Silly Sunday #42 Open Access Week around the Globe

23 10 2011

Open Access logo and text

Open Access Week, a global event now entering its 5th year, “is an opportunity for the academic and research community to continue to learn about the potential benefits of Open Access, to share what they’ve learned with colleagues, and to help inspire wider participation in helping to make Open Access (OA) a new norm in scholarship and research”.

It takes place from October 24 to 30 in many places around the globe.

Benjamin Hennig, whose PhD research was built on the work of the Worldmapper project (see earlier post here) created and updated a map of this year’s OA- activities together with SPARC (Scholarly Publishing and Academic Resources Coalition), who are the organisers of the event.
It is a positive trend that India and parts of Africa have many OA-activities next week. (they are relatively large on the map, especially when compared to proportion of scientific papers produced in the world, as shown on Worldmapper).

For further information see the blog post of Benjamin Hennig at his blog: Views of the Worlds.

You can follow Worldmapper at Facebook.





Complementary Medicine & Pharmacists

30 11 2009

I don’t know if the situation is the same in other countries, but in the Netherlands we can only get prescribed medications in pharmacies. Drugstores are only allowed to sell over-the counter (OTC) medicines.

Most Pharmacies have a small shop of 5 square meters (besides a large storage room). What surprises me is that the counter is not only full with non-allergic creams, and the shelves are not only filled with liquorice and plasters, but the counter and shelves predominantly display naturopathic and herbal “medicines”. In this flu-season there are even leaflets how to prevent flu with all kinds of naturopathic medicine. Dr Vogel’s Echinaforce “helps to augment your natural resistance, lowers the risk of flu and shortens the duration or decreases the severity of symptoms once you have the flu” (..”vermindert u de kans op griep en herstelt u sneller als u toch ziek wordt“). Apparently A Vogel.nl (via Biohorma) started a campaign in the Netherlands. At their website there is even an advertisement for an offer by an insurance company -OHRA- because it generously refunds homeopathic medicine. Biohorma also made a You-Tube video.
In contrast, in the US there is a disclaimer at the Echinaforce site:” These statements have not been evaluated by the Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure or prevent any disease.”

There is no evidence that Echinacea prevents flu (see Cochrane Review and de Volkskrant [Dutch newspaper referring to clinical trials]), although it is not excluded that it helps for the early treatment of colds in adults.

Isn’t such a promotion of ineffective stuff a bad advice considering we have  a real flu-epidemic, and given the inverse relationship between pediatric vaccination and CAM usage (see Respectful Insolence)?

It is quite confusing, however, because Echinacea is advertised as an homeopathic medicine, whereas it seems a herbal medicine (not diluted ad infinitum). To date there is no evidence that homeopathy ‘works’. All 6 published Cochrane systematic reviews with ‘homeopathy’ or ‘homeopathic’ in the title conclude that there is little or no evidence that it works beyond the placebo-effect.

During the recent The House of Commons Science and Technology Committee meeting calling in homeopaths and scientists to discuss evidence for the alternative therapy Prof. Dr Ernst (with experience as a homeopath) said: “I have supplied a list of systematic reviews of homeopathy. There are two dozen. None in that list were positive.” (see this excellent summary of the meeting by Ian Sample). For the entire memorandum of Dr Ernst see here.

Besides that the clinical trials are ineffective, the whole theory is incompatible with the laws of physics and chemistry.

Nevertheless:

  • There is a lot of homeopathic research going on, i.e. funded by the NHS (National Health Sevice) in the UK and the NCCAM (National Center for Complementary and Alternative Medicin, NIH) in the US.
  • In the UK homeopathic medicine is endorsed by the MHRA (Medicines and Healthcare products Regulatory Agency)
  • CAM is booming business (£1.5bn industry in the UK)
  • CAM is covered by insurance companies.
  • CAM is sold and sometimes advocated by pharmacists.

Thus all over the world people are buying these ineffective homeopathic medicines while believing they ‘work’, or at least cause no harm. However, while homeopathic medicines may not harm themselves, they may cause harm if they are used in place of proven treatment for any life-threatening illness.” Indeed the WHO has warned people with conditions such as HIV, TB and malaria not to rely on homeopathic treatments (BBC NEWS 20 August 2009

For me it is incomprehensible, that pharmacists who are trained in pharmacology and chemistry (at the University Level), just sell those ineffective costly water-dilutions and advocate them directly or indirectly by putting them on the shelves, providing ample leaflets and brochures and giving positive “advise”. What could be the reason for doing that other than ignorance or MONEY?


Recommended Reading:

Photo Credits

  1. Pharmacists mortar and pestle http://commons.wikimedia.org/wiki/File:PharmacistsMortar.svg
  2. Homeopathic Medicine on the shelves http://www.flickr.com/photos/caseywest/ / CC BY-SA 2.0
    (this photo has nothing to do with the subject)
, but all kind of complementary medicine (CAM).
Reblog this post [with Zemanta]




Martin Bril: the Author, his Death and his Cancer

23 05 2009

Martin BrilMartin Bril is dead.

No “news“, it happened a month ago: April 22.

Martin Bril was a well known Dutch writer, poet and columnist – and the man who invented “skirt day”.

He loved live -and love- in all it’s simplicity. He needed few words to describe the essence of things or as he would say: “The surface is deep enough”. But you know, it is looking at one drop of water and understanding the ocean.

Other expressions: “Good is better than bad” and “You’ve people that bang the guitar really hard for hours, but I rather hear J.J. Cale. Always finished within 4 minutes, but the music stays with you.”

I liked his stories/columns most of the time, they often made me smile.

It is always sad when somebody dies young (Martin was 49), whether a “celebrity” or not. Especially when he leaves two young children and a wife.

I didn’t expect it and it really hit me. Why? I knew he had had cancer, but I thought it had gone. So did he a few years ago. I found a video-interview with him in 2007, where he said: “soon I will be declared “cured” – but then you will see it will return the other day.” In another interview I read: You never beat cancer”, that’s Lance Armstrong-language. Cancer goes away or it stays. It often stays.

I always thought he had colon cancer, but it was esophageal cancer. That’s the trouble with Dutch:Martin Bril Donkere Dagen

  • esophagus = slokdarm,
  • jejunum, ileum = dunne darm
  • colon = dikke darm.

Notice they all have “darm” in them. Mostly colon cancer is called “darmkanker” (or “dikke darmkanker”), and because esophagus is called slokdarm, slokdarmkanker is mistaken for darmkanker, which is quite another disease with other prospects.

Stupid, journalists keep on using the wrong name. Not that it matters a lot now, but still.

More “incorrect” was the fact that I first saw the announcement of his death in a newsletter from dokterdokter.nl (below). It is an online medical information site for patients. I have been getting their newsletter for years now, because -for one thing or another- I’m unsuccessful in unsubscribing to it. Dokterdokter.nl is typically a website that gives very general information, mostly leading to the advise “to check your doctor first”.

dokterdokter Martin Bril geheel

What struck me (besides the fact that I was taken by his death) was that his death was presented as Medical News, next to an enormous “oral sex” headline and the headline “what happens if you die?”. As if it was a tabloid. The message (he died the day before):

Martin Bril finally succumbed to esophageal cancer at the age of 49. Esophageal cancer has a bad prognosis. Why?
(if you click: )

“Martin Bril, the well known author …, died of esophageal cancer at the age of 49. He was a real hedonist. Cigarettes and alcohol were part of his life. Many years he had fought cancer, but Wednesday April 22 he lost his fight. Few people really completely recover from this illness.”

(….) Generally, the disease has to do with your lifestyle. In Western Countries, smoking and excessive alcohol consumption are the most important causes of esophageal cancer.

And then it continues summarizing the brochure of the Dutch Cancer Society (KWF- kankerbestrijding)

Whereas most medical sites (including the Dutch Cancer Society, from which all the information was taken) just neutrally say that the cause is unknown, but that alcohol and smoking are known risk factors for esophageal cancer, -and even more so in combination- dokterdokter puts a direct link between Martin’s lifestyle and his death, as if it was his own fault. Maybe it was, but at that moment I didn’t want to know. It didn’t matter. I found it disrespectful, tasteless. I’m quite interested in health and medicine and mechanisms, but the reason of his death -at this moment- was less important than his death itself.

As a matter of fact, Martin stopped using liquor and cocaine in 1997 after given an ultimatum by his wife (“you have two young kids!”) and after attending a trial of a drug baron (Johan V., de Hakkelaar) (to write about). He also wanted to quit smoking. I don’t know whether he succeeded, but he helped STIVORO (“for a smokeless future”) with their campaign (2002) by writing a beautiful column and making a video about (the difficulty of) quitting smoking. “I stopped smoking, because I didn’t like it anymore. Moreover, my kids didn’t want me to die because of smoking……..”

How much better was the reaction of STIVORO to the death of Martin, saying “we have lost a talented author” and thanking him for his input. Just a short notice and ending with the column Martin had written for them: “Did you ever tried to quit smoking?…I did”.

——————73554771_f75ce49f1a rokjesdag

Bij Nederlanders hoef ik Martin Bril nauwelijks te introduceren. Dat ik hier over hem schrijf heeft vooral te maken met het stukje dat ik in de nieuwsbrief van Dokterdokter.nl las. In feite was het dit bericht, waardoor ik wist dat hij gestorven was. Voor mij een schok. Ik lees de Volkskrant niet meer, dus het was mij ontgaan dat het slecht met hem ging. Het is ook een jonge vent, jonger dan ik, met twee dochters, net als ik. Zo kom het altijd nog een beetje dichterbij. En hij kon mooi schrijven. “De oppervlakte was diep genoeg,” zo zei hij, maar het was bij hem net of je in een druppel de hele oceaan kon zien.

Voor het eerst zag ik trouwens dat hij slokdarmkanker had. De meeste journalisten spraken van darmdanker, waar men in de regel toch dikkedarmkanker mee bedoelt. Slokdarmkanker is een heel andere ziekte, met een heel andere prognose. Vreemd dat het meerendeel van de journalisten het toch steeds over darmkanker heeft

Maar dit terzijde. Ik vond het vreemd, dat het bericht als een “nieuwsaankondiging” stond naast de kop “orale sex” en “hoe voelt het als je dood gaat”. Misschien had Martin er wel om kunnen lachen, maar ik vond het bizar. Het verhaal zelf vond ik ook nogal ongepast.

Wat stond er?

De ziekte slokdarmkanker werd schrijver Martin Bril op zijn 49e fataal. Het is een ziekte met slechte vooruitzichten, mede omdat het vaak laat wordt ontdekt.

“Schrijver Martin Bril, bekend van boeken als De kleine keizer en Arbeidsvitaminen en van zijn columns in de Volkskrant, is op 49-jarige leeftijd aan slokdarmkanker overleden. Hij was een echte levensgenieter, sigaretten en alcohol waren een vast onderdeel van zijn leven. Al vele jaren streed hij tegen kanker, maar woensdag 22 april was zijn strijd gestreden. Maar weinig mensen weten volledig te herstellen van deze ziekte.”De ziekte heeft meestal te maken met de leefstijl van mensen. Roken en overmatig alcoholgebruik zijn in Westerse landen de belangrijkste oorzaken voor het ontstaan van slokdarmkanker.

Andere bronnen –ook de KWF-brochure, waar dit stuk aan ontleend is, schrijven steevast dat de oorzaak niet bekend is, maar dat roken en alcohol (vooral in combinatie) de belangrijke risicofactoren zijn. Mogelijk is zijn leefwijze inderdaad de belangrijkste reden geweest dat hij slokdarmkanker heeft gekregen. Nou en? Is het nodig om dit zo op te schrijven? Een dag na zijn dood? Ik vond het nogal oneerbiedig. Misschien dacht men bij dokterdokter.nl dat het schrikeffect mensen zou weerhouden om veel te roken en te drinken, want “kijk, daar krijg je slokdarmkanker van!!” Behalve dat dokterdokter niet bepaald het juiste publiek (de “zelfkanters” en “hedonisten”) zal bereiken, zal zo’n actie sowieso weinig zoden aan de dijk zetten. Dan was Martin’s bijdrage aan de Stivoro campagne “stoppen met roken” (2002/2003) waarschijnlijk veel effectiever. Hij schreef een column voor ze en werkte mee aan een video.

Martin zei: “Ik stopte met roken omdat ik er geen zin meer in had. Bovendien; mijn kinderen vonden dat ik er niet dood aan moest gaan”. Eerder, na een ultimatum van zijn vrouw en het bijwonen van een zitting tegen de drugsbaron de Hakkelaar, was hij al gestopt met alcohol en coke.

Zo anders was ook de reactie van Stivoro. Niets vingertje wijzen: “zie je wel!”, maar dit:

“Samen met de rest van Nederland treurt STIVORO om het heengaan van een bijzonder mens en groot schrijver: Martin Bril

STIVORO heeft Martin leren kennen toen hij zich enthousiast inzette voor onze ‘Stoppen met roken’ campagne van 2002/2003. Hij was toen bereid zijn persoonlijkheid en zijn schrijftalent voor deze campagne in te zetten.

Wij zijn dankbaar dat we met hem hebben mogen samenwerken. We wensen zijn familie en andere dierbaren heel veel sterkte toe.

Hij schreef voor ons de volgende column:

“Bent u wel eens gestopt met roken?
Ik wel……..”

Photo Credit (CC):





What I learned in 2008 (about Web 2.0)

2 02 2009

Grand Round is a weekly collection of the best writing in the medical blogosphere. The coming Grand Rounds (February 3rd, 2009), hosted by Not Totally Rad has the following theme:

February is the first anniversary of my blog. Therefore, the loose theme for submissions will be anniversary-related: write about something cool or important that you’ve learned in the past year.

Well, I have learned a lot in the past year. The most profound personal experience was the death of my father. I experienced how it is to loose a beloved, but I also learned that death and grieve can affect people so deeply that it changes their behavior. I now understand this behavior (anger, mental confusion) is a manifestation of deep grief, which is transient and natural. Luckily our body and mind appear very resilient.

I will restrict to another thing I’ve learned: Web 2.0.
Just like the “Samurai Radiologist” I started a blog in February 2008. Thus Laika’s MedLibLog also celebrates its first anniversary.

Useful Web 2.0 tools

This blog was started as a tool to communicate thoughts, new found skills and ideas with other (>150) SPOETNIK course members, Spoetnik being a Learning 2.0 project to encourage library staff to experiment and learn about the new and emerging Internet technologies.

During the library 2.0 course I learned the basics of blogging, chatting, RSS, Podcasts, Wiki’s and social bookmarking. Each week another item was addressed. This learning program had a direct and positive impact. For instance, I could inform my clients how to create a RSS-feed for PubMed searches. By taking RSS-feeds/email alerts to interesting blogs, wiki’s and journals I kept better informed.

Hard to imagine (now) that I hardly new anything about web 2.0 one year ago.

Web 2.0 is not just a set of tools.

In the beginning I considered blogging largely as a selfish activity. It also appeared a lonely activity. As long as we discussed a course assignment there always was an interaction with at least a handful of other participants. But as soon as the program came to an end, I started to write more and more about medicine, EBM and medical library related matter, which didn’t appeal to most of the other course members. I wrote about things that interested me, but the writing would be absolutely useless if nobody would read it. Thus, how to get an audience?

There were I few things I had to learn and there were a few people who gave me a push in the right direction .

  • Wowter, who gave feedback to my posts right from the start and who encouraged me to continue blogging, posted a list with 17 tips for beginning bloggers (in Dutch) of how to increase visibility and findability of your blog. I became aware that ‘linking’ to others is what is making the web 2.0 world interconnected.
  • Second Dymphie, a Dutch Medical Librarian, encouraged me to start twittering. It took quite a while before I grasped the value of twitter as a networking tool. Twitter is not meant to say “what you do”, but it is a way to share information of any kind. Before you can share it, you first have to find interesting tweeple (people on twitter) and it did take a while before they followed me back (partly because my first tweets weren’t that interesting). Thus I had to learn by trial and error how to become a prolific twitterer.
  • Third I read a very interesting blogpost on “I’m not a geek” of Hutch Carpenter called Becoming a web 2.0 jedi, showing a simple but very accurate chart of the ever deeper levels of involvement one can have with Web 2.0 apps and the Web 2.0 ethos, as Hutch calls them. “Down are the lower levels, those of passive involvement, level 2 is giving up little pieces of yourself, while level 3 is a much bigger sharing experience. Share your own life, share your knowledge, share the stuff you find interesting. A big leap for a lot of us used to being more private. May the force be with you.”
    Seeing his post I realized that my journey had been quite different (figure below, made in September 2008). During the Spoetnik course emphasis was given to the tools themselves not to the ways you should use and share them and contribute to others. We skipped the reading of blogs and wiki’s, the lurking on twitter, but started with chatting, RSS and blogging. Although Web 2.0 tools are the basis, Web 2.0 is more an attitude than the usage of tools, it is about sharing information and thoughts.Or as Dean Giustini says it: It is about people.

The Ecosphere of Twitter and blogs.

I also experienced that all web 2.0 tools are not stand-alone tools, but can reinforce each other. This is for instance true for RSS, bookmarking tools , blogs, but also twitter (a microblogging service). A recent post of Sandnsurf (Mike Cadogan) at Life in the fast Lane uses a brilliant ecosystem metaphore to describe the twitter-blogging relationship. He describes the blogging ecosphere, where twitter decomposes information from journal articles and long blog posts into readily digestible information (nutrients and humus). See Figure from his post below (but read his post here for the whole story). Just like the Jedi chart this diagram illustrate exactly what web 2.0 is about.

Lessons to be learned

I have learned a lot. Am I now a real web 2.0 Jedi?
I’m not sure. In the ecology-model my blog is a young tree, surrounded by many others. But some ecologic dangers are luring.

  • The relative success of my blog results in “an abundance of light which results in a pressure to keep producing enough good quality posts”.
  • I’ve subscribed to so many RSS-feeds I seldomly read them.
  • I have so many twitter-followers (app. 300) that I can’t keep up with all of them as much as I would like to.
  • I read so many things, but haven’t got the time to work them out (or I simply forget).
  • I find it difficult to separate chaff from wheat. Many blogposts and web 2.0 information are not very accurate and superficial. Furthermore people often echo a subject without careful checking or without adding value.

Or in the words of sandnsurf: the death of a blog can ensue due to excessive exposure and Twittaholism. I hope It will not go in that direction, but I have to figure out a way to coop with the overwhelming amount of information and find a balance. That will be part of my (web 2.0) learning process in 2009.

One other thing:

I forgot to mention one very important experience. During my web 2.0 journey I virtually met many interesting, kind and helpful people from all over the world, from US, UK, Eastern Europe to India and Australia. Closer to home I also ‘met’ many very nice Dutch and Belgian people. I never liked the idea of intentional networking, but in web 2.0 the networks arise spontaneously. In a very natural and gradual way I became a member of a large health and library community and that feels good.

You might also want to read:





The Web 2.0-EBM Medicine split. [1] Introduction into a short series.

4 01 2009

Since the three years I’m working as a medical information specialist, I’ve embraced the concept of evidence based medicine or EBM. As a searcher I spend hours if not days to find as much relevant evidence as possible on a particular subject, which others select, appraise and synthesize to a systematic review or an evidence based guideline. I’m convinced that it is important to find the best evidence for any given intervention, diagnosis, prognostic or causal factor.

Why? Because history has shown that despite their expertise and best intentions, doctors don’t always know or feel what’s best for their patients.

An example. For many years corticosteroids had been used to lower intracranial pressure after serious head injury, because steroids reduce the inflammation that causes the brain to swell. However, in the 1990’s, meta-analyses and evidence-based guidelines called the effectiveness of steroids into question. Because of the lack of sufficiently large trials, a large RCT (CRASH) was started. Contrary to all expectations, there was actually an excess of 159 deaths in the steroid group. The overall absolute risk of death in the corticosteroid group was shown to be increased with 2%. This means that the administration of corticosteroids had caused more than 10,000 deaths before the 1990’s.[1,2,3]

Another example. The first Cochrane Systematic Review, shows the results of a systematic review of RCTs of a short, inexpensive course of a corticosteroid given to women about to give birth too early. The diagram below, which is nowadays well known as the logo of the Cochrane Collaboration, clearly shows that antenatal corticosteroids reduce the odds of the babies dying from the complications of immaturity by 30 to 50 per cent (diamond left under). Strikingly, the first of these RCTs showing a positive effect of corticosteroids, was already reported in 1972. By 1991, seven more trials had been reported, and the picture had become still stronger. Because no systematic review of these trials had been published until 1989, most obstetricians had not realized that the treatment was so effective. As a result, 10.000s of premature babies have probably suffered and died unnecessarily. This is just one of many examples of the human costs resulting from failure to perform systematic, up-to-date reviews of RCTs of health care.[4,5]

The Cochrane logo explained

Less than I year ago I entered the web 2.0-, and (indirectly) medicine 2.0 world, via a library 2.0 course. I loved the tools and I appreciated the approach. Web 2.0 is ‘all about sharing‘ or as Dean Giustini says it: ‘all about people. It is very fast and simple. It is easy to keep abreast of new information and to meet new interesting people with good ideas and a lot of knowledge.

An example. Bertalan Mesko in a comment on his blog ScienceRoll:

I know exactly that most of these web 2.0 tools have been around for quite a long time. Most of these things are not new and regarding the software, there aren’t any differences in most of the cases. But!
These tools and services will help us how to change medicine. In my opinion, the most essential problem of medicine nowadays is the sharing of information. Some months ago, I wrote about a blogger who fights Pompe disease, a rare genetic disorder and he told me about the diagnostic delay. I try to help physicians how they can find information easier and faster. For example: I gave tips how to search for genetic diseases.

Other examples are good functioning and dedicated patient web 2.0 sites, like PatientsLikeMe.

In the medical literature, blogs and slideshare, differences between medicine 2.0 and 1.0 are already described in detail (for instance see the excellent review of Dean Giustini in the BMJ), as well as the differences between medicine 1.0 and EBM (e.g. see the review of David Sackett et al in BMJ).

However, the longer I’m involved in web 2.0, the more I feel it conflicts with my job as EBM-librarian. The approach is so much different, other tools are used and other views shared. More and more I find ideas and opinions expressed on blogs that do EBM no justice and that seem to arise out of ignorance and/or prejudice. On the other hand EBM and traditional medicine often are not aware of web 2.0 sources or mistrust them. In science, blogs and wiki’s seldom count, because they express personal views, echo pre-existing data and are superficial.

split-1231

I’m feeling like I’m in a split, with one leg in EBM and the other in web 2.0. In my view each has got his merits, and these approaches should not oppose each other but should mingle. EBM getting a lower threshold and becoming more digestible and practical, and medicine 2.0 becoming less superficial and more underpinned.

It is my goal to take an upright position, standing on both legs, integrating EBM, medicine 2.0 (as well as medicine 1.0).

As a first step I will discuss some discrepancies between the two views as I encounter it in blogs, in the form of a mini-series: “The Web 2.0-EBM Medicine split”.

Before I do so I will give a short list of what I consider characteristic for each type of medicine, EBM-, Web 1.0 (usual)- and Web 2.0- medicine. Not based on any evidence, only on experience and intuition. I’ve just written down what came to my mind. I would be very interested in your thoughts on this.

EBM – medicine

  • centered round the best evidence
  • methodology-dependent
  • objective, transparent
  • thorough
  • difficult (to make, but for many also to find and also to understand)
  • time-consuming
  • published in peer reviewed papers (except for guidelines)
  • searching: PubMed and other bibliographic databases (to produce) and guideline databases, TRIP, and PubMed (Clinical Queries) or specific sources, i.e. specialist guidelines (to find).
  • Mostly Web 1.0 (with some web 2.0 tools, like podcasts, RSS and e-learning)

Web 1.0 – traditional medicine*

  • centered round clinical knowledge, expertise and intuition
  • opinion-based
  • authority based, i.e.strong beliefs in opinion leaders, expert opinion or ‘authority opinion’ (i.e. head of departments, professor) and own authority versus patient.
  • subjective
  • fast
  • act! (motto)
  • searching: browsing ( a specific list, site or Journals), quick search, mostly via Google**, in pharmacopeia, or protocols and UpToDate seldom in Pubmed (dependent on discipline)
  • Web 1.0: mail, patient-records, quick search via Google and Pubmed

Web 2.0 medicine

  • people-centered and patient-centered (although mostly not in individual blogs of doctors)
  • heavily based on technology (easy to use and free internet software)
  • social-based: based on sharing knowledge and expertise
  • (in theory) personalized
  • subjective, nondirected.
  • often:superficial
  • fast
  • generally not peer reviewed, i.e. published on blogs and wiki’s
  • searching: mostly via free internet sources and search engines, e.g. wikipedia, emedicine, respectively Google**, health metasearch engines, like Mednar and Health Sciences Online. PubMed mainly via third-party-tools like GoPubMed, HubMed and PubReminer. (e.g. see recent listings of top bedside health search engines on Sandnsurf’s blog ‘Life in the Fast Lane’
  • heavily dependent on web 2.0 tools both for ‘publishing’, ‘finding information’ and ‘communication’

*very general. of course dependent on discipline.
** this is not merely my impression, e.g. see: this blogpost on the “Clinical Cases and Images blog” of Ves Dimov, referring to four separate interviews of Dean Giustini with Physician bloggers.

Other references

[1] Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Edwards P et al. Lancet. 2005 Jun 4-10;365(9475):1957-9.
[2] A CRASH landing in severe head injury. Sauerland S, Maegele M. Lancet. 2004 Oct 9-15;364(9442):1291-2. Comment on: Lancet. 2004 Oct 9-15;364(9442):1321-8.
[3] Corticosteroids for acute traumatic brain injury.Alderson P, Roberts IG. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD000196.
[4] http://www.cochrane.org/logo/
[5] Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.Roberts D, Dalziel SR.Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004454
[6] How Web 2.0 is changing medicine. Giustini D. BMJ. 2006 Dec 23;333(7582):1283-4.
[7] Evidence based medicine: what it is and what it isn’t. Sackett DL et al. BMJ. 1996 Jan 13;312(7023):71-2.






Evolution and Medicine. Cancer and adaptive immune responses as evolutions ‘within’.

29 12 2008

I had almost finished my submission for the Grand Round when I took a look at the site of the host, Moneduloides*, to find that this edition had “the interface of evolution and medicine” as a theme.

What should I write about, considering I only had a few hours to write about this difficult theme?

Quite coincidentally (or not, considering the forthcoming bicentenary of Darwin’s birth (1809) and the 150th anniversary of the publication of ‘On the Origin of Species’) the December 2008 Lancet is a Special Issue: Darwin’s Gifts. But it would be to easy to just summarize one or two articles from this Lancet issue…

Evolution and Medicine can be interpreted differently. One can just see it as the evolution of medicine. Enough to write about this theme….

One can also see the theme in the light of consequences of evolution on medicine or illnesses. Indeed there are ample examples of the consequences of men’s evolution on the susceptibility to certain illnesses, e.g. see moneduloides’ blog about the consequence of human bipedalism.

Yesterday @carlosrizo (twitter) pointed out a link to Darwinian Medicine 2.0″. Since this would be of special interest to this web 2.0 audience, I took a look to see if I could ‘use’ this blogpost. However the post appeared to be based on a rather distorted interpretation of natural selection. Darwinian Medicine 1.0. is considered synonymous with eugenics (!), whereas Darwinian Medicine 2.0 is “gentler, interested in finding “evolutionary causes and remedies for diseases.” while leaving out the genocide”. The counterpart blog being intelligentdesign.org. it is easy to position their view.

Although this blog merits no further discussion, it highlights the often wrong interpretations of the natural selection theories. Eugenics is “just” a political interpretation by some of Darwin’s theorie (see Wikipedia). Darwin himself thought it “absurd to talk of one animal being higher than another” and saw evolution as having no goal.

As a biologist I grew up with the following definition of natural selection.

Natural selection is the process by which favorable heritable traits become more common in successive generations of a population of reproducing organisms, and unfavorable heritable traits become less common, due to differential reproduction of genotypes.

In other words natural selection genetic alterations are mostly random and chance (environment, conditions) will determine whether the genotype exhibiting a new phenotype will continue to exist or even will be more likely to survive (natural selection).

Antibiotic resistance
During my biology study we did all kind of mini-evolution experiments. For instance, we treated bacteria that were deficient for a specific amino-acid (AA) with mutagens and plated them on solid agar plates with or without that particular AA. Only bacteria with a mutation making them independent of that AA would survive on AA-less plates.

Although this is not an experiment of nature, a very similar example of natural selection in action is the development of antibiotic resistance in microorganisms (see wikipedia).

natural-selection-90

Enhancement of antibiotic resistance by natural selection - modified from wikipedia

Natural populations of bacteria contain considerable variation in their genetic material, primarily as the result of mutations. When exposed to antibiotics, most bacteria die quickly, but some (red in Figure) may have mutations that make them less susceptible. If the exposure to antibiotics is short, these individuals will survive the treatment. This selective elimination of maladapted individuals (lighter colors) from a population is natural selection.

Evolutions within
It is not difficult to see how infectious diseases were driven by natural selection (of the organisms causing these diseases). Because all rules that apply to eukaryotic organisms apply to prokaryotic organisms as well. But I would make a point that evolution and natural selection also takes place at a lower level: that of viruses (non-living organisms, see post about sputnik-virus here) and of “individual cells” within an organism. That is to say: the same mechanisms apply.

Clonal selection and B-cell adaptive immune response.
One example of a cellular evolution is the development of the B cell (and T cell) immune repertoire. B and T cells are cells of
the adaptive immune response. In contrast to the innate immune response, which is always ready to respond to whatever intruder, the adaptive immune response matures throughout life, is antigen-specific and long-living. The specificity of B cells lies in the variable region of their immunoglobulins or antibodies, Y-like molecules, anchored in the B cells’ plasma membrane. There are endless antibody variants and each B cell (and its progeny) produces antibodies with one particular specificity.
How is this diversity established?
In the Pre-B cell phase, when B cells do not produce any immunoglobulins individual gene segments coding for the V, (D) and J regions of the heavy and light chain of the immunoglobulin molecule are randomly assembled to one molecule. The random assembly of 51 V, 27 D and 6 J gene segments provides a minimum of 8.300 different possible combinations for the heavy chain alone, but since the recombination process is not precise and extra nucleotides are inserted the number of possibilities of antibody V region diversity turn out to be greater than that.[2]
(The following excellent animation is recommended: www.blink.biz/immunoanimations/ (be sure to choose Open > Antigen Recognition > Recombination)

vdj-recombination-2

When an organism encounters a foreign microorganism or other antigen, only those B cells that recognize the antigen are stimulated to divide and to become plasma cells which produce many antibodies specific for the particular antigen. This process is called clonal selection. It results in a B cell repertoire skewed towards the antigens encountered in life. The advantage is that those B cells are selected that have been proved useful. The next time the same antigen is encountered the response is quicker, stronger and more specific, a process called memory.This is also the principle behind vaccination and boostering.

The principle of clonal B cell selection is very similar to the development of antibiotic resistance, discussed above.

clonal-selection-users-path

Carcinogenesis: Follicular Lymphoma
However, sometimes clones are selected that erroneously react with ‘self’ which results in ‘autoimmunity‘.

Cancer can also be considered as another faulty ‘evolution’, be it within the organism. Cancer cells are better at surviving and reproducing than other cells, because they have escaped the body’s controls. This allows them to increase their population much faster than other cells.

In an interesting editorial, J Breivik comments on the work of Vineis and Berwick[4,5]:

Vineis and Berwick argue that ‘Carcinogenesis, at least for some types of cancer, can be interpreted as the consequence of selection of mutated cells similar to what, in the theory of evolution, occurs at the population level’. Taking a more conclusive stand, I will ague that carcinogenesis is an evolutionary process within the multicellular organism. Evolution by means of natural selection is a scientific principle that reaches far beyond the origin of the species and is applicable to all systems of inheritance, including somatic development.

One example is follicular lymphoma (FL). Follicular lymphoma is characterized by a chromosomal translocation between chromosome 14 and 18, t(14;18), caused by a faulty coupling of the immunoglobulin heavy J chain to the BCL-2 proto-oncogene on chromosome 14 during the normal VDJ-rearrangement process, described above. This mistake leads to a constitutive overexpression of BCL-2, which makes the cell less vulnerable to apoptosis (programmed cell death). Mice bearing a transgene mimicking the BCL-2 translocation have an increased incidence of spontaneous B lymphoid tumors. The lymphomas take many months to develop, however, and the penetrance of disease is low, arguing that BCL-2 overexpression on its own is not highly oncogenic (reviewed in[6]). Indeed our group has shown many years ago that t(14;18) translocations, that were considered specific for follicular lymphoma generally occur in follicular hyperplasias [7] and even in B-cells of healthy individuals [8]. Apparently B cells with the t(14;18) translocation are regularly generated in normal individuals, but only very few cells with the translocation will acquire the additional oncogenic hits necessary to establish the malignant phenotype. Overexpression of BCL-2 only gives the cells a survival advantage. Indeed, according to recent insights [9]:

“Accumulation of genomic alterations and clonal selection account for subsequent progression and transformation. Recently, the role of the immunologic microenvironment of FL in determining clinical behavior and prognosis has been substantiated. Combined genetic and immunologic data may now support a model for the development of FL as a disease of functional B cells in which specific molecular alterations infer intrinsic growth properties of the tumor cells as well as dictate a specific functional cross talk with the immunologic regulatory network resulting in extrinsic growth support.”

The theme of this week inspired me to philosophize about immunity and cancer being examples of evolutionary process. While reading I found that this idea is by no means new; a lot has been written about this concept. For instance in “Understanding Evolution” the writer(s) quite nicely explain the process of evolution within a cell lineage. They first explain that the key elements of the evolutionary process – variation, inheritance, and selective advantage – characterize not just populations of organisms in a particular environment, but also populations of cells within our own bodies.
Furthermore they make the interesting statement that

cancer – even within one person – isn’t a single entity. It’s a diverse and evolving population of cell lineages. A single tumor, for example, is made up of a variety of cell types, produced as the cells proliferated and incurred different mutations. All of this diversity means that the population of cells could easily include a mutant variety that happens to be resistant to any individual chemotherapy drug we might administer. To make matters even more difficult, treating the patient with that drug creates an environment in which the few resistant cancer cells have a strong selective advantage in comparison to other cells. Over time, those resistant cells will increase in frequency and continue to evolve. It’s not surprising then that a simple cure for cancer has yet to be developed: treating even a single type of cancer is a bit like trying to take aim at a whole set of moving targets all at once”

Thus, this challenge helps explain why research has not yet provided us with a cure, but also points the way toward new solutions that take that evolution into account ….

Sources:

  1. Wikipedia (several pages, as indicated)
  2. Kimball Biology Pages: [A] AgReceptorDiversity (very good background information in dictionary-format)
  3. Evolving Immunity – A Response to Chapter 6 of Darwin’s Black Box. Matt Inlay. [blog] Talkdesign: interesting discussion on whether or not clonal selection system could have evolved in the context of irreducible complexity.
  4. Cancer the evolution-within, by Dan [blogpost] on Migrations (2007/04/18) referring to:
  5. Cancer – evolution within. Breivik, J. Int. J. Epidemiol. (2006) 35, 1161-1162.
  6. The Bcl-2 family: roles in cell survival and oncogenesis. Suzanne Cory1, David C S Huang1 and Jerry M Adam. Oncogene (2003) 22, 8590-8607.
  7. Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia. Limpens J, de Jong D, van Krieken JH, Price CG, Young BD, van Ommen GJ, Kluin PM. Oncogene. 1991 Dec;6(12):2271-6.(PubMed-link)(
  8. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Limpens J, Stad R, Vos C, de Vlaam C, de Jong D, van Ommen GJ, Schuuring E, Kluin PM. Blood. 1995 May 1;85(9):2528-36.(PubMed-link)(Google Scholar)
  9. Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors. de Jong D. J Clin Oncol. 2005 Sep 10;23(26):6358-63.(PubMed-link)
  10. Another perspective on cancer: Evolution within. [blog] Understanding Evolution with a detailed description on natural selection within, and the evolution of cancer cells plus possible solutions.

Figures:

  1. Antibiotic Resistance: wikipedia
  2. Clonal Selection: http://users.path.ox.ac.uk/~scobbold/tig/clons.gif
  3. Recombination: Evolving Immunity – A Response to Chapter 6 of Darwin’s Black Box, adapted from janeway






Laika’s Little Party

21 09 2008

It’s time for some reflections on this blog and for a little party. Why?

So for now I will start with the party (with some wine), the reflections will follow when I’m sober.

This week I received an unexpected email from RNCentral (“the place to learn about nursing online”), anouncing that this blog had made it to the “Top 50 Health 2.0 Blogs list ( see here).

The top 50 health 2.0 list is not based on a kind of “objective” ranking like the Healthcare 100 or MedBlogEN lists, which are a measure of how many people link to your site, find your site by searching or have subscribed to your blogposts: thus an indirect measure of “how popular you are“. In such a list I would not make the top-100.
The RNCental site gives a “subjective” top 50 list of blogs, that appear valuable to the authors. The list is introduced with a very nice definition of health 2.0 blogs, that I can subscribe to:

Health 2.0 embraces the idea of bringing health care into the community of physicians, patients, and those in the health care industry together with technology and the Internet to provide the best possible health care environment. What better way for the various parts of this community to share their thoughts and communicate ideas than through their blogs? From corporate blogs to blogs that are a part of social networks to individual blogs touching on technology or health care policy, these blogs will help bring you into the community, provide information and resources, and may perhaps help you find your voice as well.

I’m thrilled that I’m (literally) placed next to David Rothman in the “Health and Technology”-section. Although, to be honest, I see myself as a true beginner in this web 2.0 world and I learn a lot of established web 2.0 experts like David Rothman, KraftyLibrarian, Berci of Science Roll, MD Anderson on Emerging Technologies Librarian, Dean Giustini (UBC Academic Search), Sachet62 on Twitter, symtym from symtym.com, David Bradley from Sciencebase and Dutch colleagues like Wowter (with a dutch and an english blog), Dymphie (Dee’tjes) and many many more. On my blog I try to integrate what I learn elsewhere (articles, posts, twitter messages) with my own knowledge and interest.

The resultant is a rather diverse mixture of subjects in the field of (medical) librarianship, medicine, health (including consumers), evidence based medicine and web 2.0 tools.

Although such a broad mixture might not be appealing to everyone, it is appreciated by some, as is apparent from a recent blog-review in the Library + Information Gazette, 22 August 2008: p5 (UK). The Gazette is only available in print edition and I wouldn’t have known about it if Anne Welsh of “First Person Narrative” had not mentioned it at her blog (see post: “mainstreaming blogs as information sources”). Anne:

“This review is the first in a series “Blog Spotlight” authored by Danielle Worster (the Health Informaticist). It’s aim is to help separating the wheat from the chaff when it comes to blogs in LIS and health informatics.

Any blog that claims to be about information, research, Web 2.0 or health informatics is considered. Each blog discussed is described in terms of its audience, currency, informativeness, authoritativeness / credibility, readability and design, with a brief overview and summary. It’s a nice format, and starts well in this issue with UBC Academic Search , ResearchBuzz and Laika’s MedLibLog.”

With Anne I find it regretful that the gazette is not available online. I surely would like to follow this series.

Luckily I found Keith Nockels (Browsing) willing to make a scan of the Gazette’s review and send it to me.

The Gazette review sketched my blog with very flattering sentences (“colourful, engaging and relevant”, “easy to read and digest”) as well as apt descriptions, which made me grin: “while it does stray to discuss….. Although she writes copious amounts, it is as easy to skim as to read it all…. crammed full of visuals.”

And about Dean’s UBC Academic Blog:

“Very informative: has an uncanny ability to pick up on crucial issue”. …. the blogger’s energy comes through in his shorter sentences….. essential reading.” All true! Dean’s blog is a must in the librarian web 2.0 world!

Apart from these official listings and reviews I got some comments or links that were also heartwarming.

For instance Keith Nockels (a UK Librarian with a nice blog (“Browsing”), apparently familiar with at least a few Dutch words) refers so nicely in his blogpost “More about changes to Ovid”:

“I have since found a posting on Laikas MedLibLog about this, and Laika has obviously looked at this properly! So, I can now report that you (….)
Laikas posting is here (in English and ook in Nederlands) and is gratefully acknowledged. She talks about other things besides, so please read her posting for more!”

And Dr. Shock announcement of the dutch grand round number 1:

Laika Spoetnik presents The Best Study Design… For Dummies (in English).
She writes in English and Dutch so you have no excuse for not reading this excellent post. She clearly explains Randomized Controlled Trials (RCT’s) and the levels of evidence. She uses an example which is easy to follow: Does beta carotene prevent lung cancer.

At Medliblog (the official website of the BMI, Dutch Biomedical Information) Annie (writing about Evidence Based Dietetics refers to the same post, saying:

….handige bijlages met een checklist voor het lezen van wetenschappelijke artikelen en een statistische begrippenlijst, dat laatste blijft toch altijd wel moeilijke stof voor dummies of alfa’s.
Voor die categorie heeft Laika een zeer begrijpelijke blog (zowel Engels- als Nederlandstalig) geschreven, waarvoor mijn dank. Zo’n presentatie zou ik ook wel willen bijwonen.

meaning:

For that category (dummies or alpha people not understanding checklists and studytypes) Laika has written a very comprehensible blogpost (in English and Dutch), for which I would like to thank her. I would have loved to attend such a presentation. (I gave to historians about “how doctors search”).

These comments strengthen me to continue blogging. This is why I blog: that (some) people like to read what I write and learn from some of the posts.

Well that is probably enough shameless self-glorification for now. I do realize that beginners get mild critiques, but as you get more well known the expectations will grow along and the critiques as well.

Next time, at request of Wowter, I will reflect more on the 5W’s of this blog: why, when, who, what, where?





Randy Pausch Last Lecture: Achieving Your Childhood Dreams

26 07 2008

**********************************************************************
For people just looking for video’s, powerpoints or transcripts of Randy’s presentation(s), the most important links are these:

http://download.srv.cs.cmu.edu/~pausch/ Randy Pausch’s Web Site on Carnegie Mellon University, i.e. with links to transcripts and powerpoint-presentation (low resolution, used in this post) of his lectures.

http://www.cs.virginia.edu/~robins/Randy/ ” The Legacy of Randy Pausch” Dr. Gabriel Robins, colleague Professor, mentor and friend. With additional interesting links
http://www.cmu.edu/randyslecture/ about Randy Pausch’s Last Lecture
http://www.alice.org/
link to Alice
the video’s are shown below,

***********************************************************************

The other day I wrote about Twitter as an alternative and sometimes breaking news source.

That same day this news reached me via twitterer @Mndoci (Deepak Singh):

Randy Pausch. I didn’t know who that was, so I googled him.

There is a full record in Wikipedia, which is VERY up to date: Randolph Frederick Pausch (October 23, 1960 – July 25, 2008) was an American professor of computer science, human computer interaction and design at Carnegie Mellon University (CMU) in Pittsburgh..and a bestselling author who achieved worldwide fame for his The Last Lecture” speech on September 18, 2007 at Carnegie Mellon.

His “Last Lecture” was viewed online by over six million people and has been recently been published as a book (see Librarything description).

When he held the speech, he knew he had just a few months to live: the pancreatic cancer he was diagnosed with a year before had spread to other organs. He decided not to play it very emotional, but to go for dark humor.

This is how he starts his Last Lecture (which ironically had recently been renamed as ‘Journeys’). It sets the tone for the rest of the presentation:

What Indira didn’t tell you is that this lecture series used to be called the Last Lecture. If you had one last lecture to give before you died, what would it be? I thought, damn, I finally nailed the venue and they renamed it. [laughter] So, you know, in case there’s anybody who wandered in and doesn’t know the back story, my dad always taught me that when there’s an elephant in the room, introduce them. If you look at my CAT scans, there are approximately 10 tumors in my liver, and the doctors told me 3-6 months of good health left. That was a month ago, so you can do the math. … We can’t change it, and we just have to decide how we’re going to respond to that. We cannot change the cards we are dealt, just how we play the hand. If I don’t seem as depressed or morose as I should be, sorry to disappoint you. [laughter] And I assure you I am not in denial. It’s not like I’m not aware of what’s going on….”

He ends the lecture entitled “Really Achieving Your Childhood Dreams” like this:

So today’s talk was about my childhood dreams, enabling the dreams of others, and some lessons learned. But did you figure out the head fake? [dramatic pause] It’s not about how to achieve your dreams. It’s about how to lead your life. If you lead your life the right way, the karma will take care of itself. The dreams will come to you. Have you figured out the second head fake? The talk’s not for you, it’s for my kids. Thank you all,good night

I found his speech very inspiring. A mixture of amusing stories and wise life lessons. Not just theories but real examples illustrating his points. Very clear and recognizable. His main theme: Brick walls are there for a reason: they let us prove how badly we want things. He showed how most of his dreams were realized (or dealt with or ‘adapted’: ‘Being Captain Kirk’ was changed in ‘Meeting Captain Kirk’), the magic word being perseverance: “never give up!”. Other one-liners: “Loyalty is a two way street”. “Give people enough time and they will always impress you”.

He learned a lot from other people. This is what he learned from his football coach when he was 9 years old:

“And he showed up for practice the first day, and you know, there’s big hulking guy, we were all scared to death of him. And he hadn’t brought any footballs. How are we going to have practice without any footballs? And one of the other kids said, excuse me coach, but there’s no football. And Coach Graham said, right, how many men are on a football field at a time? Eleven on a team, twenty-two. Coach Graham said, all right, and how many people are touching the football at any given time? One of them. And he said, right, so we’re going to work on what those other twenty-one guys are doing. And that’s a really good story because it’s all about fundamentals. Fundamentals, fundamentals, fundamentals. You’ve got to get the fundamentals down because otherwise the fancy stuff isn’t going to work.”

He also stresses that it’s not what you say but how you say it (“c’est le ton qui fait la musique”). Here he tells a story about how his dutch uncle and first boss Andy ‘beats him up’.

“He Dutch-uncled me. And he put his arm around my shoulders and we went for a little walk and he said, Randy, it’s such a shame that people perceive you as so arrogant. Because it’s going to limit what you’re going to be able to accomplish in life. What a hell of a way to word “you’re being a jerk.” [laughter] Right? He doesn’t say you’re a jerk…”

The same uncle stimulated him to do his PhD instead of taking a job:

“It wasn’t the kind of thing people from my family did. We got, say, what do you call them? …. jobs. And Andy said, no, don’t go do that. Go get a Ph.D. Become a professor. And I said, why? And he said, because you’re such a good salesman that any company that gets you is going to use you as a salesman. And you might as well be selling something worthwhile like education.[long pause, looks directly at Andy van Dam] Thanks.”

He did do his PhD and became a charming professor, a brilliant researcher ànd a gifted teacher. His specialty was virtual reality. He was able to mix theorie and practice in a very fruitful way. For instance he combined his work as a professor of Computer Science, Human-Computer Interaction, and Design at Carnegie Mellon with Sabbaticals at Walt Disney Imagineering and Electronic Arts (EA) (one of his childhood dreams) and he became co-founder of Carnegie Mellon’s Entertainment Technology Center (ETC). He also was the director of the Alice (www.alice.org), a software project ‘learning’ children to program while they just think they’re making movies and video games. The good stuff is coming in the next version, where we will teach them Java language while they think they are writing moviescripts using Sims characters, Randy said.

“I, like Moses, get to see the promised land, but I won’t getto set foot in it. And that’s OK, because I can see it. And the vision is clear. Millions of kids having fun while learning something hard. That’s pretty cool. I can deal with that as a legacy.”

And what a legacy this is. Randy’s wife, Jai, put out a statement the day he died thanking “the millions of people who have offered their love, prayers and support. Randy was so happy and proud that the lecture and book inspired parents to revisit their priorities, particularly their relationships with their children,” she said. “The outpouring of cards and e-mails really sustained him.” (Foxnews, July 28th)

Please enjoy the videos and/or go to links below where you can find more information.

Vodpod videos no longer available.

more about “Randy Pausch Last Lecture: Achieving …“, posted with vodpod

Apart from his last lecture I also include his lecture on time management. This was something Randy also was an expert in. I’m sure it will be very inspiring as well.

Vodpod videos no longer available.

Miscelanous Sources (other than referred to above)

NL flag NL vlag

Eerder schreef ik dat Twitter soms een heel goede en snelle nieuwsbron kan zijn.

Diezelfde dag las ik de volgende twitter van @Mndoci:

Randy Pausch. Ik had eerlijk gezegd geen idee wie het was, dus heb even gegoogled.

Er is een volledige pagina in Wikipedia, over Pausch, die nogal erg up to date was: Randolph Frederick Pausch (October 23, 1960 – July 25, 2008) was an American professor of computer science, human computer interaction and design at Carnegie Mellon University (CMU) in Pittsburgh..and a bestselling author who achieved worldwide fame for his The Last Lecture” speech on September 18, 2007 at Carnegie Mellon.

Zijn “Laatste Lezing” werd zeker door meer dan 6 miljoen mensen bekeken en is recent als boek uitgebracht (zie Librarything).

Toen hij de toespraak hield had hij net te horen gekregen dat hij nog maar enkele maanden te leven had. De pancreaskanker (het jaar daarvoor bij hem vastgesteld) was uitgezaaid en niet meer behandelbaar. Hij had er heel emotioneel over kunnen doen, maar het lag meer in zijn aard om het met wat galgenhumor te brengen.

Ironisch genoeg was de naam ‘Last Lecture’ net gewijzigd in ‘Journeys’. De lezing heette de last lecture omdat je aan de studenten levenswijsheden zou onderwijzen alsof het de laatste mogelijkheid was: wat geef je mensen mee als je weet dat je nog maar kort te leven hebt? Maar nu was het letterlijk zo. Randy grapte meteen: nu ben ik eindelijk zover dat ik de lezing mag geven, veranderen ze de naam.

Zijn lezing heet “Really Achieving Your Childhood Dreams”. Hij vertelt hoe hij zijn kinderdromen heeft gerealiseerd of omgevormd (Captain Kirk zijn werd Captain Kirk ontmoeten, dat is gelukt). Sommige dromen die hij niet gerealiseerd heeft (premier league football player), hebben toch hun nut gehad omdat hij belangrijke zaken leerde, die hem later in zijn leven goed van pas zouden komen. Hij leerde bijvoorbeeld van zijn rugby-trainers hoe belangrijk het was te volharden: eerst de basis leggen, dan de vruchten plukken.

Zijn lezing gaat niet alleen erom hoe je je eigen dromen kunt verwezenlijken (of eigenlijk hoe je moet leven), maar ook hoe je die van anderen kunt verwezenlijken. Dat was zijn sterke punt.

Hij was van plan gewoon een baantje te nemen, zoals iedereen in zijn familie, maar op aanraden van een nederlandse oom ging hij studeren (computerwetenschappen), promoveerde hij en werd hij professor en nog belangrijker: een charmante persoonlijkheid, een briljante onderzoeker en een begenadigd leraar. Hij was gespecialiseerd in “virtual reality” en zag een van zijn kinderdromen (disney-imagineer) in vervulling gaan toen hij op vernuftige wijze zijn professoraat in Carnegie Mellon wist te combineren met (meerdere) Sabbaticals bij Walt Disney Imagineering and Electronic Arts (EA). Later zette hij zelf het Carnegie Mellon’s Entertainment Technology Center (ETC) op. Ook was hij directeur van Alice (www.alice.org), een software project dat kinderen ‘leert’ te programmeren, terwijl ze denken dat ze films en video’s maken. In de komende versie wordt kinderen geleerd met Java te werken terwijl ze denken dat ze scripts voor een film met Sims-figuren schrijven.

Het is een mooie nalatenschap, die Randy ons achterliet

“I, like Moses, get to see the promised land, but I won’t getto set foot in it. And that’s OK, because I can see it. And the vision is clear. Millions of kids having fun while learning something hard. That’s pretty cool. I can deal with that as a legacy.”

Voor details van zijn lezing verwijs ik verder graag naar de video’s, engelse citaten en verdere literatuurverwijzingen hierboven.





PubMed: Past, Present and Future PART III

27 06 2008

The Future: ????

This is a continuation of Part I and II

Part I (click here) describes that PubMed contains many different tools, some of which are quite difficult in use and/or hidden, i.e. Single Citation Matcher, MeSH database and Clinical Queries.

This counterintuitive character of the PubMed interface leads to Google-like searches, that are often ineffective, driving some people crazy. Anna Kushnir for instance started a little riot on her blog by shouting out loud that she hates PubMed. Her ranting elicited a response of Dr. Lipman of the NCBI who reassured her “that a number of changes are underway that will make PubMed work better for her and many other users”.

Part II (click here) describes the new PubMed features recently introduced to meet the wishes of an apparent majority of people that come to PubMed in search for specific information ‘with one finger snap’:

  • ATM has been modified to enable retrieval of citations: multi-word terms are split and sought individually in all fields, including author, address, journal-title field
  • Introduction of a Citation Sensor, that matches searches with citations
  • Advanced Search Beta that allows to specify fields for searching
  • Disappearance of the blue side bar to play along with new features.

These modifications facilitate retrieval of citations to some extent, though not as effectively as the ‘good old’ Single Citation Matcher and at the cost of effective subject searching. In particular, the renewed ATM leads to an unacceptable low precision (ample examples given).

Part III is about the future, but what the future has in store I do not know. I have some ideas though as to what I would like the (near) future to bring (or NLM/NCBI to change) :

[General]
People come to PubMed with different kinds of backgrounds, information skills, questions and aims. Rather than creating one tool that serves them all, but imperfectly, why not create different tools that serves each group well? Why replace Mercedes-cars by Flintstone-mobiles, because 90% of the people rather use their feet? Make 10% Mercedes or learn the Flintstones how to enjoy driving a real motor-driven car!
Thus make it easy on newbies and people just passing by, give them an idea what they might have missed and why, but still enable exhaustive subject searching for those that wish/need to do so. PubMed should not be just Google-like because people are used to that. Number one priority should be that people find what they are looking for! If this means that they have to do a little training: o.k., what’s wrong with that? I agree fully with David Rothman’s view on the anna-kushnir-when-the-user-actually-is-broken story as expressed in his excellent post. I particularly like the parable he gave:

“I remember asking my father to teach me to program in BASIC. He cheerfully agreed and handed me the big brown manual”

PubMed should not imitate its look-alikes, which do an awful lot better with regard to user-friendliness (see for instance here), but generally are NOT very suitable for (more exhaustive) medical subject searching.

[Specific]
At least disconnect reference and subject searching (please??…)

  • The Single Citation Matcher is a perfect tool that, when found, is easy to use for everyone. Why not give it a more self-evident name, like “reference-seeker” OR “find (the) citation” and put it in a more prominent place?
    If NLM/NCBI decides that the general search bar (or PubMed entrance) should be apt for citation searching, why not create a second one for subject searching? Perhaps give people (optional) tips how to continue:

Want to look up a reference: Go to the Single Citation Matcher.
Have a medical question? Go to the subject search bar (or -page).
Do you want to find the best evidence? Go to clinical queries.

Institutional or personal customization of the interface would be a pro. The OVID-SP interface has many of the above characteristics.

  • For subject searching, the old features suffice. Indeed:
    • Give back the blue side bar to reduce the number of clicks needed to (re)enter the MeSH-database, Clinical Queries, Single Citation Matcher etc.
    • Undo the new ATM feature! The only thing that is ‘enhanced’ is the number needed to read. It’s awful!
    • No Advanced Search Beta in the present form, only some of its features, like locking/unlocking some of the limits and multiple field-selection in the index.
      The idea of boxes is nice though.
      MeSH-fields should be default in any new (advanced) interface, as are Clinical Queries and the MeSH-database.
  • [Dreams]
    • Two different interfaces: for simple and for advanced searches. The first may look like advanced search beta (but with optional boxes), the second with an interface that facilitates comprehensive searching, i.e. staying within the History, powerful tools always one click away, easy navigating and sending terms from MeSH-database to PubMed (no ‘Send to Search Box’).
    • Possibility to save and edit the History and not just one search (like in OVID) and perhaps, perhaps, the adjacency function?
    • All important tools like MyNCBI, RSS, MeSH, more ‘visible and intuitive’ for all.
    • Modernization of MeSH (especially in the non-clinical field) and one MeSH for one concept, i.e. not: (Protein Kinase Inhibitors AND Receptor, Epidermal Growth Factor/antagonists & inhibitors) for EGFR tyrosine kinase inhibitors.

How can (some of) these changes be achieved? “Should I shout out loud: I hate PubMed” in order to be heard? No way. I like PubMed. In essence it is a powerful tool freely available to everyone.

But I hope that PubMed (NCBI/NLM) will not merely watch statistics and listen to the voice of the clamorous crowd, but will also listen to the few expert librarians, who represent a large community. They often know the information needs of our clients and the barrieres in the information-seeking process very well, since they help and train them every day…
—————————-

NL flag NL vlagDe toekomst: ????

Dit is een vervolg van deel I en II

Deel I (klik hier) bespreekt dat Pubmed veel zoekfuncties heeft die vaak nogal complex zijn en moeilijk te vinden, zoals de zoekbalk, de Single Citation Matcher, de MeSH-database en Clinical Queries.

Omdat PubMed zo ingewikkeld overkomt zoeken mensen veelal zoals in Google via de zoekbalk, met als gevolg dat het resultaat te wensen overlaat. Uit onwetendheid schuift men de schuld af op PubMed. Zo ging Anna Kushnir op haar weblog luid te keer dat ze PubMed haatte. Hierop reageerde Dr. Lipman (NCBI) met de mededeling: “a number of changes are underway that will make PubMed work better for her and many other users”.

Deel II ((klik hier) Beschrijft de nieuwe zoekfuncties, die recent zijn geintroduceerd om aan de wensen van die mensen tegemoet komen die kennelijk de meerderheid vormen: diegenen die snel even in PubMed zoeken om iets te vinden:

  • ATM is gewijzigd dat PubMed ook citaties kan vinden: Termen worden nu in alle velden gezocht en opgesplitst, indien ze uit meerdere woorden bestaan.
  • Citation Sensor, die citaties ‘herkent’.
  • Advanced Search Beta, waarin je op specifieke velden kunt zoeken.
  • Verdwijnen van de blauwe balk rechts.

Door deze veranderingen kunnen specifieke referenties soms iets beter gevonden worden, maar lang niet zo effectief als met de ‘oude vertrouwde’ Single Citation Matcher en ten koste van een onacceptabele hoeveelheid ruis, vooral door de nieuwe ATM.

Part III gaat over de toekomst. Wat die brengt weet ik natuurlijk niet. Wel weet ik wat ik graag zou willen dat er verandert.

[Algemeen]
PubMedgebruikers verschillen qua achtergrond, zoekvaardigheid, vragen en doelstelling. Waaorm zou je al deze mensen op dezelfde manier laten zoeken, waarom niet verschillende mogelijkheden voor verschillende gebruikers? Waarom zou je mercedes-auto’s willen vervangen door flinstone-auto’s, omdat 90% van de mensen liever zijn voeten gebruikt? Maak voor die 10% Mercedes-auto’s (of Opel Astra’s) of leer de Flintstones hoe ze moeten rijden in een auto die op benzine rijdt.
Maak het makkelijk voor beginners of mensen die eventjes iets zoeken, attendeer ze op wat ze misschien missen en waarom, maar laat het ook mogelijk blijven om op een makkelijke manier uitgebreide zoekacties te doen. PubMed moet toch niet op Google lijken, omdat mensen aan Google gewend zijn? Het allerbelangrijkste is dat mensen vinden waar ze naar zoeken. Als dat betekent dat ze zich er een beetje in moeten verdiepen, dan is dat toch o.k.?! Ik ben het helemaal met David Rothman’s visie op het Anna Kushnir gebeuren eens. Deze vergelijking is ook wel treffend:

“I remember asking my father to teach me to program in BASIC. He cheerfully agreed and handed me the big brown manual”

PubMed moet ook niet proberen zijn kopieen na te bootsen. Die zijn veel gebruikersvriendelijker (zie bijv hier), maar meestal niet bijzonder geschikt voor het uitgebreid zoeken op onderwerp. En dat is nu juist de meerwaarde van PubMed.

[Specifiek]
Koppel het zoeken van citaties los van het zoeken op onderwerp.

  • De Single Citation Matcher is uitermate geschikt voor het vinden van citaties en makkelijk in het gebruik. Het zou wat makkelijker te vinden moeten zijn en een vanzelfsprekender naam moeten hebben, zoals “reference-seeker” of “find (the) citation”.
    Als NLM/NCBI besluit dat de algemene zoekbalk vooral citaties moet kunnen vinden, waarom zou je dan geen 2e balk/pagina kunnen hebben om wel op onderwerp te zoeken? Misschien met wat (optionele) tips:

Want to look up a reference: Go to the Single Citation Matcher.
Have a medical question? Go to the subject search bar (or -page).
Do you want to find the best evidence? Go to clinical queries.

Het zou fijn zijn als je, net als bij OVID-SP, de default instellingen zou kunnen wijzigen.

  • V.w.b. het zoeken op onderwerp voldoet het oude PubMed eigenlijk grotendeels, dus:
    • Geef ons de blauwe menubalk terug! zodat we niet eindeloos moeten klikken om (weer) in de MeSH-database, Clinical Queries en Single Citation te komen.
    • Geef ons de oude ATM terug! Het enige wat ‘vooruit is gegaan’ is de “number needed to read”. Zoveel meer artikelen en zoveel meer ruis.
    • Niet een Advanced Search Beta, hooguit in een aangepaste vorm. Het vastzetten van bepaalde limieten, het kunnen selecteren van verschillende velden zijn goede aanpassingen.
      Ook de velden (voor zoeken, zoekgeschiedenis, limiteren e.d.) zijn geen slecht idee.
      MeSH-index-velden zouden standaard aanwezig moeten zijn, evenals Clinical Queries en MeSH-database.
  • [Dromen]
    • Twee verschillende interfaces voor beginners en gevorderden. De 1e zou op Advanced Search Beta mogen lijken (maar met MeSH-velden), de 2e zou uitgebreid zoeken mogelijk moeten maken. Je zou graag in de Zoekgeschiedenis willen blijven, alle belangrijke hulpmiddelen binnen bereik willen hebben en makkelijk willen navigeren vanuit PubMed naar de MeSH database en v.v. (niet via de ‘Send to Search box’ bijvoorbeeld).
    • De mogelijkheid om de hele zoekgeschiedenis te bewaren en te bewerken en misschien, misschien …. nabijheidszoeken (net als in OVID)?
    • Alle belangrijke zoekopties zoals MyNCBI, RSS, MeSH duidelijker zichtbaar en makkelijk in het gebruik.
    • Aanpassen van MeSH aan de moderne tijd/prekinische vakken en één MeSH voor één concept, bijv niet: (Protein Kinase Inhibitors AND Receptor, Epidermal Growth Factor/antagonists & inhibitors) om ‘EGFR tyrosine kinase inhibitors’ te vinden.

Hoe (enkele van) deze veranderingen te bereiken? Moet ik ook uitschreeuwen dat ik PubMed haat voor ik gehoord word?
Tuurlijk niet, ik haat PubMed niet. Het is prachtig dat zoiets als PubMed bestaat. In principe is het een geweldig goede database met heel veel mogelijkheden. En wat ook ook heel belangrijk is: het is gratis beschikbaar voor iedereen.

Maar ik hoop alleen dat de mensen achter PubMed (NCBI/NLM) niet alleen maar naar de statistieken kijken en naar de stem van de massa luisteren, maar ook de mening van informatiespecialisten ter harte nemen. Want zij vertegenwoordigen eigenlijk een heel grote groep gebruikers en weten uit ervaring waar hun klanten naar op zoek zijn en tegen welke problemen ze oplopen.





PubMed: Past, Present And Future, PART II

15 06 2008

The Present: PubMed is going for the mass.

This is a continuation of Part I (click here to read)

… Well, it seems that some of these enhancements are in the process of being implemented, considering recent major changes to PubMed’s interface:

1. Automatic Term Mapping (ATM).

ATM is the most recent, most radical and yet most poorly announced change.

Suddenly, when preparing a Master Class, searching via the search bar gave different, sometimes odd results. PubMed looked the same, but the DETAILS-tab showed the automatic search mapping (ATM) to be different. PubMed’s “New and Noteworthy” confirmed that ATM had been drastically modified. See here for the announcement’.

Consider this (given) example. Searching gene therapy would give:

with the Old ATM:
“gene therapy”[MeSH Terms] OR gene therapy[Text Word]

and the NEW ATM:
“gene therapy”[MeSH Terms] OR (“gene”[All Fields] AND “therapy”[All Fields]) OR “gene therapy”[All Fields].

Thus the new ATM expands the search:

1. by searching in All Fields instead of the tw-field (Title, Abstract, MeSH)
2. by splitting multi-word terms. Gene therapy is no longer sought as “gene therapy”, but as “gene” and “therapy”.

According to the NLM this facilitates finding synonyms like “gene silencing therapy…” and finding X in the author field. They should add: whether you WANT TO FIND IT OR NOT. Thus from now on you will search all fields automatically, including author, journal and address field.

Should I be glad to find more? NO, I use the Single Citation Mapper if I want to find a citation by author X, and I rather expand the search by adding terms that matter.
Suppose I would like to search´gene silencing therapy´ as well, then I would add gene silencing therap*[tiab], since searching for these words in a string will broaden the search without increasing noise.

However gene silencing (preventing a gene to work, i.e. by antisense oligo’s OR siRNA) is not really a gene therapy (insertion of a gene). So for most searches on ´gene therapy´ ´gene silencing´ is no valuable addition. And if it would be, MeSH like “Gene Silencing” and its narrow term RNA Interference should be included as well.

With gene therapy ATM will now (June 5th) retrieve 90942 hits instead of 36557, thus a surplus of 54385 hits, that is 2 ½ times as much!!! The expansion does add very little meaningful terms. It mainly retrieves citations with therapy in ANY field and:

  • gene as an author [au] : 53 extra hits
  • gene in the addressfield [ad], like hkj@gene.com or Department of Gene Regulation : 1327 extra hits
  • gene in the journal name, including “Gene” : 1487 extra hits
  • gene and therapy in the abstract/MeSH without direct connection to each other: papers about the impact of gene expression profiling on breast cancer outcomes (following chemotherapy NOT gene therapy), of experimental studies on change in gene-regulation following therapy etcetera: the majority of the extra hits. Estimation > 90%?: does anyone realize how often ‘gene’ and ‘therapy’ (in text, MeSH, subheadings and all other fields?) are used outside the context of gene therapy?

I guess I’m not the only one that is not pleased with this “enhancement”. Most users I know use Pubmed for subject searching and they unanimously experience the high number needed to read (high recall, low precision) as the major obstacle. ATM will only make this worse.

And what about:

  • people unaware of any changes and just relying on the search bar for subject searching, supposing it works the same as before?
  • the effect on alerts (RSS or MyNCBI)?
  • important updates of prior searches, i.e. for systematic reviews. With ATM you may retrieve MUCH more irrelevant papers. How to explain different results over time?
  • Although of minor importance, our courses, tutorials, exercises, the PubMed book my colleagues just wrote, all have to be adapted.

Thus I stop advising students/meds to simply use the search bar and just check the details, because this will surely frustate them. Rather I will advise them to add tags themselves: Look for the appropriate MeSH for Y in the MeSH-database and add Y*[tiab] as well. Even for simple subject searches!

Who wants the search d-dimer diagnosis lung embolism to be translated as:

(“fibrin fragment D”[Substance Name] OR (“fibrin”[All Fields] AND “fragment”[All Fields] AND “D”[All Fields]) OR “fibrin fragment D”[All Fields] OR (“d”[All Fields] AND “dimer”[All Fields]) OR “d dimer”[All Fields]) AND (“diagnosis”[Subheading] OR “diagnosis”[All Fields] OR “diagnosis”[MeSH Terms]) AND (“lung”[MeSH Terms] OR “lung”[All Fields]) AND (“embolism”[MeSH Terms] OR “embolism”[All Fields])

Very impressive, isn’t it, but the correct MeSH for lung embolism, pulmonary embolism is not mapped!!!!

Is it good then for preclinical guys, i.e.molecular biologist? Suppose you’re looking for signal transducer and activator of transcription 3 (that’s one protein), most lab people will use either the whole word or stat 3, stat(3), stat-3 or stat3

1. stat 3 maps to: (“Stat”[Journal] OR “stat”[All Fields]) AND 3[All Fields] = 4031 hits

2. Stat-3 maps to: stat-3[All Fields] = 591 hits

3. stat3 maps to: “stat3 transcription factor”[MeSH Terms] OR (“stat3″[All Fields] AND “transcription”[All Fields] AND “factor”[All Fields]) OR “stat3 transcription factor”[All Fields] OR “stat3″[All Fields] = 4639 hits
(Note that grey terms are superfluous: by searching stat3 you already find stat3 transcription factors)

Not very consistent and only the 3rd variation will be mapped to the proper MeSH, BUT (like 1.) will also give things like:

  • DeltaB=(1.18+/-0.09_{stat}+/-0.07_{syst}+/-0.01_{theor})x10;{-3}
  • EPI STAT, version 3.2.2.
  • Via Santa Marta n. 3 (address) and pH-stat
  • D Stat (author) and vol nr 3.

Thus it would be better to search for either merely

“stat3 transcription factor”[MeSH Terms]

or add synonyms (with OR) like stat-3[tiab], stat3[tiab], “stat 3″[tiab], “signal transducer and activator of transcription 3″[tiab].

This will increase precision and even recall.
However, one has to know how to find the correct terms and tags.

2. Citation Sensor

The renewed ATM was introduced together with the Citation Sensor that recognizes combinations of search terms characteristic of citation searching, e.g. volume nrs, author names, journal titles and publication dates, which it then matches to citations. These are shown separately in a yellow area above the retrieval.

Searching for limpens oncogene indeed suggests one paper of Limpens in Oncogene. This option can be very handy when one wants to retrieve a citation.

However typing: gene therapy 2007 405 gives 59 hits, but the citation sensor does not sense the specific paper in “Gene” year 2007, vol 405 (although retreived).

The Single Citation Mapper would have done better…. giving a single (correct) hit on both occasions.

Donna Berryman came to a very similar conclusion when writing to the MedLibList. She shows some other nice examples (i.e. that the citation sensor shows 4 citations from the journal Cancer by author Lung when searching lung cancer!!).

Donna explains that at the NLM booth at MLA, she was told that Pubmed changes were made to meet the wishes of a “significant” number of people that were going to PubMed, entering an author name and a journal title (with no field qualifiers) and expecting to retrieve a particular citation.

I’ve seen the nih.gov webmeeting presentation Donna referred to (click here)] as well as another (click here) (tips of the MedLib twitters @pfanderson and @eagledawg. Eagledawg (Nikki) also wrote 2 blogposts about this subject, see here (May) and here (June) )

It was quite revealing to see that empasis was given to numbers: number of visitors, numbers of queries versus number of documents and speed:

“if the query takes 2-3 minutes we loose users!”.

Well I can understand that NLM doesn’t want to discourage potential users, but I don’t understand why all functionalities have to be mixed in a way that it only serves the quick and dirty searches and even not very effectively. As Donna puts it: the new ATM is moving PubMed away from being a subject-based search. Again, most of my customers do subject searching.

3. Advanced search beta

Advanced search is a beta (version) and thus may be adapted based on findings and feedback (see here for announcement)

I don’t really know what to think of it. Firstly I wonder whether the Advanced Search is an extra option or meant to replace the present front page in due course. Secondly the Advanced Search looks quite complex, but not particularly advanced. The regular front page has more options (although hidden). This is certainly not an advanced tool for librarians, but is it an adequate tool for other users, clinicians or researchers?

Advanced Search beta consist of 5 separate “boxes”.

  1. The search-bar with a preview or a search option. Surprisingly the search option brings you back to the old front page. When you opt for “preview” you stay in the ‘advanced’ search.
  2. Search History showing the last 5 searches. If you exceed 5 searches a “More History” button appears. When clicked it brings up the full display.
  3. Seach by selected Fields. There are 3 default lines set up for Author, Journal and Publication date searching. Thus again, emphasis is given to reference instead of subject searching. Similar to the Single Citation Mapper, there is an auto-complete feature for authors and journals. On the right of each line is an index-feature.If you want to do a subject search (which in fact most advanced searchers do), you have to open the list of fields using the pull-down menu. However, for MeSH terms this is not ideal. Suppose you want to look up the MeSH for recurrent pregnancy loss (the term mostly used by clinicians). The MeSH is Abortion, Habitual. You won’t find the MeSH by looking at recur….. In effect, you won’t find it by looking up habit…. either. You have to start typing abortion…!?
    When you find an appropriate MeSH, you can choose to search for the MeSH coupled to a particular subheading (i.e. haemonchiasis/blood). You can see immediately how many hits will be retrieved (63).

    Suppose a clinician wants to know whether PGS is indicated in RPL. He pulls open the MeSH-field, types recurrent pregnancy loss, adds another MeSH-field and fills in preimplantation genetic screening, because he thinks PubMed will match it for him.


    He
    clicks a few limits because he thinks that might help to narrow his search, clicks the search button, waits and … ends up the regular front page showing zero results. So all steps he took didn’t lead him anywhere, because the appropriate MeSH (Abortion, Habitual and Preimplantation Diagnosis) weren’t found and he still has no clue as to what terms he should use.

    Even if the correct MeSH is found, the notation may be quite misleading. For example, after typing lung cancer into the box next to ‘Search MeSH terms’ , the History in PubMed will show lung cancer[MeSH Terms], whereas “lung cancer” is NOT the MeSH term. Thus people are going to think that lung cancer is the MeSH, because it looks like this. If they look in the Details box, however, they’ll see the real “lung neoplasms”[MeSH terms]. How are people going to know what’s what? (Thanks to Donna for providing this example).

    At least, in case of lung cancer, the correct MeSH-term is being searched. In contrast, a term like Lung embolism is not searched as Pulmonary embolism[mesh], and gives zero hits. Funny, because searching via the normal search bar would at least translate lung embolism in embolism[mesh] and lung[mesh]. (and there are several tricks whereby you can subsequently find the proper MeSH)


    Thus, in Advanced Search Beta, searching MeSH via ‘search MeSH-terms’ will only work when you know the (exact) MeSH-term in advance.

  4. The 4th box is really the limits-tab from the usual front page, but shown in full. A nice option is that you can lock certain limits while unlocking others (that is you can apply one limit to the next search and other limits to this and subsequent searches).
  5. The 5th box is (again) an Index of Fields. However it allows you to enter multiple terms.

In short, I’m not particularly impressed by this advanced search beta. It is too complex for a quick and dirty search as well as for a reference search. However, it is also not very well suited for an (advanced) subject search. It is not possible to look up any MeSH other than by index, and even this often goes wrong.
Some important functionalities are not included, like the clinical queries. Furthermore by displaying limits so prominently, many people will automatically use them. Personally I’m very reticent in using limits, because you miss non-indexed (i.e. recent) papers.

So I agree with tunaiskewl

“I stumbled across a beta Advanced Search in PubMed today. Has anyone else played with this? It appears that it merges the Preview/Index, History, Limits, and field searching screens all together in one place. Perhaps this will make some of PubMed’s features more obvious to searchers, but I’m not seeing too much benefit to it otherwise…”

4. Other minor recent changes include:

  • Create Collection in MyNCBI by one step via the send to option (this is wonderful!)
  • PubMedID (ID for Pubmed Central, at the bottom right)
  • Collaborators -display (separate from autors)
  • In Abstract Plus – (very popular with users, dynamic display format)
  • Blue side bar gone in certain display formats. Again this is done to make room for new functionalities (bad!, takes me 2 steps to go back to MeSH, Clinical Queries or whatsoever)

—————–

NL flag NL vlag

The Present: PubMed is going for the mass.

Dit is een vervolg op deel 1(zie hier)

Het lijkt erop dat enkele aanpassingen inmiddels doorgevoerd zijn, t.w.

1. Automatic Term Mapping (ATM).

Hoewel ATM een zeer ingrijpende verandering is, is de gebruiker hier nauwelijks van op de hoogte gesteld.

Ik kwam er bij toeval achter toen ik met een collega een keuzevak voor 2e jaars voorbereidde. Zoeken via de zoekbalk gaf heel andere resultaten, terwijl er uiterlijk aan PubMed niets te zien viel. De Details tab toonde een geheel afwijkende automatic term mapping, ook wel ATM of mapping genoemd. In PubMed’s “New and Noteworthy” werd dit wel aangekondigd, maar hoe velen lezen dit?

Men geeft hier het volgende voorbeeld:

Gene therapy wordt als volgt gemapt:

met de oude ATM: “gene therapy”[MeSH Terms] OR gene therapy[Text Word]

met de nieuwe ATM: “gene therapy”[MeSH Terms] OR (“gene”[All Fields] AND “therapy”[All Fields]) OR “gene therapy”[All Fields].

Dus de nieuwe ATM breidt de search uit:

1. door op All Fields te zoeken ipv. het tw-field (Titel, Abstract, MeSH)

2. door termen bestaande uit meerdere woorden op te hakken in de individuele woorden. Gene therapy wordt niet langer gezocht als “gene therapy”, maar als “gene” en “therapy”.

Volgens de NLM zoek je daarmee ook op synoniemen als “gene silencing therapy…” en vind je ook X in het auteursveld als je op X zoekt. Eigenlijk hadden ze moeten zeggen; ongeacht of je het wilt vinden. Dus van nu af aan zoek je automatisch in alle velden als je zelf geen tags toevoegt.

Of ik blij ben dat ik nu meer vind? Nou nee, ik gebruik de Single Citation Mapper wel als ik een citatie Y door auteur X wil vinden en ik breid searches liever uit door er relevante termen aan toe te voegen.
Dus hooguit zou ik gene silencing therap*[tiab] aan de search toevoegen, als ik heel breed wil zoeken. Dit breidt mijn search uit zonder onnodige ruis. Echter, goed beschouwd, is “gene therapy” (gentherapie, invoegen van een gen) toch wezenlijk anders dan gene-silencing (voorkomen dat een gen werkt door antisense oligo’s of siRNA). Daarom lijkt het me dit begrip voor de meeste searches over gentherapie niet echt bruikbaar. (Tussen 2 haakjes: er is een goede MeSH voor “Gene Silencing”, de nauwere term is RNA Interference)

Met gene therapy vindt ATM nu (5 juni) 90942 hits i.p.v. 36557, dus 54385 extra hits, dit is 2 ½ keer zoveel!!! De meeste van deze extra hits zijn niet relevant. Je vind nl ook citaties met therapy in ELK veld en:

  • gene als auteur : 53 extra hits
  • gene in het adresveld: hkj@gene.com of Department of Gene Regulation : 1327 extra hits
  • gene in de tijdschrifttitel, zoals “Gene” : 1487 extra hits
  • gene en therapy in het abstract/de MeSH zonder enig betekenisvolle relatie: artikelen over het effect van gene expression profiling op de prognose van borstkanker (na chemo, niet na gentherapie), studies over veranderingen in genregulatie na therapie X. De meerderheid van de extra hits zal onder deze noemer vallen.

Waarschijnlijk vinden meer mensen ‘deze enhancement’ niet prettig. De meeste gebruikers die ik ken zoeken op onderwerp en het grootste probleem dat ze hierbij ondervinden is dat ze teveel vinden wat niet relevant is (hoog number needed to read). ATM verergert dit alleen maar.

En wat te zeggen van:

  • mensen die zich van niets bewust zijn en de zoekbalk net zo gebruiken als vanouds
  • effect op bestaande alerts (RSS of MyNCBI)?
  • updates van eerdere searches, bijvoorbeeld voor een systematisch review. Ten gevolge van ATM vind je dan opeens na een bepaald tijdstip meer hits met dezelfde search (indien geen tags gebruikt)
  • het aanpassen van cursussen, tutorials, opdrachten, het PubMed boek dat mijn collega’s net hebben gemaakt? En wie zegt dat dit het einde is?

Van nu af aan zal ik (bijna) iedereen adviseren om niet langer maar via de zoekbalk te zoeken en slechts de Details te controleren, maar om de meest geschikte Mesh-term(en) te gebruiken en evt. op een of meer synoniemen in titel en abstract te zoeken.

D-dimer diagnosis lung embolism wordt volgens de huidige ATM vertaald als:

(“fibrin fragment D”[Substance Name] OR (“fibrin”[All Fields] AND “fragment”[All Fields] AND “D”[All Fields]) OR “fibrin fragment D”[All Fields] OR (“d”[All Fields] AND “dimer”[All Fields]) OR “d dimer”[All Fields]) AND (“diagnosis”[Subheading] OR “diagnosis”[All Fields] OR “diagnosis”[MeSH Terms]) AND (“lung”[MeSH Terms] OR “lung”[All Fields]) AND (“embolism”[MeSH Terms] OR “embolism”[All Fields])

Indrukwekkend niet, maar de meest geeigende MeSH, pulmonary embolism wordt niet gevonden!!!!

Is het dan goed voor de moleculair biologen e.a. preclinici? Stel dat je bijv. op zoek bent naar het eiwit signal transducer and activator of transcription 3. De meesten zoeken dan op het hele woord of stat 3, stat(3), stat-3 or stat3

1. stat 3 geeft: (“Stat”[Journal] OR “stat”[All Fields]) AND 3[All Fields] = 4031 hits

2. Stat-3 geeft: stat-3[All Fields] = 591 hits

3. stat3 geeft: “stat3 transcription factor”[MeSH Terms] OR (“stat3″[All Fields] AND “transcription”[All Fields] AND “factor”[All Fields]) OR “stat3 transcription factor”[All Fields] OR “stat3″[All Fields] = 4639 hits
(De grijze termen zijn dus eigenlijk overbodig want door op stat3 te zoeken vind je die al.

Niet erg consistent vertaald; alleen variatie 3 wordt gemapt met een MeSH, MAAR vindt evenals 1 geheel irrelevante hits als:

  • DeltaB=(1.18+/-0.09_{stat}+/-0.07_{syst}+/-0.01_{theor})x10;{-3}
  • EPI STAT, version 3.2.2.
  • Via Santa Marta n. 3 (address) and pH-stat
  • D Stat (author) and vol nr 3.

Daarom is het beter om of alleen op de MeSH te zoeken

“stat3 transcription factor”[MeSH Terms]

of om daar synoniemen aan toe te voegen als stat-3[tiab], stat3[tiab], “stat 3″[tiab], “signal transducer and activator of transcription 3″[tiab].

Hierdoor neemt de precisie en zelfs de recall toe. Maar je moet wel weten hoe de termen en tags te vinden.

2. Citation Sensor

Tegelijk met de nieuwe ATM werd ook de Citation Sensor ingevoerd. Deze herkent termen die karakteristiek zijn voor citaties. Als Citaties gevonden worden, worden ze apart in een geel vlak boven de zoekresultaten getoond.

Wanneer je op limpens oncogene zoekt zijn wordt het artikel van Limpens in Oncogene getoond. Deze optie kan handig zijn als je een citatie wil vinden.

Zoek je echter: gene therapy 2007 405 dan pikt de citation sensor niet het artikel in “Gene” 2007, vol 405 op temidden van de 57 hits.

De Single Citation Mapper zou dit beter gedaan hebben: 1 enkele goede hit in beide voorbeelden.

Donna Berryman kwam tot dezelfde conclusie in haar MedLibList-Mail. Ze geeft nog een paar andere leuke voorbeelden, zoals dat de citation sensor 4 citaties vindt van auteur Lung in het tijdschrift Cancer als je op lung cancer zoekt!!).

Donna vertelt dat ze op een NLM stand op de MLA hoorde dat er PubMed veranderingen doorgevoerd werden ten behoeve van een niet te verwaarlozen groot aantal mensen die alleen naar PubMed kwamen om een auteur of tijdschrifttitel in te voeren, omdat ze zo dachten een bepaald artikel te kunnen vinden

Hier is (waarschijnlijk) de webmeeting waar Donna aan refereert en hier een andere (tip van de MedLib twitters @pfanderson en @eagledawg. Eagledawg (Nikki) schreef, zo las ik later, ook 2 blogberichten over dit onderwerp, zie hier (Mei) en hier (Juni) )

Ik vond het nogal onthutsend dat getallen zo zwaar telden.

“if the query takes 2-3 minutes we loose users!”.

Ik begrijp natuurlijk wel dat de NLM ook degenen wil tegemoetkomen die alleen maar een artikeltje zoeken, maar moet dat ten koste gaan van andere functionaliteiten? Zelfs zoeken op een specifiek artikel verloopt niet altijd vlekkeloos. Het lijkt erop dat, zoals Donna het zegt, met de nieuwe ATM het zoeken op onderwerp minder belangrijk wordt. Nogmaals, de meeste mensen die ik ken zoeken op onderwerp.

3. Advanced search beta

Advanced search is een beta (versie), dus nog in de probeerfase. (zie hier).

Ik weet nog niet helemaal wat ik ervan moet denken. Komt het naast of in plaats van de oude entree? Ik het er nogal erg complex uitzien en toch niet erg geavanceerd. Niet alle opties van de normale openingspagina zijn aanwezig.

Er zijn 5 verschillende vakjes.

  1. De zoekbalk met een preview en een zoekoptie. Gek genoeg kom je als je op search klikt weer op de oude vertrouwde Pubmed pagina terecht. Als je daarentegen voor “preview” kiest blijf je wel in de ‘advanced’ search.
  2. Search History. Bij meer dan 5 searches moet je op “More History” klikken om de volledige zoekgeschiedenis te kunnen zien.
  3. Seach by selected Fields. Standaard kun je op Author, Journal and Publication date zoeken. Dus wederom erg gericht op het vinden van referenties. Handig is de auto-complete-functie voor auteurs en tijdschriften (net als in de Single Citation Mapper). Rechts is een aanklikbare index.Je kunt in andere velden zoeken door op het pull-down menu te klikken. Het is echter niet erg handig om zo op MeSH te zoeken. Stel dat je op recurrent pregnancy loss wil zoeken. De MeSH is Abortion, Habitual. Dat vindt je dus niet door op recur….. te zoeken in de index, en ook niet door op habit…. te zoeken.(in een update van de engelse versie heb ik een aantal voorbeelden toegevoegd die laten zien dat het zoeken van MeSH-termen via Advanced Serach beta niet goed verloopt, t.z.t zal ik die hier vertalen)

    Je kunt als je een MeSH vindt, deze alleen zoeken of met een subheading eraan gekopeld (bijv. haemonchiasis/blood). Het aantal hits (63) is direct te zien.

  4. Het 4e vak is eigenlijk de limit-tab, maar dan volledig getoond. Nieuw is dat je bepaalde limieten aan kan laten staan (locked), terwijl je andere alleen voor de volgende search gebruikt.
  5. Het 5e vak is weer een index van alle velden. je kunt hier wel verschillende termen tegelijk invoeren.

Samenvattend, ik ben niet bijzonder onder de indruk van deze ‘geavanceerde’ seach optie. het is te ingewikkeld en te weinig intuitief voor een snelle search of het opzoekwerk, maar het is ook niet erg geschikt voor een geavanceerde search. Met name omdat je de MeSH alleen via indexen kunt opzoeken. Ook zijn er minder opties. De Clinical Queries ontbreken bijvoorbeeld. Aan de andere kant zijn de Limits zo prominent aanwezig dat gebruikers misschien sneller dan normaal geneigd zijn ze toe te passen. Persoonlijk gebruik ik ze zeer beperkt!

4. Kleinere veranderingen

  • Je kunt een Collection in MyNCBI nu simpel aanmaken via de send to option (perfect!)
  • PubMedID (ID voor Pubmed Central, rechtsonderaan)
  • Collaborators -display (gescheiden van auteurs)
  • In Abstract Plus
  • De linker blauwe balk (met geavanceerde opties) wordt in bepaalde display formats niet meer getoond. Hierdoor zou er meer ruimte komen voor nieuwe functionaliteiten (als de related reviews), maar ik vind het heel vervelend omdat ik meer stappen nodig heb om na elke individuele zoekactie weer naar de MeSH of Clinical Queries terug te gaan.







PubMed: Past, Present And Future, PART I

11 06 2008

I.The Past:
Extremely simple, yet incredibly difficult

For Part II (discussion ATM, Advanced Search beta: see here).

Searching PubMed has never been easy, not for the advanced searcher nor the beginner.

As an advanced searcher you have (had?) to find your way through the Search Bar, MeSH-database, look for broader, narrower or related terms, know when to explode MeSH, add major topics or subheadings or not, know when to use ‘Links’ or the ‘Search to Sendbox’ to send Searches to PubMed. Know when and how to use Clinical Queries, Limits, Field Codes (nowadays called tags 🙂 ), History, MyNCBI saved searches and collections, linkouts, AND, OR, NOT and so on….

It takes some investment of time to become an effective & advanced PubMed searcher.

For the less experienced and/or more rushed people (busy clinicians, young investigators, lab-people) trying to find an answer to medical questions, the search bar often sufficed. Here you just typed in some words that were not only searched in title and abstract, but also translated into the corresponding MeSH (if recognized as synonyms), a process called automatic mapping. People just haved to check “Details” to verify proper mapping. It often went well, but sometimes the mapping was completely wrong (i.e. typ: walking aids and you will search for the MeSH term for AIDS, although HIV has nothing to do with it).

The overwhelming number of hits could be effectively reduced with some risk of loosing relevant hits by using the Limits option or using Methodological Filters in the Clinical Queries (EBM). Because of the disease-oriented MeSH, PubMed is not very well suited for preclinical or basic scientific searches. This often leads to frustrations (see below).

Some people just want to look up citations and there is a perfect tool for it: the Single Citation Mapper. It is so wonderful, just type in an author, the journal, first page or whatever. It has an autofill function, so I even prefer this tool to find a journal or an author (instead of the indexes, which is yet another option).

Now let alone the summing up of these possibilities makes me see stars. After a course PubMed a student who knew a lot about programming, sighed:

Wow, there is a lot of stuff in there, but it is all so concealed and difficult to find….”

That’s true, and this together with the superficial resemblance of the search bar with the Google search bar makes inexperienced users use PubMed in a Googlish way: just typ in some words ….. and you probably… don’t find what you want. This was especially true for people looking up a particular paper and not familiar with the Single Citation Mapper, hidden in the blue side bar. (The picture left is from “Arts in Spe”, with the Title: Searching like in Google”)

Or as the Harvard PhD student Anna Kushnir expressed her frustations when ranting against PubMed :

“I hate PubMed. I hate it with a burning passion. For a site that is as vital to scientific progress as PubMed is, their search engine is shamefully bad. It’s embarrassingly, frustratingly, painfully bad. (…)

… I can hold a paper in my hands, search for two authors’ last names and have PubMed come up with nothing. (….)

Why is PubMed so behind the times? Why? How does it even work? Does it search only the abstract? Does it also search the body of the papers that are available online? Why does it get so massively confused by an author’s initials and last name together, in one search. […]

I don’t think I should have to be, or enlist the services of, a medical librarian in order to do a simple search on a literature search engine. PubMed should be an intuitive search engine such as Google, or others. […] PubMed should be tuned to my needs and my skill set. I should not have to tune to it. […]”

There was an overwhelming response to her post and Anna’s story was covered in many blogs. I don’t want to revive that discussion, just want to mention Graham Steele’s comment.

“@ Anna,

You might just be in luck thanks to voicing your frustrations online !!

I brought this post to the attention of Dr Lipman who I’ve just heard back from.

He’s authorized me to post here on his behalf. (Thanks Dr Lipman)

Although the current engine works well for some users and some queries, I understand Anna’s frustration and we are in the midst of a number of changes that will make PubMed work better for her and many other users.

We will be adding a number of other “sensors” which will run in parallel with the default search. From monitoring results of enhancements we’ve added to some of our other Entrez databases.

A number of these complaints are fair and we’ll be doing our best to address them. With the large number of users we have, it will be clear what areas we’ll improving and what areas will need more work.”

I’m now beginning to understand what Graham Steel meant in his reply to Anna.

Coincidantly or not, PubMed has introduced a couple of changes that seem to concede Anna’s demands. This will be the subject of the second part of this Trilogy, see HERE

—————-

NL flag NL vlag

I.The Past:Extremely simple, yet incredibly difficult

Zoeken in PubMed is nooit makkelijk geweest, voor wie dan ook, beginner of gevorderde.

Als je echt volop gebruik wil maken van PubMed dan moet je niet alleen overweg kunnen met de zoekbalk, maar ook met de MeSH database. Je moet weten wat bredere en nauwere termen zijn, weten wanneer automatische explosie gewenst is of niet, wanneer je major topics gebruikt, subheading toevoegt en of je MeSH-termen via ‘Links’ of via de ‘Search to Sendbox’ naar PubMed ‘brengt’. Je moet weten of en hoe je Clinical Queries, Limits, Field Codes (tags), de History, MyNCBI saved searches and collections, linkouts, AND, OR, NOT enzovoorts, enzoverder gebruikt….

Het duurt dus even voor je alle ins en outs kent en op een effectieve manier van de geavanceerde mogelijkheden van PubMed gebruik maakt.

Voor de minder gevorderde gebruikers of de mensen die snel een antwoord willen op een (bio)medische vraag zoals artsen in de drukke klinische praktijk, fundamentele wetenschappers, preklinici voldeed vaak de zoekbalk. Je kon hier gewoon wat woorden intypen en ongezien zoekt (zocht) PubMed niet alleen in titel en abstract, maar vertaalde ze woorden ook in MeSH (als ze als synoniem herkend worden). Dit heet (automatic term) mapping of ATM. Makkelijk, maar het is wel aan te bevelen de “Details”-tab te bekijken om te zien of de search goed vertaald wordt. Soms gaat het namelijk helemaal fout. Bijv. als je walking aids typt, wordt o.a. op de MeSH voor de ziekte Aids gezocht, terwijl dat er natuurlijk niets mee van doen heeft.

Om de enorme hoeveelheid hits te reduceren kun je Limits of Methodologische Filters in de Clinical Queries (EBM-vragen) toepassen. Omdat de MeSH nogal georienteerd zijn op ziekten, is PubMed niet bij uitstek geschikt voor niet-medische vragen. Dit kan nog wel eens tot frustaties leiden. (zie onder)

Wanneer je alleen maar bepaalde artikelen wil opzoeken, kun je dat heel handig doen via de Single Citation Mapper. Typ gewoon de naam van een auteur, het tijdschrift, het pagina- of volumenummer, en/of een titelwoord in. En het artikel is zo gevonden.

Bij het opsommen van al deze mogelijkheden gaat het me al duizelen. Hoe moet het dan op beginners overkomen?

Na een PubMedcursus verzuchtte een student met veel ervaring in programmeren tegen mij.

“Wat een mogelijkheden, maar het is wel heel erg verborgen allemaal en erg moeilijk te vinden. Niet erg gebruikersvriendelijk.

Dat is zondermeer waar en omdat de PubMed zoekbalk oppervlakkig gezien wel op Google lijkt gaan onervaren zoekers (en met name de Google-generatie) erin zoeken als in Google. Ze typen de hele zoekstrategie gewoon in en verwachten dan snel wat te vinden. Helaas is dat niet zo. Zeker specifieke artikelen kon men zo vaak juist niet vinden, omdat wel automatisch met MeSH gemapt werd, maar meestal (juist niet) in het tijdschrift- of auteursveld gezocht werd. Daar was nu juist die handige Single Citation Mapper voor. Veel mensen kennen die echter niet, want de naam is nietszeggend en de optie zit in de blauwe zijbalk verscholen.

Ook promovenda Anna Kushnir liep hier tegenop en blies daarover stoom af op haar blog:

“I hate PubMed. I hate it with a burning passion. For a site that is as vital to scientific progress as PubMed is, their search engine is shamefully bad. It’s embarrassingly, frustratingly, painfully bad. (…)

… I can hold a paper in my hands, search for two authors’ last names and have PubMed come up with nothing. (….)

Why is PubMed so behind the times? Why? How does it even work? Does it search only the abstract? Does it also search the body of the papers that are available online? Why does it get so massively confused by an author’s initials and last name together, in one search. […]

I don’t think I should have to be, or enlist the services of, a medical librarian in order to do a simple search on a literature search engine. PubMed should be an intuitive search engine such as Google, or others. […] PubMed should be tuned to my needs and my skill set. I should not have to tune to it. […]”

Dit blog heeft heel wat losgemaakt, zowel onder voor- en tegenstanders. Ik zal nu niet het stof weer doen opwaaien, maar ik wil alleen nog even Graham Steele’s commentaar vermelden.

@ Anna,

You might just be in luck thanks to voicing your frustrations online !!

I brought this post to the attention of Dr Lipman who I’ve just heard back from.

He’s authorized me to post here on his behalf. (Thanks Dr Lipman)

Although the current engine works well for some users and some queries, I understand Anna’s frustration and we are in the midst of a number of changes that will make PubMed work better for her and many other users.

We will be adding a number of other “sensors” which will run in parallel with the default search. From monitoring results of enhancements we’ve added to some of our other Entrez databases.

A number of these complaints are fair and we’ll be doing our best to address them. With the large number of users we have, it will be clear what areas we’ll improving and what areas will need more work.

Ik begin nu een beetje te begrijpen wat Graham hiermee bedoelde.

Want toevalligerwijs of niet, zijn er enkele zaken ingrijpend veranderd in PubMed, veranderingen die Anna’s eisen lijken in te willigen.

Welke veranderingen dat zijn en wat voor een effect ze sorteren wordt in deel 2 van deze trilogie besproken, zie HIER





Not another howto… but whetherto!

10 05 2008

Liked this: “Not another 8 ways” post from “Levite Chronicles”

While reading another HOW-TO book he reflects that he would rather need WHETHER-TO books/guides.

“How do I decide whether to take those steps, to read that book, to read the blog that mentions the book, to write this post rather than clean off the desk or make the bed or just stop and think?”

His refers to another statement, which makes sense to me:

What separates the great innovator from the mere data gatherer is the ability to stop gathering data and think about what has been gathered.” (from **CrazyBusy: Overstretched, Overbooked, and About to Snap! Strategies for Handling Your Fast-Paced Life, by Dr Edward Hallowell, p 132.).

Yes, I do think I need a whether-filter. Do you?