts; topics; journals; authors; publication years; and affiliations. Clicking on a given item opens a new window that displays all papers that contain that item. One can navigate by drilling down through the categories progressively, e.g., one can first restrict the articles according to author name and then restrict that subset by affiliation. Alternatively, one can expand small sets of articles to display the most closely related articles. We also implemented a novel cluster-by-topic method that generates a concise set of topics covering most of the retrieved articles.

Conclusion

Anne O'Tate is an integrated, generic tool for summarization, drill-down and browsing of PubMed search results that accommodates a wide range of biomedical users and needs. It can be accessed at [4]. Peer review and editorial matters for this article were handled by Aaron Cohen.

1. Background

Anne O'Tate was developed as a part of the Arrowsmith project [1-4], which has been developing informatics tools for advanced text mining of the biomedical literature. We sought to create a tool for carrying out PubMed searches [5] that did not require the user to progressively reformulate the initial query; that would assist the user in finding the most relevant articles quickly and efficiently; and that would summarize the salient features of a given set of articles – e.g., given a set of articles discussing gene X, to give a list of diseases that gene X has been studied in, or given a set of articles on disease Y, to give a list of symptoms that have been described in that disease. The present paper describes the current implementation of Anne O'Tate, which is used routinely by our group for conducting PubMed searches. The tool has been placed on the Arrowsmith homepage [4] as a free, public web-based service.

2. Implementation

2.1 Query interface

The PubMed query interface [5] was imported into the Anne O'Tate web page, so that when a user types in a query, it is sent to PubMed using the NCBI E-Utilities (ESearch and EFetch) [6] to obtain the PubMed IDs, and thereby takes advantage of the pre-processing that occurs within PubMed. Given the set of PubMed IDs, articles are looked up in a local MEDLINE/PubMed database; for articles not included in the local database, E-Utilities are used to download the records of those (generally very recent) articles. There is no restriction on the number of articles retrieved from PubMed and displayed initially to the user. However, to limit the computational load on the system, a limit was placed on the number of papers that are processed further (as discussed below). At present, the default limit is set to process further only the 25,000 most recent articles of a given query.

2.2 MEDLINE term database

A database of terms was created including all of the words and phrases [n-grams (n = 1,2,3)] that occur in the title of at least one article in MEDLINE. A simple tokenizer (to remove sentence delimiters and change the text to lower case) and a stemmer (to handle plurals) have been applied [7]. In total, 15.5 million terms were extracted. Document frequency is defined as the number of different articles in MEDLINE that contain the term in either title or abstract. Each term in an article is counted only once, even though it may occur several times in that article. We intend to update the term database yearly.

Semantic categories

Terms were run through the NIH MetaMap program (MMTx version 2.0) [8] to assign each term to one or more semantic categories, if possible, as defined by the Unified Medical Language System (UMLS). The 134 semantic categories were grouped into ~15 super-categories as outlined in [9]. (For example, a number of individual semantic categories such as Hazardous or Poisonous Substance, Hormone, and Immunologic Factor were subsumed under the super-category of Chemicals & Drugs.) Because MetaMap cannot optimally recognize terms out of context, and because at the time certain terms were poorly represented in the UMLS, including neuroanatomical terms and gene/protein names, the NeuroNames vocabulary [10] and a list of predicted gene and protein names extracted from Entrez Gene [11] were added as complementary semantic categories. Anne O'Tate allows users to restrict important words (see below) or MeSH terms to any of the 15 super-categories or to any of the individual semantic categories therein; alternatively, they can retain all terms that mapped to at least one semantic category while discarding terms that failed to map at all.

2.3 Anne O'Tate categories

1. Important words

Important words distinguish a specific literature L from the rest of MEDLINE. Important words of a literature should occur significantly more frequently within the literature than overall in MEDLINE. That is, they should show high enrichment, forming a literature-specific vocabulary that is similar to the concept of a domain sub-language [12]. At the same time, important words should ideally occur in a high proportion of the articles in literature L (i.e., should have high coverage).
To create a list of words that are highly enriched within a given retrieved literature L relative to MEDLINE as a whole, the null hypothesis is that L and a given word t are independent of each other, in which case the number of articles within that literature that contain the word will follow the hyper-geometric distribution. Words occurring one time in L were discarded from consideration. Given n, the number of articles in MEDLINE containing word t in title or abstract; and N, the number of articles in MEDLINE, we calculated the parameter Ent. This parameter is related to the probability that word t occurs at or above the observed document frequency (f) in L. Specifically, the Ent score is equal to the t-statistic; for example, Ent = 3 is equivalent to the statement that t is significantly enriched in L at p = 0.001). When N is large compared to |L|, Ent is approximately:

Recent Progress and Challenges in Nanotechnology for Biomedical Applications: An Insight into the Analysis of Neurotransmitters

Nanotechnology offers exciting opportunities and unprecedented compatibilities in manipulating chemical and biological materials at the atomic or molecular scale for the development of novel functional materials with enhanced capabilities. It plays a central role in the recent technological advances in biomedical technology, especially in the areas of disease diagnosis, drug design and drug delivery. In this review, we present the recent trend and challenges in the development of nanomaterials for biomedical applications with a special emphasis on the analysis of neurotransmitters. Neurotransmitters are the chemical messengers which transform information and signals all over the body. They play prime role in functioning of the central nervous system (CNS) and governs most of the metabolic functions including movement, pleasure, pain, mood, emotion, thinking, digestion, sleep, addiction, fear, anxiety and depression. Thus, development of high-performance and user-friendly analytical methods for ultra-sensitive detection of neurotransmitters remain a major challenge in modern biomedical analysis. Nanostructured materials are emerging as a powerful mean for diagnosis of CNS disorders because of their unique optical, size and surface characteristics. This review provides a brief outline on the basic concepts and recent advancements of nanotechnology for biomedical applications, especially in the analysis of neurotransmitters. A brief introduction to the nanomaterials, bionanotechnology and neurotransmitters is also included along with discussions on most of the patents published in these areas.

Haematology

Haematology is the long-awaited, revised and updated version of the original edition first published in 1999 as part of the highly respected 'Biomedical Sciences Explained' series. This time we have a new editor as Chris Pallister has been joined by Malcolm Watson, and the book has grown by over 130 pages. Initial impression is of a very nicely presented text with a clear, uniform style throughout and numerous boxes containing mainly historical and some explanatory annotations, which add a nice touch. All illustrations are greyscale but they work well.
All of the major headings that one would expect in a book of this kind are represented, with 20 chapters in total, starting with an initial introduction to blood and haemopoiesis, followed by substantial chapters covering red cells, a chapter covering non-malignant leucocyte disorders, seven chapters covering all major areas of haematological malignancy, and finally three chapters devoted to coagulation. Each chapter begins with clearly stated learning objectives.
Chapter 3 introduces us to the concepts of anaemia and the description of red cells. On page 43 we are told that the term 'hyperchromic' is not used, but in practice it sometimes is - spherocytes do lose their area of central pallor because they are no longer biconcave, but they are often smaller than normal red cells and have an increased haemoglobin concentration, and they do look darker upon microscopic examination. Even the suggested further reading (Bain) supports careful use of this term.
Chapter 4 provides sound coverage of the disorders of iron metabolism and the relationship between hepcidin and ferroportin that would not have been found in any book published in 1999.

Automatic skin tumour border detection for digital dermoscopy using a new digital image analysis scheme

Malignant melanoma and basal cell carcinoma are common skin tumours. For skin lesion classification it is necessary to determine and calculate different attributes such as exact location, size, shape and appearance. It has been noted that illumination, dermoscopic gel and features such as blood vessels, hair and skin lines can affect border detection. Thus, there is a need for approaches that minimise the effect of such features. This study aims to detect multiple borders from dermoscopy with increased sensitivity and specificity for the detection of early melanoma and other pigment lesions. An automated border detection method based on minimising geodesic active contour energy and incorporating homomorphic, median and anisotropic diffusion (AD) filtering, as well as top-hat watershed transformation is used. Extensive experiments on various skin lesions were conducted on real dermoscopic images and proved to enhance accurate border detection and improve the segmentation result by reducing the error rate from 12.42% to 7.23%. The results have validated the integrated enhancement of numerous lesion border detections with the noise removal algorithm which may contribute to skin cancer classification.
KEY WORDS: Carcinoma, basal cell.
Dermoscopy.
Image processing, computer assisted.
Skin neoplasms.
Introduction
Skin cancer is one of the most common types of cancer1 among populations worldwide. Generally, skin cancer is divided into two groups, melanoma and non-melanoma. Malignant melanoma3 usually appears as an enlarged naevus with multiple shades of colours, and its border tends to be irregular and asymmetric with protrusions and indentations. This is a potentially fatal malignancy3 of the epidermal melanocyte which invades the dermis of the skin, and thus early detection is vital to the treatment process.
Basal cell carcinoma' is the most common form of cancer in the United States. According to the American Cancer Society, 75% of all skin cancers are basal cell carcinomas. It develops in the epidermis and grows slowly and painlessly. A new skin growth that bleeds easily or does not heal well may suggest basal cell carcinoma. The majority of such tumours occur on areas of skin regularly exposed to sunlight or other ultraviolet (UV) radiation.

Recent advances in biomedical applications of accelerator mass spectrometry

The development of biomedical AMS

The use of radioisotopes has a long history in biomedical science. Isotopic enrichment of xenobiotics with 14C is routinely used as a method of following their metabolic fate in both animals and humans, and a drug is typically synthesized such that the natural abundance of 14C is increased from the background level of 1.2 × 10-10% to 20% or even higher depending upon the compound. The low energy β-radioactivity is then used to track the radiolabeled compound and its metabolites in biological samples derived from laboratory animal or human studies. LSC has been generally used for a long time to detect, follow and quantitate levels of radiotracer in such studies. There are occasions, however, when the low sensitivity of LSC becomes experimentally limiting, while the technique of AMS has now changed the experimental paradigm because its extremely sensitive detection limit virtually removed the previous experimental barriers.
The high sensitivity of AMS indeed affects experimental designs in several ways. First, the radioisotopic dose can be reduced to inconsequential levels of radiolysis, hazardous waste streams, and human subject exposure. Secondly, the chemical dose to a biological system, including humans of all ages and health status, is minimized to sub-physiological and sub-toxic doses. This allows a realistic analysis of the effects arising from low chemical doses. For example, children and women of child-bearing ages, who are important targets of increased health-related research, are suitable subjects at the low doses afforded by AMS [10,11], since the administration of such low levels of 14C are considered non-radioactive from a regulatory point of view. Finally, even if the sampled material needs fractionation to specific biomolecules prior to quantitation, the sample sizes are reduced to amounts that can be obtained from well-defined, and often non-invasive procedures.
For a practical AMS measurement, biological samples containing 0.2–5 mg of carbon must be converted to solid carbon (graphite or fullerene) using a two-step process [12]. In a quartz tube, and using excess copper oxide (CuO), the sample's biological carbon is oxidized to CO2. The CO2 is then reduced to solid carbon by both reduction with titanium hydride and zinc powder and catalyzation with either iron or cobalt. Because this process is independent of the chemical nature of the sample, it eliminates interference or suppression from other sample components. Therefore, AMS provides one piece of information about the sample of carbon measured: the precise 12C:14C ratio. In AMS, one measures the isotope ratio with respect to that of a well-known (external) standard in order to produce an absolute isotope concentration for the combusted sample [13,14]. With AMS, experimenters only need the fractional elemental abundance of the sample and the specific activity of the tracer compound in order to obtain, in the units most useful for interpretation, the concentration of the tracer in the sampled material. The mechanics of an AMS instrument, the mathematical conversions of the measured values to meaningful "Modern" values, and the comparisons with LSC are well reviewed in the literature [3,11,15-17].
For the first time in 1990, sensitive and precise quantitation of 14C was applied to the analysis of biological samples containing enriched 14C-labeled carcinogens for toxicology and cancer studies by Turteltaub et al. [18]. Their research quantified chemical binding of the 14C-labeled carcinogens to DNA at the level of 1 binding in 1011 bases. The benefits of using AMS for the analysis of samples derived from radiotracer studies with humans soon became apparent, since AMS produces very specific quantitation with simple analysis [19]. Any isotope concentration greater than the known stable natural 14C background must arise from an introduced isotope label ("introduced" includes contamination, which must be carefully controlled and avoided). In the simplest experimental design, there is only one external radioactive source, perhaps a radiolabeled compound introduced into the biological system at a specific time. The isotope ratio of the isolated sample is then easily converted to the concentration of the labeled compound and its metabolites per g or ml of the analyte.
Not surprisingly, AMS has soon become a tool of choice for pharmacokinetic analyses [10,11,16]. All the metabolites of the compound that contain the labeled moiety can be directly quantified in chromatographic separations without resorting either to secondary standards or to prior knowledge of metabolic pathways. Although some fluorescent methods quantitate into the amol levels [20,21], they require derivatization procedures that are not suitable for in vivo tracing, create tracers that are not chemically equivalent, and are less general in applicability across many biological systems. Conversely, AMS is specific only to the labeled compound in any chemical or biological medium. Such specificity requires neither prior speciation nor the introduction of either molecular modifications or internal standards. With AMS, it is possible to conduct radiotracer studies in human with the administration of such low levels of 14C [10,11].
The most recent innovation using AMS technology is the so-called "microdosing" concept [10]. Choosing a drug for clinical trials from numerous candidates is very much a hit-and-miss business. Data are gathered from in vitro, in vivo, and in silico models in order to predict the drug's behavior in humans but such methods are probably only about 60% predictive. Presented with a choice of good candidates, it would be better to take them all into human subjects. This would, however, be prohibitively expensive, as each compound would require a significant package of toxicological safety testing. Alternatively, each candidate drug could be given to human volunteers at very low levels of a few tens, or at most a hundred μg. At these levels, only a limited toxicology package is required and in vivo human data can be acquired for candidate selection [22]. Only AMS has the required sensitivity to conduct such studies at the low μg level.
In this review, the recent development of AMS methods to the present day in biomedical/bioanalytical research where it is being strategically used with high precision (see Figure 2 for the major applications of AMS discussed here) will be followed.

A structural constitutive model considering angular dispersion and waviness of collagen fibres of rabbit facial veins

Constitutive modelling of vascular tissue has been a challenging area for several decades [1,2]. Structural constitutive models, in particular, attempt to integrate information on composition and structural arrangements of tissue to avoid ambiguities in material characterization. In this way, they offer an insight into the function, structure and mechanics of the principal wall components i.e. elastin, collagen and vascular smooth muscle cells. Structural constitutive models have been developed for a variety of tissues and tissue components including blood vessels [3-8], skin [9], pericardium [10], heart valves [11], tendons and ligaments [12], articular cartilage [13].
In blood vessels, collagen fibres appear in coiled and wavy bundles in their unloaded state [14,15] and the individual collagen fibres have a deviation from their mean orientations [16,17]. In the media, collagen fibres are strongly co-aligned [17]. Canham et al. [18] reported the angular standard deviation of fibres in the media as 5.2° in brain arteries and 5.6° in coronary arteries [18]. However, within the adventitia layer, collagen fibres have large angular dispersion [17]. A complete structural constitutive model for vascular collagen should incorporate both waviness and orientational distribution of fibres.
Perhaps the most complete framework for structural modelling of fibrous tissue has been presented by Lanir et al. [19-21]. In this framework, the total strain energy function (SEF) is assumed to be a result of the collective contribution of the individual fibres linked with tensor transformations from the fibre coordinates to the global tissue coordinates. A number of previous studies have followed this approach and have incorporated waviness [22,23] or orientational distribution of collagen fibres [10,11,24], to study the effects of collagen micro-organization on the macroscopic behaviour of vascular tissue. Other studies have followed a different approach and involved the use of invariants [22,23,25]. Yet, to the best of our knowledge, currently, there is no structure-based SEF for the vascular wall, which includes both waviness and angular distribution of collagen fibres and which has been verified using standard inflation-extension tests. We have therefore set as goals of this study to, first, extend our previously developed model [22,23] to include both waviness and angular distribution of collagen fibres, second, to perform a parametric study to analyze the effects of orientational distribution parameters on the macro-mechanical behaviour of the vascular tissue and, third, to assess the suitability and importance of including fibres' orientational distribution by applying the model to experimental data from inflation-extension tests.

Dispensing pico to nanolitre of a natural hydrogel by laser-assisted bioprinting

Bioprinting techniques are emerging as potential instruments for the multidisciplinary field of tissue engineering and regenerative medicine. The possibility to arrange multiple cell types in a computer-controlled 3 D manner may substantially improve our understanding about complex cell-cell and cell-environment interaction. Among all bioprinting techniques [1-3], laser-assisted bioprinting (LaBP) approaches based on laser-induced forward transfer were demonstrated to possess additional benefits: (i) tiny amounts of different hydrogels with a wide range of rheological characteristics can be printed in a controlled and precise way [4-8], which is important for the realisation of 3 D cell-hydrogel constructs mimicking various stiffnesses of native tissues; (ii) any desired cell amount ranging from single [9] to dozens of cells [10] can be printed without observable damage to pheno- and genotype [7,9-12]; and (iii) the printing speed (number of droplets per second) depends mainly on the pulse repetition rate of the applied laser. Printing speed of 5000 droplets per second was recently demonstrated [4], which enables fast generation of large cell constructs.
Already demonstrated biological applications reflect the flexibility of this laser printing technique, for instance: (1) generation and differentiation of 3 D stem cell grafts [13], which can be used as in vitro tissue models for the screening of drug effects; (2) assembly of cellular micro arrays of single [11] and multiple [14] cell types for systematic studies of fundamental aspects of cell-cell and cell-environment interaction; (3) computer-controlled seeding of 3 D scaffolds with multiple cell types [15]; and (4) in vivo bioprinting of nano-hydroxyapatite [16]. The principal laser-assisted bioprinting setup (see Figure 1) consists of a pulsed laser source and two positioning systems on which a donor-slide coated with an energy-absorbing material layer carrying the cell-hydrogel compound, and a collector-slide receiving the printed biological material are located. In brief, laser pulses are focussed through the donor-slide onto the gold layer which is evaporated locally at the focal point. This rapid energy deposition leads to the generation of a jet dynamic [17] resulting in the deposition of a tiny hydrogel volume on the collector-slide. Control of the printed volume is a key issue and great efforts have been made to understand the relationship between the printed volume and the processing parameters [5,6,8,18]. Providing a deeper understanding of this relationship is crucial in order to make the printed volume with embedded cells more predictable, and to enable theoretical simulation of cell-cell interaction, cell-extracellular matrix interaction and signalling pathways [12]. However, the whole jet generation process is not completely understood. Moreover, recent studies mainly used glycerol-based fluids to investigate the effects of the laser fluence and fluid properties on the droplet volume [5,8,18] instead of fluids based on fibrin-precursors, which are widely used for bioprinting of different cell types

Recent developments in biomedical optics


The rapid growth in laser and photonic technology has resulted in new tools being proposed and developed for use in the medical and biological sciences. Specifically, a discipline known as biomedical optics has emerged which is providing a broad variety of optical techniques and instruments for diagnostic, therapeutic and basic science applications. New laser sources, detectors and measurement techniques are yielding powerful new methods for the study of diseases on all scales, from single molecules, to specific tissues and whole organs. For example, novel laser microscopes permit spectroscopic and force measurements to be performed on single protein molecules; new optical devices provide information on molecular dynamics and structure to perform `optical biopsy' non-invasively and almost instantaneously; and optical coherence tomography and diffuse optical tomography allow visualization of specific tissues and organs. Using genetic promoters to derive luciferase expression, bioluminescence methods can generate molecular light switches, which serve as functional indicator lights reporting cellular conditions and responses in living animals. This technique could allow rapid assessment of and response to the effects of anti-tumour drugs, antibiotics, or antiviral drugs. This issue of Physics in Medicine and Biology highlights recent research in biomedical optics, and is based on invited contributions to the International Conference on Advanced Laser Technology (Focused on Biomedical Optics) held at Cranfield University at Silsoe on 19--23 September 2003. This meeting included sessions devoted to: diffuse optical imaging and spectroscopy; optical coherence tomography and coherent domain techniques; optical sensing and applications in life science; microscopic, spectroscopic and opto-acoustic imaging; therapeutic and diagnostic applications; and laser interaction with organic and inorganic materials. Twenty-one papers are included in this special issue. The first paper gives an overview on the current status of scanning laser ophthalmoscopy and its role in bioscience and medicine, while the second paper describes the current problems in tissue engineering and the potential role for optical coherence tomography. The following seven papers present and discuss latest developments in infrared spectroscopy and diffuse optical tomography for medical diagnostics. Eight further papers report recent advances in optical coherence tomography, covering new and evolving methods and instrumentation, theoretical and numerical modelling, and its clinical applications. The remaining papers cover miscellaneous topics in biomedical optics, including new developments in opto-acoustic imaging techniques, laser speckle imaging of blood flow in microcirculations, and potential of hollow-core photonic-crystal fibres for laser dentistry. We thank all the authors for their valuable contributions and their prompt responses to reviewers' comments. We are also very grateful to the reviewers for their hard work and their considerable efforts to meet tight deadlines.