Showing posts with label research. Show all posts
Showing posts with label research. Show all posts

Monday, November 10, 2014

To dream the impossible dream (Musings on TM research)

As always, stay tuned for updates

November's blog is based on an abstract from AABB's 2014 meeting in Transfusion. I always read 'Education and Training' abstracts (one of the smaller sections - go figure!), and this one caught my eye:
  • A14-030D: Chargé SB, Walsh GM. Bridging the gap: knowledge mobilization and transfusion medicine research. Transfusion 2014 Sept;54(2S):231A. 
The authors are from CBS's Centre for Innovation. 'Leading edge' on the Centre's website grates but at least it isn't 'bleeding edge.' As soon as I read 'knowledge mobilization' in the abstract I thought, 
  • 'OMG, not more management bafflegab by Canada's national blood supplier!' 
  • If there's a new buzzword out there like knowledge mobilization, you can bet CBS management will jump on it. 
That said, reading the abstract, I lost my skepticism, well at least some of it. The project to educate front-line CBS staff about the organization's research initiatives and research team is admirable.

The blog's title derives from the principal song of the musical 'Man of la Mancha' based on Cervantes' 17th C classic, Don Quixote. I hope that transfusion professionals the world over can relate to the blog's musings on the nature of research.
ABSTRACT 
Here's my version of the CBS research initiative. (Read full abstract for more details) 

Title: Bridging the gap: knowledge mobilization and transfusion medicine research
Why do it?  To transfer knowledge generated by basic and clinical research to those whose work it may affect. Unfortunately, journal publications and conference presentations have limited access.
What did they do? CBC developed these tools:
  • Summaries in plain language of notable publications were published online monthly and aimed at all stakeholders, including donors.
  • Knowledge to Munch On: Internal follow-up to major conferences, inc. 
    • Displays of conference posters
    • Distributing an electronic conference report
    • Lunch and Learn national webinars highlighting conference presentations. 
What did they find? Summaries in plain language: Between March 2013 and March 2014, 10 Research Units were online and downloaded >1100 times.

Knowledge to Munch On:
  • 66 conference presentations were available to staff who couldn't attend conferences
  • 3 electronic conference reports were downloaded 747 times in the 3 months after publication
  • Lunch and Learn: 8 presentations were attended by 263 staff.
    •  96% agreed with, 'This event enhanced my knowledge.' 
    •  76%felt that the knowledge was applicable to their practice.
What did they conclude? The programs' impacts are measurable and need more developing and monitoring to achieve a greater impact.

My take on the CBS research project
  1. Demographics: Who viewed the posters, downloaded the summaries and reports, attended and participated (geographical locale and health profession)?
  2. When were various components of the program available and accessed? During the work day vs lunch hours, coffee breaks, and after hours at home?
  3. Plain language summaries of 10 research units downloaded a total of  >1100 times over a year is NOT very much. 
  4. Was a Likert 5-point scale used to assess participant feedback? e.g., 96% agreed with, 'This event enhanced my knowledge' and '76% felt that the knowledge was applicable to their practice.'
Seems like a good start. Wonder how much time, effort, funds were spent and how committed CBS is to maintain the project, given the organization's overpowering emphasis on cost cutbacks, even related to its core business lines.

MUSINGS on RESEARCH
1. Research means being incurably curious about the world. Researchers, especially those involved in basic research, conduct many experiments year after year with failure after failure and little hope of success, until it happens, if it does. 

2. How many researcher dudes have you even heard of (and they are mainly dudes)? You may recognize the names of the luminaries who publish in leading journals and present often at conferences. 

But if you are a front-line transfusion professional, whether lab technologist /biomedical scientist, nurse or physician, you likely do not read papers or attend sessions on basic research, whose titles are often indecipherable. Even applied research gets little readership unless it directly affects us.

3. Many types of research exist. See this primer on medical research. On a simplistic level
  • Basic research is wondering if inherited traits might make different groups of people more or less susceptible to the same disease.
  • Applied research is trying to develop a screening test for HIV once we know it causes AIDS, and possibly making mega-bucks in the process.
4. It's easy for people to slag researchers as egg heads divorced from reality. These guys and gals get to attend conferences and seemingly live a charmed, stress-free life compared to those in the trenches. 

Indeed, I live in a university city where some politicians have long dissed academics as not living in the 'real world'. Anti-intellectualism is popular among populist politicians and a sure vote winner with some.

5. What the public does not see is the stress of researchers: 
  • Proving their worth annually by winning scarce research funds
  • Keeping spirits up in the face of experiments extending for years 
  • Defending criticism from peers when they publish findings
  • Facing condescension by some who perceive them as pampered 'ivory tower' dwellers.
6. Basic research, often derided, has a record of producing major scientific findings. One example:
Hepatitis BApplied research is all the rage among politicians these days, but basic research rivals it via serendipity. 
Hepatitis B kills more than 700,000 people annually. Prevalence is highest in sub-Saharan Africa and East Asia, where most people become infected during childhood and 5-10% of adults are chronically infected. Vertical transmission from mother to child is common. About half of all cases of hepatocellular carcinoma are attributed to chronic HBV infection.  
Today all blood donations are screened for HBV thanks to its discovery by Dr. Baruch S. Blumberg . 
In 1976, Dr. Blumberg won the Nobel Prize for Physiology and Medicine for his discovery of the hepatitis B virus. He and his colleagues discovered the virus in 1967. 
But Blumberg began as a medical anthropologist interested in the genetics of disease susceptibility. He wondered if inherited traits might make different groups of people more or less susceptible to the same disease. The research had nil to do with hepatitis.
His research involved using antibodies from multi-transfused hemophiliac patients to test blood samples collected around the world. When an antibody from a New York hemophiliac reacted with an antigen in the blood of an Australian aborigine, they called it the 'Australia antigen', and the serendipitous path to a life-saving discovery was made. 
The Au antigen was subsequently found in the serum of many multi-transfused leukemia patients. Was it related to causing leukemia? Then Blumberg's laboratory technologist developed hepatitis B. And ultimately it became clear that the Australian antigen was the hepatitis B surface antigen. 
Soon a lab test was developed to screen blood donors and a vaccine was developed.
BOTTOM LINES
  • Basic research, with unknown outcomes, often trumps applied research, despite applied research being the flavour of the decade. 
  • A researcher's life is not all roses. Far from it. 
  • All health professions should get to know each other better, including the researchers who work behind the scenes and whose work can affect us all.
FOR FUN
The blog's title derives from the musical, Man of La Mancha, based on Cervantes' Don Quixote, and its song, 'To dream the impossible dream'. 

Like Don Quixote, researchers are sometimes seen as impractical, naive, idealist dreamers. Researchers dream the dream daily. It keeps them going. They never know when something momentous will be discovered, something to improve the lives of people, like Blumberg's Australian antigen did.
As always, comments are most welcome.
FURTHER READING
  • Baruch S. Blumberg
Posted by Blut at 4:33 PM 1 comments
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Wednesday, March 16, 2011

Cultivate, convert, and cloak 'em - Sweet dreams? (Musings on chasing the 'holy grails' of blood transfusion)

Recent research papers posted to TraQ stimulated this blog. It's a 'quick and dirty' look at current research into how to make blood, and by extension blood transfusion, safer. The title derives from the research processes involved and a favorite song of mine co-written by Annie Lennox and originally released by the Eurythmics in 1983.

For years researchers have tried to find the 'holy grail' of blood transfusion in the form of the ideal oxygen-carrying red cell substitute, a search that has eluded them to date.
Although blood substitute research continues, currently many other research pathways are being explored.

Not included in this blog is an early research pathway - chop 'em - whereby enzymes chop off A and B antigens and convert all red cells to group O cells. So far research has not led to practical use. Also see this paper from 21 years ago:

CULTIVATE 'EM
Scientists in many countries are working on developing synthetic blood from embryonic stem cells but Scotland has embarked on a project to produce blood on an industrial scale.

In 2009 the Scottish National Blood Transfusion Service in collaboration with several universities began a trial to provide an unlimited supply of group O Rh negative red cells for emergency transfusions. The project has just received a further injection of funds.

Research will require cross-disciplinary teams involving medicine, bioprocess technology, and engineering.
CONVERT 'EM

Researchers in Hamilton, Ontario, Canada demonstrated the ability to generate hematopoietic progenitor and mature blood cells directly from human skin fibroblasts. News reports:
Research paper:

Converted skin cells were able to produce red cells, white cells, and platelets.

The McMaster team will also investigate converting excess, unwanted fat cells into blood using the same method. Can't you just see it?

CLOAK 'EM
Researchers in Montreal, Quebec, Canada investigated a novel way to develop a 'universal' red blood cell that involves encasing individual red blood cells within a shell formed from a biocompatible polymer. News items:
Research paper:

The polymer hides A, B, and D antigens from their respective antibodies and acts as a chemical cloaking device by masking rbc surface antigens that would otherwise trigger an immune response. The red cells still function because oxygen can penetrate the shell, allowing the rbc to supply oxygen to body tissues and organs. Patients with encapsulated rbc would eventually produce their own red cells to replace camouflaged cells, which would ultimately be broken down and excreted.

The immunocamouflage' mimics a 'find me if you can' scenario seen many times in nature.

SUMMARY

A common thread of these research initiatives is the need for interdisciplinary teams, yet another reason to break down the silos that professionals live in.

All projects are in the early stages, at least 5-10 years from being implemented in the real world. Only time will tell if they go the way of the elusive blood substitute or come to fruition and make transfusion safer.
Comments are most welcome BUT, due to excessive spam, please e-mail me personally or use the address in the newsletter notice. 
Posted by Blut at 6:55 PM 0 comments
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Sunday, June 08, 2008

What's it all about, Alfie?

This month's blog is about how we spend our time in the context of transfusion medicine research. The title comes from the song What’s it all about Alfie? and the movie of the same name starring Michael Caine (and a later version with Jude Law). Perhaps you have pondered the meaning of this oldie-goldie from the 60s?

It's a cliche to say that to get the right answers you must ask the right questions, which is the researcher's equivalent of the techno-geek's GIGO.

But even more important is to know what questions of all the questions that could be asked are worthwhile spending time trying to answer. I would not call myself a researcher, although I have done applied research, but will not let that stop me from commenting or spouting off.

Two articles caught my attention in recent issues of Transfusion and Vox Sanguinis, both out of personal historical interest.

The first paper by a College of American Pathologists committee concerns blood bank serology, something at risk of becoming obsolete but nonetheless dear to my heart.

1. AuBuchon JP, de Wildt-Eggen J, Dumont LJ for the Biomedical Excellence for Safer Transfusion Collaborative and the Transfusion Medicine Resource Committee of the College of American Pathologists. Reducing the variation in performance of antibody titrations. Vox Sang 2008 Jul;95 (1):57–65.

Summary: Because antibody titration is difficult to standardize, the CAP proficiency testing program decided to investigate whether a detailed, uniform titration procedure would reduce variation in both tube-based and gel card titres (see abstract for details). Based on results from 35 laboratories, the U.S. authors concluded that a uniform method for antibody titration at 37°C and read at the antiglobulin phase in a tube-based method with a w+ end-point (compared to a 1+ end-point) reduced inter-laboratory variability.

Related reading:
MUSINGS
Titrations - a blast from the past! Long ago I performed many a titration while working in Winnipeg with Dr. John Bowman - titrations on the plasma of women with anti-D who were candidates for intrauterine transfusion and on the plasma of women whose potent anti-D was used to manufacture Rh immune globulin.

One thing I know from working in a lab that used titrations as an adjunct to assess hemolytic disease of the newborn due to anti-D is that titre is an unreliable indicator of disease severity. Historically, it was used as a poor tool to assess whether invasive procedures such as amniocentesis and later PUBS were warranted.

Depending on the method, the red cell phenotype used, and operator technique, titres can vary significantly. Technically that's a 2-tube difference (or more) in a titration that uses a doubling dilution, e.g., titres of 4 and 8 are not considered significant but those of 4 and 16 would be.

While an anti-D (or anti-K) with a high titre (however that is defined) can alert us to the need to monitor current and future pregnancies, can getting more consistent inter-laboratory endpoints significantly influence clinical management?

Obtaining more reliable titres among labs is a good thing, but how important is it practically and clinically?

A second paper that makes the point:

2. Seltsam A, Agaylan A, Grueger D, Meyer O, Blasczyk R, Salama A. Rapid detection of JMH antibodies with recombinant Sema7A (CD108) protein and the particle gel immunoassay. Transfusion 2008 Jun;48(6):1151–5.

Summary: The German authors describe a method to detect anti-JMH with particles coated with recombinant semaphorin 7A, the protein that carries the JMH blood group antigens, presumably thus making identification of anti-JMH possible without having rare JMH-negative red cells.

MUSINGS
Another blast from the past - John Milton Hagen. Was there a patient by this name like Mrs. Kellacher whose ani-K led to the discovery of the antiglobulin test by Coombs? I've forgotten.

Anti-JMH was once considered a high-titer, low-avidity (HTLA) antibody, now an outdated term. The phenomenon is caused by the low number of antigen sites on red cells, not by antibody avidity, and not all antibodies classified as HTLA have a high titre.

JMH antibodies are usually harmless, although they can cause serologists problems by hiding clinically significant antibodies, since they react with most red cells. Rare cases of people with a variant JMH phenotype producing a clinically significant alloantibody have been reported.

While it would be useful to be able to identify anti-JMH without having rare JMH-negative red cells, how important is it practically and clinically?

Related reading

BOTTOM LINE
Granted that these articles are cherry picked to serve a point, they do illustrate that sometimes research, even applied research, may have questionable technical or clinical relevance.
By happenstance, the June issue of Transfusion features the status of transfusion medicine in developing countries. Particularly noteworthy is this review paper:
The paper's conclusion begins by noting, Blood safety remains an issue of concern in Africa and especially in countries of Sub-Saharan Africa where the key factor to most transfusion-related problems is the lack of financial resources.
It ends with these words: .... this is one of the unfortunate paradoxes of the history of humanity: it is those regions most in need of the means to fight prevalent diseases that have least access to them.

Yet we in developed counties continue to spend resources on ways to improve titration reliability and identification of antibodies such as anti-JMH. Those who do such investigations are respected researchers who have devoted their professional lives to improving transfusion medicine. But how important are some of these initiatives in the grand scheme of things?

An earlier blog discussed this issue of the discrepancy between them and us:
The next time you read an article in a scientific journal - or if you are a researcher who is contemplating spending your valuable time and finite resources on investigating a problem, and you can choose from issues A, B, or C - I encourage you to ask, What's it all about Alfie?
The opening lyrics:
What's it all about, Alfie?
Is it just for the moment we live?
What's it all about when you sort it out, Alfie?
Are we meant to take more than we give.....
ADDENDUM- The nature of research

Unfortunately, research is often many tedious rounds of slogging it out with nothing working - until it does - should that happen. It may not. You cannot predict the result.

We can also differentiate between basic ("pure") research and applied research.

Pure research, as historically done at universities, is typically driven by the curiosity of the researcher with no practical application in mind. The reason is to create new knowledge by following the researcher's interests and passions. Although sometimes denigrated as a waste of time and money by anti-intellectuals, basic research has often resulted in incredible, if unforeseen, benefits to mankind. For a fun peek into the lives of researchers see
Applied research, becoming predominant at universities (which some would argue is unfortunate) is more focused on solving particular problems. For example, medical research is typically applied research and compares various treatments or drugs to investigate which gives better patient outcomes. In a prospective experimental study, the researcher creates a null hypothesis (treatment A and treatment B are the same and will result in similar patient outcomes) and tests it by conducting experiments.

SERENDIPITY
Often, research, regardless of its original purpose, results in unexpected, happy outcomes. For example, in the 1960s Baruch Blumberg was a geneticist (not a virologist) who was studying the genetic variation of proteins in blood. He and his colleagues decided to test the hypothesis that patients who received many transfusions might develop antibodies against polymorphic serum proteins which they had not inherited, but which the blood donors had.

Using double diffusion in agar gel they did find sera in multi-transfused patients that contained precipitating antibodies and in 1963 unexpectedly hit magic. When testing the sera of American hemophilia patients against that of an Australian aborigine, they found a precipitin band unlike any others and called it the Australia antigen.

Eventually, the Australia antigen was shown to be the HBsAg. In the process, one of Blumberg's technologist contacted hepatitis B. From this serendipitous discovery came tests for HBV infection and a vaccine. For the entire fascinating story, see
Unfortunately, HBV infection remains one of mankind's major diseases and killers.

Summary: Blumberg did not know if he would find antibodies in transfused patients stimulated by serum proteins in donor blood. Most particularly, he did not know that one of those proteins would be the hepatitis B surface antigen. And when he found it, no one knew what it was. My favorite quote about research is by Carl Sagan:
  • “Somewhere, something incredible is waiting to be known.”
Posted by Blut at 5:32 PM 1 comments
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