User:Z3290841

From Embryology

-Z3290841 09:37, 30 July 2011 (EST)


Contents

Lab 1 Assessment

Identify the origin of In Vitro Fertilization (IVF) and the 2010 nobel prize winner associated with this technique

Origin of IVF

Studies and experiments about IVF have been going for more than a hundred years now. The first experiments and studies could date as far back as 1878, which involved the fertilisation of mammalian eggs in vitro, but were all unsuccessful. The source of this problem is the lack of knowledge about the need for egg cell maturation, sperm cell capacitation, and the correct media and condition for fertilisation. It was not until Austin and Chang coined and postulated sperm capacitaion that the technology produce more successful results.

Robert Edwards

He was the Nobel Prize laureate in 2010 in Physiology or Medicine for his contribution to the development of in vitro fertilisation. His work involved the development of a human culture media that allowed fertilisation and early embryo culture.


Identify a recent paper on fertilisation and describe its key findings

Terada Y, Hasegawa H, Ugajin T, Murakami T, Yaegashi N, Okamura K.(2009).Microtubule organization during human parthenogenesis.Fertility and Sterility, 91(4), 1271-2. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18706544

The key finding of the experiment that they did was the presence of multiple microtubule organising centre (MTOC) in human oocyte cytoplasm during parthenogenesis, which was previously only known to have been produced by the sperm centrosome in human fertilisation.


Identify 2 congenital anomalies

  • Arterial Septal Defect - type of congenital heart defect, whereby the blood flow between the left and right atria is through the interatrial septum
  • Spina Bifida - type of developmental congenital disorder, whereby there is an incomplete closing of the embryonic neural tube.


--Mark Hill 09:57, 3 August 2011 (EST) These answers are fine.

--z3290841 11:52, 4 August 2011 (EST)


Lab 2 Assessment

Identify the ZP protein that spermatozoa binds and how is this changed (altered) after fertilisation

Zona Pellucida Protein 3 (ZP3) is the glycoprotein where spermatozoa binds to, triggering an acrosome reaction that releases lytic enzymes, like acrosin and glycosidases. This aids in the movement of the sperm through Zona Pellucida. The ZP3 protein losses its ability to induce acrosome reaction and receive sperms once fertilisation occurs.


Identify a review and a research article related to your group topic

I did research on Cystic fibrosis and these are the 2 articles that I found that explains a lot about the disease, and the genetic research on it.


Review Article:

Cystic Fibrosis: Seminar

Description: This is basically outlining the pathophysiology of the disease, disease manifestation,current treatments diagnostic tool.

Ratjen F & Doring G.(2003).Cystic Fibrosis: Seminar.The Lancet, 361, 681-9. Retrieved from http://www.sciencedirect.com/science/article/pii/S0140673603125676


Research Article:

Gene expression profile study in CFTR mutated bronchial cell lines

Description: This article provides information about the severity of gene expression in relation of the extent or type of mutation.

Gambardella S, Biancolella M, D'Apice M, Amati F, Sangiuolo F, Farcomenti A, Chillemi G, Bueno S, Desideri A & Novelli G.(2006).Gene expression profile study in CFTR mutated bronchial cell lines.Clinical and Experimental Medicine , 6, 157-65. Retrieved from http://proquest.umi.com/pqdlink?Ver=1&Exp=08-05-2016&FMT=7&DID=1187181501&RQT=309&cfc=1


--z3290841 20:05, 10 August 2011 (EST)


--z3290841 11:10, 11 August 2011 (EST)

Differentially expressed RefSeq genes in human trisomy 21


Lab 3 Assessment

What is the maternal dietary requirement for late neural development

Iodine

Dietary Requirement = 0.22 mg daily

Food Source = Seafood and iodized salt

Role = Important in the production of maternal thyroid hormone, which is not only needed by the mother but also by the developing fetus. This is because of its role in neuronal migration and myelination. Lack of iodine, thus thyroid hormone, may lead to cretinism, which is a syndrome characterised by permanent brain damage and mental retardation.

For more information see: http://www.pronutrition.org/files/MaternalNutritionDietaryGuide.pdf

Omega-3 fatty acid DHA

Dietary Requirement > 300 mg daily

Food Source = pink salmon, white tuna

Role = an essential fatty acid that promotes neural stem cell differentiation into neurons. This is by prompting cell cycle exit and suppressing cell death

Folic Acid

Dietary Requirement = 0.4 mg daily

Food source = dark green leafy vegetables, breakfast cereals, beans (legumes), whole grains

Role = Consumption reduces the risk of infant neural tube defects because it is an essential component for producing follate which is needed in DNA synthesis.

Zinc

Dietary Requirement > 11 mg daily

Food Source = Organ meats, red meat, poultry, whole fish

Role = It is said to have a role in the absorption of folic acid, thus lack of it may also lead to neural tube defects.


Upload a picture relating to you group project

Tetralogy of Fallot

Right ventricle of heart with Tetralogy of Fallot.jpg

--z3290841 11:14, 15 August 2011 (EST)

--z3290841 12:59, 18 August 2011 (EST)

Lab 4 Assessment

The allantois, identified in the placental cord, is continuous with what anatomical structure

The allantois arises from the posterior part of the yolk sac. After the development of the hind-gut, around week 4-5, it is continuous with the cloaca, which is the terminal part of the hind-gut. It also moves closer to the umbilical vessels and becomes part of the umbilical cord.

Identify the 3 vascular shunts, and their location, in the embryonic circulation

  1. Ductus Venosus - connects the portal and umbilical veins to the inferior vena cava
  2. Ductus Arteriosus - connects pulmonary trunk to aorta
  3. Foramen Ovale - connects right and left atrium

Identify the Group project sub-section that you will be researching

  • Introduction
  • History
  • Epidemiology
  • Signs and Symptoms
  • Genetics/Aetiology
  • Pathophysiology and Abnormalities
  • Diagnostic Tests
  • Treatment/Management
  • Prognosis
  • Future Directions
  • References

--z3290841 08:40, 24 August 2011 (EST)

--z3290841 12:49, 25 August 2011 (EST)

Lab 5 Assessment

Which side (L/R) is most common for diaphragmatic hernia and why

One of the developmental abnormalities of the diaphragm is Congenital Diaphragmatic Hernia (CDH), and a left sided Bochdalek hernia is the most common type of the abnormality. This means that the herniation occurs at the postero-lateral area of the diaphragm. The early closure of the right pluroperitoneal opening might be the cause as to why a left-sided CDH is more common.

--z3290841 08:20, 1 September 2011 (EST)

--z3290841 11:22, 1 September 2011 (EST)

Lab 6 Assessment

What week of development do the palatal shelves fuse

The palatal shelves fuse during the 9th Week of embryonic development. This involves the growth, elevation and fusion of primary palate, and then fusion with the secondary palate[1].

What early animal model helped elucidate the neural crest origin and migration of neural crest cells

The quail-chick chimera was the early animal model used by Nicole Le Douarin to elucidate this. This is by grafting a neural crest tube and cells in the host chick's embryo. This is because Le Dourin have identified that a stain called the Fuelgen stain is ale to distinguish the cell form quail and chick[2].

What abnormality results from neural crest not migrating into the cardiac outflow tract

Some of these abnormalities include:

  • Persistent Truncus Arteriosus (PTA)
  • Double outlet right ventricle (DORV)
  • Dextraposed aorta (DA)
  • Tetralogy of Fallot (TOF)
  • Ventricle septum defect (VSD)

Eperiments on mouse showed that partial ablation of cardiac neural crest results to DORV, DA, TOF and VSD, while PTA is the result of complete ablation of cardiac neural crest[3].

--z3290841 08:21, 15 September 2011 (EST)

--z3290841 11:08, 15 September 2011 (EST)

Lab 7 Assessment

Are satellite cells (a) necessary for muscle hypertrophy and (b) generally involved in hypertrophy

According to studies on satellite cells, they are not necessary for muscle hypertrophy, but they still undergo hypertrophy. This is why in the experimental studies of skeletal muscle the results showed that the muscle being studied underwent hypertrophy even though satellite cells have been deactivated. At the same time in another experiment where satellite cells haven't been deactivated, the muscle cells have increased in number, which is double the amount compared to when satellite cells are deactivated. This illustrates the ability of satellite cells to hypertrophy.

Why does chronic low frequency stimulation cause a fast to slow fibre type shift

Chronic low frequency stimulation mimics the slow electrical signalling of motor neurons. Slow fibre muscles are more sensitive and responsive to these types of signals. Studies conducted investigating types of muscle fibres and conversion of the fibres to different types illustrated that these electrical stimulation/signals have the ability to transform/convert fast muscle fibres to slow muscle fibres. This is because chronic stimulation of fast fibres by low frequency signals activates an adaptive response that converts the muscle fibre, but the conversion follows the "next neighbour" rule, whereby the muscle fibres get converted in stages from a fast muscle fibre type to a slow muscle fibre type. It follows the following sequence of fibre types, from fastest to slowest type:

  • IIb
  • IIx
  • IIa
  • I

Also note that it could go from slow to fast fibres as well.

Trisomy 21 page Evaluation

Good brief and concise introduction. The use of the links at the end of the introduction is very helpful as the reader doesn't have to go back and fort if a section for external links was just made, but I believe there are too many links to put in one section, especially the introduction, it makes the section too cluttered and busy. I believe some of the links could be reevaluated and see if they should be incorporated in the page/section.

The recent findings section was an amazing idea, as it allows the reader to see that there are current progress on the disease, and it also gives credibility to the page as being up-to-date with the information.

I believe the karyotyping, aneuploidy, and Meiosis 1 & 2 section can be combined together as 1 subheading talking about the genetics/aetiology of the disease, which is not really explored in the page. It would have been much more informative if the page discussed about the current theories as to how the aneuploidy occurred, and use the Meiosis 1 & 2 section as back up evidence for it. Basically some of the sections are informative but not really necessary, like the Aneuploidy section, and it would have been better if the genetics side of things have been further explored.

The associated congenital abnormalities, heart defect and limb defect could have been synthesised together and presented in a much more conducive way, where the information is organised in a more orderly fashion, like the use of subheadings. The information contained in each of the 3 sections mentioned above have enough detail to get an idea about the defects in the disorder.

The section American College of Obstetricians and Gynecologists Recommendations and Trisomy growth charts could be interchanged, as it may allow the page to flow better than how it is.

The section of Prevalence and Diagnosis are done very well and are very informative.

The images and diagrams are used effectively throughout the whole page, there are no diagrams that should not be found in a section that it should not be in.

Overall it is a good page, not outstanding. It could still use some more information in it and the structuring could still be modified.

--z3290841 08:33, 22 September 2011 (EST) --z3290841 11:58, 22 September 2011 (EST)

Peer review:

Group 1

  • The introduction is good because it is brief and concise. Although it would have been good if the page actually introduced the headings that you guys have. It just allows the reader to find out what to expect on your page and if they need particular information they could just jump to that section. Also it didn’t really specify that the disease is a female only disease.
  • The epidemiology section is fine and it lists the general occurrence of the disease. The graph used in the section is very effective in illustrating the observable malformations in the population. If there are more information about the demographics of the disease it would make this section better than what it is already. Some of the criticisms on this section are the use of the karyotyping image. I think the image is a bit out of place and should be placed in another section, and lastly it would also be helpful if some of the terms are defined within the section. The glossary section is good and all but, it just makes reading the page a bit more disjointed. I think the flow of the whole page would be better if the explanations of the terms are done immediately.
  • The etiology section is straight to the point, descriptive and informative as well. The images are used effectively and they relate back to the information given. Only a criticism is the grammar of the section, it could be improved further. For example “When an uneven distribution is such that one of the gametes does not have any of a chromosome…” it doesn’t really flow or make sense. Also if the structuring of the whole section can just be revised a bit and clean up it would be near perfect.
  • The clinical manifestation section is too much of a list; it is not very informative or descriptive at all. Even though each characteristics of the disease were referenced very well and the reader can immediately follow the link as to where more information could be found, it would probably have been preferable if at least the main clinical manifestations were defined and described here and explain how it is actually presented in the patient. Also an image in this section would not hurt.
  • The diagnostic procedure of the page is done pretty well especially the table. The table was very effective and it summarized the basic diagnostic tools needed in the section. My only criticism for this section is that the very last sentence is a bit confusing, if you could just fix that up a bit. There are a lot of concepts being introduced in one paragraph that it becomes very confusing.
  • Treatment section didn’t live up to its name unfortunately. Although there is one subsection (puberty and growth) that was very informative of the actual treatment for the disease, the rest are not very helpful at all. I guess some more research needs to be done for this section of the page.
  • I really like the research part of the page because it tells you that your page is up-to-date and that your research is up-to-date as well. It gives the reader a sense of security that the data used are not old. The use of future research is also a great idea, although would have love to see some of the page creator’s own opinion about the future direction of this page, as it allows the reader to see that the creators of the page are also being critical of the disease.
  • I am not really a big fan of glossaries. Although it is good that you guys incorporated that in the page, I personally am not a big fan of it as it makes the reading of the page a bit disjointed. If it is possible to avoid going to the glossary and just explain some of the words in context, I believe it will make the page much better.

Group 2

  • The introduction is done quite well. It is succinct and brief. You have done a very good introduction to the topics that your page is about to explore. Unfortunately you did fail to introduce some of the headings that your page have, like the diagnostic section. Aside from this it is a good introduction overall.
  • Historical background is done very well. It has enough detail to see the ongoing achievements on the disease.
  • The epidemiology was excellent. You have covered the demography of the disease and properly cited some of the facts that you try to get across. Revision of some of the sentences may be needed because some sentences are not expressed properly. Also it would have been really nice if you could incorporate some of the data that was mentioned in a more summarized form, like a table, dot points, or something. It just makes reading easier and less likely to get lost in the words
  • I really like how concise yet very informative your etiology section. What would make this section better than what it is at the moment is an image that would complement the information, and also a bit of an explanation about some of the terms that is in there, like “hemizygous”.
  • The Pathogenesis section is very well done. It contains enough detail that we get an in-depth knowledge about the development of the disease, and the images that were used are very helpful. One thing that would improve it though is that if you can elaborate further on the function of the TBX1 gene and how affecting the expression of this gene results to DiGeorge.
  • The Diagnostic test section I think is perfect. The way the test works was described, and at the same time they were all related back to how this aids in the detection of the disease. The layout of the information is also very engaging.
  • Clinical manifestation is very nicely done. The information was very descriptive and informative. It is also presented very well. Just one thing though is that there is no clear separation between two clinical outcomes, so it tends to get confusing sometimes when someone is reading it. I guess adding more space between would be a good idea.
  • Treatments section is done quite well. If you could add a video of some of these treatments or even just a link to a video of it that would really make this section perfect.
  • The research section is also very good, especially your insight to future direction of research on this disease. I guess it wouldn’t hurt to drop some current research articles within this section, which shows the readers that the information that they have just read is up-to-date.
  • Glossary is a good idea, not really a big fan of it but good idea anyway.

Group 3

  • The introduction is good. It brief and informative of what t o expect in the page. The only criticism I have is that the historical background that was placed towards the end of the section, which should probably have been in the beginning or incorporated somewhere there.
  • The History section is good, but probably too detailed. I think you can mix the timeline and history together and make this section a bit more concise.
  • Epidemiology is a bit of a disappointment for me. There is a bit of information of the demographics of the disease, like prevalence, but I think epidemiology should go deeper into it, like talking about geographical distribution or if there is any race that are more inclined to developing the syndrome. Also this section ended up being an in-depth illustration of a patient’s clinical manifestation. Probably a few statistics on what percentage shows these different types of manifestation and figures some figures of the variation in mutation.
  • The etiology section is very informative and I think it has all the information needed for that section. I just think that the arrangement of the information could probably be changed a bit. I think the genetics subsection is unnecessary, even though it does break the section up a bit and allows categorization of it. I just think that you could organise the ideas in this section better than what it already is. The image used here was very appropriate and aids the reader.
  • I really like your pathogenesis section. It’s simple yet informative. It is very effective because the terms and concepts that you guys have here are not foreign to the reader because you have already introduced them beforehand, or explained it. Only downfall I guess is the referencing. There is only one section of your information that is referenced.
  • Signs and symptoms are done well. You got away with just listing them because most of it is self-explanatory. I guess the only thing that will make this section amazing are some more elaborate images.
  • Diagnosis section is done quite well, although the heading should be reconsidered to something like diagnostic test/procedure or something because the diagnosis is “klinefelter’s syndrome”. You also did a good job in incorporating what the tests are looking for, especially in the karyotyping bit. Unfortunately, this was not done for prenatal diagnosis methods, so a bit more information on this one. Finally, I don’t think the statistics need a whole subheading for it. It could just be part of an introduction to this section.
  • I like the management section and the image that you used with it is used appropriately and very useful
  • The other similar defects is informative, but I think that you went into far too much detail for it in a page dedicated for klinefelter’s syndrome. It is written well and the information in it are amazing though.
  • I like the current research section because it says to the reader that the information on this page are up-to-date, giving the whole page credibility. What would probably make it better is a future direction kind of area, where you can put in some proposed theories or studies by researchers, and at the same time some of your own ideas of the direction where this syndrome should head into.
  • I am not a big fan of glossaries, but it does look good

Group 4

  • The introduction is very informative and actually introduced most of the subheadings that will be discussed in the page. The downfall of this introduction is the failure to introduce all of the sections of and proof-reading this section it is fine.
  • The history of the disease is very well-done. The quick description or beginning of the history combined with the timeline is utilised well. Only improvement that would make it better is making the dates stand out by putting it I bold or something.
  • I can find no fault in the epidemiology. It is the best one I have seen so far. You have described the demography of the disease and the statistics of other mutations. The tables were used appropriately as well, and the fact that it was described straight after the table is perfect.
  • I like the genetics section of the page. It made sense and easy to understand. The diagrams are all relevant to the page section. Only criticism I can say is the description of the gene could probably be organised in a much simpler or better fashion, like a table, rather than just one whole sentence. Also I don’t know if it is typo or if that’s how you actually spell it, but I would just like to mention “Huntingtin gene”.
  • The pathogenesis section is very informative of the disease. Unfortunately it is very disjointed. One idea was introduced after the other and they did not really connect properly. I think as the reader I am looking for some sort of direction that leads Huntington’s, like a step by step thing.
  • I am assuming that the clinical manifestation is not yet finished, so I won’t say anything else other than change the positioning of the image to the other side because it breaks the page and it does not aid in getting the information across to your readers.
  • The diagnostic test is a bit of a disappointment. I’m pretty sure that since it is a genetic disease there is some form of genetic testing that doctors can use to diagnose the onset of the disease, unless the etiology is still under debate and not sure of, and from what I have read from your page so far it is pretty definite that mutation in a particular gene is already implicated in the disease. So I think this section could probably do a lot more research and work.
  • The video… section of your page is pointless, why isn’t this in the diagnostic section?? I think synthesizing both section is needed, as this section alone is pointless.
  • The really like the table in the treatment section it is a a very good summary. If you could add the actual effect of each drugs to the patient, it would make this table better than what it actually is. The tetrabenzaine part is a bit out of place. If you are elaborating on the entire active chemical ingredients, I believe this is a good idea.
  • I like the current and future research section of the page, as it informs the reader that the page is current and well informed about the recent endeavors on the disease. The only let down is that there is not a single research on finding a cure for the disease or looking for other treatments, which I think is one of the most popular topic on this disease. If you could add this in this section it would make this area much better. You could even add it in the treatment section.
  • Not really a big fan of the glossary, but it is good idea anyway.

Group 5

  • The information in the introduction is good but it is way too brief. The other section of the page was not introduced or not introduced properly, like the diagnosis section. Adding these bits would probably make the introduction good and a bit more informative as to what to expect from the page. Also reference them.
  • The history I think is fine the way it is.
  • The epidemiology is good because you have touched upon the demography of the disease and its prevalence. It would have been better if you could add a bit more statistics on the geographical distribution of the disease, as it makes the section more credible than how it already is. Unfortunately I think the section from “Screening… “ onwards is not very relevant for this section. I would consider revising as to where this information should be placed under. I guess this section needs more research overall.
  • The etiology is very informative and I think you have gone in-depth in the topic, and is well researched, but I think it needs some revision. The concepts were far too technical and it makes the reader a bit too confused about what the information is actually saying. The images are amazing, and if you could incorporate them in the text it would make the section better.
  • The development of the disease section I think should be the pathogenesis of the disease. This section was not done properly, as I was expecting to see how the etiology and all the clinical manifestations relate to each other; instead it was all about the clinical manifestation. I think you need to look further into this section.
  • The signs and symptoms section is very informative, but I am questioning the information as it is not referenced at all in most of the paragraph.
  • Diagnosis should probably changed to diagnostic tests because the diagnosis is Fragile X. The information is good for introducing the techniques to the reader. I think further description of the tests is needed.

The treatment section has some very good information on it that describes the treatments used for the disease. It could probably be better if you could highlight the actual treatments and make it stand out.

  • Recent research is a bit disappointing because the most recent research that were presented is 3 years ago. As a reader, this makes me question the content of the page, whether it is up-to-date or not. It would also be good to have a more recent paper/research and the inclusion of future direction of this disease.

Group 7

  • Introduction is too brief. It would be good if you could introduce the other headings that you guys have in your page.

History is informative and the timeline is a good summary of the history. It could be improved by adding an image of Dr angelman or something relevant to the section, also it you could make the dates in the timeline stand out more.

  • I like the simplicity of the epidemiology. The use of an image would probably make this section better. Also if you could add a bit more statistics to this part, it would be more informative.
  • Aetiology is not informative enough. I think you need to further research this section and add a bit more information about the mutations, and the table doesn’t really make a lot of sense as well.
  • I really like the pathogenesis section. It is very informative and fully explains the disease process. The diagram that was used is very useful in understanding the disease process. Only criticism is that sometimes the paragraphs get out of hand and goes to verbose for the reader to understand. If you could elaborate further on the technical concepts it would help a lot.
  • Fix up the heading. The table is a bit confusing when you first look at it. Aside from these 2 the information I think covers the idea of the signs and symptoms of the disease.
  • I think the heading should be Diagnostic tests because the diagnosis is Angelman Syndrome. The flow diagram is good for this section and the information provided are all relevant. Just make sure to make the little headings bold and not italics, and not dot points as it makes it better.
  • Treatment is summarized perfectly . I just think that you should make the left column bold.
  • The genetic counseling section doesn’t make sense to me. I think you should at least have some description of this section and explain what it is for
  • The current and future research could be further improved by actually mentioning current research being done (article names), and a future direction reflection would probably be good as well.

--z3290841 10:25, 29 September 2011 (EST)


attendance --z3290841 11:21, 6 October 2011 (EST)

Lab 10 Assessment

Besides fetal alcohol syndrome, identify another environmental teratogen that can lead to hearing loss

Thalidomide is an environmental teratogen that can be found in drugs that control nausea in the 1950s and was banned in 1961 because of all the birth defects that is associated with the drug. This includes hearing loss or the lack of development of the ear.

Identify 3 factors that contribute to poor neonatal drainage of the middle ear

The three factors that contribute to poor neonatal drainage of the middle ear includes:

  • Size of the Eustachian tube
  • Orientation of the Eustachian tube
  • Muscles that opens up the Eustachian tube = only one in neonates (tensor palati) compared the 2 muscles in adult (tensor palati and levator palati)

Identify 1 genetic abnormality that affects hearing development and link to the OMIM record

One genetic abnormality would be in DIAPH1 gene of chromosome 5. This leads to Hereditary Low Frequency Hearing Loss. OMIM number 602121


Attendance lab 10: --z3290841 12:48, 13 October 2011 (EST)

Lab 11 Online Assessment

Name the components that give rise to the interatrial septum and the passages that connect the right and left atria

  • Septum primum
  • Septum Secundum
  • Foramen secundum
  • Foramen ovale

Identify the cardiac defects that arise through abnormal development of the outflow tract

  • Tetralogy of Fallot
  • Transposition of the Great Vessels
  • Hypoplastic Left Heart Syndrome
  • Double Outlet Right Ventricle

--z3290841 10:56, 20 October 2011 (EST)

Attendance: --z3290841 12:03, 20 October 2011 (EST)

Lab 12 Online Assessment

Give examples of 3 systems that continue to develop postnatally

  • Central Nervous System - brain development
  • Respiratory System - breathing mechanism (ribs orientation)
  • Musculoskeletal system - bones still undergoing ossification, and also muscular development.

Identify the abnormalities detected by the Guthrie Test and link to one abnormality listed in OMIM

  • Phenylketonuria (PKU)
  • Hypothyroidism
  • Cystic Fibrosis - OMIM number: 602421
  • http://embryology.med.unsw.edu.au/embryology/index.php?title=Palate_Development
  • http://www.sdbonline.org/archive/dbcinema/ledouarin/ledouarin.html
  • http://cardiovascres.oxfordjournals.org/content/47/2/212.full