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Excerpt for Vaccine Science Revisited: Are Childhood Immunizations As Safe As Claimed?:


MMR, the viral riot

“Love is like the measles; we all have to go through it.” –Jerome K. Jerome (English writer and humorist)


Measles, mumps and rubella viruses cause acute infections that are dependent on humans for survival and replication.

The measles virus enters your body as you inhale. When inhaled through the respiratory tract it multiplies silently in the tissues for a week then goes into the lymph nodes and eventually enters the bloodstream. The body fights hard to produce antibodies and once it overcomes the illness, you are immune for life.

Some people say measles is a deadly disease. Perhaps it is if you live in poverty and have poor nutrition, poor sanitation and a contaminated water supply. In that case, any germ can be deadly. As long as you live under clean conditions, measles should not be a virus of much concern.

Measles virus has the ability to suppress the immune system and it’s common to get secondary infections like ear infection. These secondary infections are usually treated successfully with antibiotics.

As with measles, the mumps virus is one of those viruses best contracted during childhood. When adult men get mumps, it can cause orchitis, which is an inflammation of the testicles and has been associated with infertility.

Rubella is normally a rather mild disease. It has been considered a typical childhood disease throughout history, but turns into a very serious disease for a pregnant woman when she becomes infected. If the virus spreads to the fetus, it can cause a spontaneous abortion and severely disturb the fetal developmental process which is known as congenital rubella syndrome (CRS).

A large study conducted in Japan discovered that those who had measles and mumps during childhood were significantly less likely to die from heart attacks and strokes later in life. Another study showed that for each additional childhood illness, such as measles, mumps or rubella, the less likely the person was to suffer acute coronary events.


The first defenders

As you may remember, our innate immune system (first responders) does not work with antibodies. It works mostly with something called natural killer (NK) cells and is often vitamin D dependent. Our innate immunity is the most important immune defense we have.

We know that people with antibodies to specific diseases may still succumb to those diseases. We also know when you have a community-acquired infection, such as measles or mumps, it engages both sides of the immune system. The Th2 cells create the antibodies and the Th1 cells are defined by knowing the difference between you and foreign substances that are not a part of you. It is also known that certain viruses, such as the measles virus, powerfully suppress immunity.

A study done in Faroe Islands showed that once somebody became sick with the measles, they stayed immune to that disease for 75 years. Those who were vaccinated against measles only had immunity lasting for about 20 years. This means if vaccinated in childhood, a woman is unlikely to pass the immunity on to her baby or at least pass it on as effectively as she would have had she contracted measles naturally.

It’s essential for our immune system to develop and grow by facing natural infectious challenges.

If the body is deprived of the opportunity to fight natural infections, the immune system won’t gain the required strength or knowledge to fight on its own. As a consequence, a range of hidden conditions that adversely affect your immunity may be expressed. These conditions are sometimes called Th2 dominant disorders. This happens when our immune system is not challenged by normal infections or bacteria in the environment.

Our body’s microbiome is primarily bacteria, viruses, and fungi. We need these naturally acquired infections to help stimulate our immune system so our body as a whole becomes stronger and keeps us healthy.


The vaccine kitchen

When preparing the chicken embryo agar to grow the viruses, scientists first incubate chicken eggs for 16 hours. (An agar being a natural gelatinous substance used in biological culture media). The shell is then cracked and the albumin removed. An albumin-saline solution is transferred to a Falcon culture dish.

In the MMRII vaccine, the measles and mumps virus are propagated in chicken embryo, while Rubella virus is propagated in WI-38. After these have been propagated separately, they are then combined into one vaccine. The final product will therefore not only have all three viruses, but also chicken embryo proteins from two separate cultures and human proteins. The ProQuad vaccine has the added varicella virus, which was propagated in MRC-5 cells before being combined into one vaccine.

In Japan medical authorities took the Urabe AM9 mumps vaccine and gave five million doses in a single vaccine. There were few, if any, reported cases of meningitis related to the vaccine. When they combined measles, mumps and rubella, there was a dramatic increase in the adverse reactions to the mumps virus in the vaccine, mostly in the form of meningitis.

Unsurprisingly, after that scandal the Japanese authorities took the MMR vaccine off the list of recommended vaccines. Their experience was that when you combine three viruses into one, you’ve got major problems.
The same thing happened in Bulgaria where they used a mumps strain called Sofia 6. The strain appeared to be triggering cases of meningitis, so it was discontinued.

According to the History of Vaccines website, Stanley Plotkin, a scientist who invented the rubella vaccine, grew the rubella virus he had isolated in WI-38 cells that were kept at 86°F (30°C). Plotkin did this to force the virus to adjust to the warm temperature so that it would grow very poorly at normal body temperature. He grew the virus “through the cells 25 times” and after that, “it was no longer able to replicate enough to cause illness in a living person.” It was, nonetheless, still able to provoke a protective immune response.

The article then states:

“Rubella vaccine developed with WI-38 is still used throughout much of the world today as part of the combined MMR (measles, mumps, and rubella) vaccine.”

So, in the US we have the RA273 strain, and in Japan the Takahashi strain. The Americans grew their cells on the aborted fetal cell line WI-38, and the Japanese grew theirs on a rabbit cell line.

The NIH rubella vaccine was captured from the throat of a soldier in 1961 and then grown in African green monkey kidney cells that did not harbor the SV40 virus. A Missouri-based company, Phillips-Roxanne, grew the virus in pup kidney cells, and in Belgium a company captured the virus from the urine of a sick 10-year-old girl and grew it in rabbit kidney cells.

Three vaccines were approved in 1969 and none of them used human cells. They all used animal cells and they all eventually disappeared from the market after Plotkin’s vaccine was finally approved in 1979. The Philips-Roxanne vaccine only lasted six to nine months on the market because once it was used in a bigger population it was found to cause bad side-effects in kids, triggering very sore knees caused by inflammation.

A study was done to see how much aborted fetal DNA was in the vaccines. The author studied a rubella vaccine called Meruvax II, manufactured by Merck, for ssDNA and dsDNA. The average ssDNA was 142.05 ng and the average dsDNA was 35.00 ng. If you recall early in this book we mention the FDA safety guidelines specify the amount of residual DNA should be no greater than 10 ng.

Recently, information was released that the ProQuid combination vaccine by Merck resulted in twice as many seizures when the vaccines are dispensed separately.

If guidelines are ignored, seizures can and do result.

MMR is the only vaccine that contains more than one live vaccine in one shot. This one contains three, which is why some believe the vaccine is a problem. All these viruses are swimming around together in the vial and they could interact and mutate in ways we might not have foreseen.

As mentioned above, Japan withdrew its home-produced MMR vaccine in 1993 after around 1,000 children suffered side-effects, in particular aseptic meningitis. The problem was pinned on the mumps component produced in Japan, which continued to vaccinate against measles and rubella using single vaccines.


Everyone gets vaccinated

According to WHO data, there were 16 African countries that exceeded the United States’ vaccination rate of 91% for the measles-mumps-rubella vaccine in 2013.

Besides those African countries, many other parts of the world have outperformed the US in giving infants the MMR vaccine at their one-year immunization. These include Australia, China, New Zealand and most of the European countries.

In 2017, the WHO recorded that 92% of the US population received their first dose of the measles vaccine at age one. There are countries, such as China, Cuba and Thailand that achieved as much as 99% coverage dispensing first measles vaccine dosages.

There is now no country in the world that offers single vaccines in preference to MMR. Therefore, the measles vaccine can be considered to be a three-in-one measles-mumps-rubella vaccine (and not just a measles vaccine).


Autism

The MMR vaccine has been notoriously and infamously correlated with autism, the early childhood mental condition that is increasing so drastically the Autism Society of America considers it (autism) an epidemic.

To be more specific, this correlation between the MMR vaccine and autism is linked with the measles component of the MMR vaccine. One study showed:

“[…] over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism.”

This is saying that over 90% of the blood samples in the study had antibodies from the MMR vaccine and also autoantibodies for myelin basic protein (MBP). This protein is found in the myelin sheath covering our nerves. When a person suffers from a disease that destroys the myelin sheath, MBP can be found in the blood.

When you take three live viruses and inject them into a child in a way human evolution has never seen before, the game changes and all bets are off. The outcome is simply unknown.

Viruses have been known to attack our nerves. An example of such a viral attack would be shingles. So, it should be of no surprise that when a variety of ingredients in a vaccine known to affect the nervous system is combined with three living viruses, they have the ability to destroy not only the nerves themselves, but also destroy their means of travel throughout the body.

More on the MMR vaccine and autism in the following chapter.

Chapter 39: MMR, the viral riot:

Kubota, Y., Iso, H., Tamakoshi, A., and JACC Study Group. (2015). Association of measles and mumps with cardiovascular disease: The Japan Collaborative Cohort (JACC) study. Atherosclerosis, 241(2), 682-686.
Pesonen, E., Andsberg, E., Ohlin, H., Puolakkainen, M., Rautelin, H., Sama, S., and Persson, K. (2007). Dual role of infections as risk factors for coronary heart disease. Atherosclerosis, 192(2), 370-375
Kerdile, Y.M., Sellin, C.I., Druelle, J., and Horvat, B. (2006). Immunosuppression by measles virus: role of viral proteins. Rev Med Virol, 16(1), 49-63
Corning. (2007). Falcon Product Selection Guide. Retrieved from https://www.corning.com/media/worldwi...
World Health Organization (WHO). (n.d.). M-M-R II. Retrieved from http://www.who.int/immunization_stand...
Food and Drug Administration (FDA). (n.d.). ProQuad. Retrieved from https://www.fda.gov/downloads/biologi...
Tanaka, Y., Ueda, Y., Yoshino, K., & Kimura, T. (2017). History repeats itself in Japan: Failure to learn from rubella epidemic leads to failure to provide the HPV vaccine. Human vaccines & immunotherapeutics, 13(8), 1859-1860.
Odisseev, H.1. and Gacheva, N. (1994). Vaccinoprophylaxis of mumps using mumps vaccine, strain Sofia 6, in Bulgaria. Vaccine, 12(14), 1251-1254
The College of Physicians of Philadelphia. (2018, January 19). Human Cell Strains in Vaccine Development, Retrieved from https://www.historyofvaccines.org/con...
Ibid.
Deisher, T.A., Doan, N.V., Koyama, K., and Bwabye, S. (2015). Epidemiologic and Molecular Relationship Between Vaccine Manufacture and Autism Spectrum Disorder Prevalence. Issues Law Med, 30(1), 47-70.
The World Bank. (2018). Countries and Economies. Retrieved from https://data.worldbank.org/country
World Health Organization (WHO). (2018, July 19). Global Health Observatory data repository. Retrieved from http://apps.who.int/gho/data/node.mai...
The Washingtom Post. (2015, February 3). Map: 113 countries have higher measles immunization rates than the U.S. for 1-year-olds. Retrieved from https://www.washingtonpost.com/news/w...
https://www.npr.org/sections/goatsand...
Singh, V.K., Lin, S.X., Newell, E., and Nelson, C. (2002) Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism. J Biomed Sci, 9(4), 359-364.
Mondello, S. and Hayes, R. (2015). Chapter 16 –Biomarkers. Traumatic Brain Injury [Vol.1, Part 1, pp. 245-265]. Waltham, MA: Elsevier B.V

Excerpts from Chapter 40 in Vaccine Science Revisited: Are Childhood Immunizations As Safe As Claimed?:


MMR – Autism and a ravaged immune system

“A further sign of health is that we don't become undone by fear and trembling, but we take it as a message that it's time to stop struggling and look directly at what's threatening us.” ― Pema Chödrön (The Places that Scare You)


The FDA warns that all drugs containing human albumin could result in prion or viral disease contamination. It’s worth noting the MMR vaccines contain genetically engineered human albumin.

In 2011, Dr. Helen Ratajczak, the President of Edmond Enterprises LLC and Professional of the Year for 2018 in Healthcare Therapy, looked into some concerns over injecting human DNA into another human and how that relates to autism. In the paper, she highlights that the thimerosal-free MMR II vaccine entered the market in 1979, but it wasn’t until 1983 it became the only available vaccine.

DR. Helen Ratajczak comments:

“Autism in the United States spiked dramatically between 1983 and 1990 from 4–5/10,000 to 1/500. In 1988, two doses of MMR II were recommended to immunize those individuals who did not respond to the first injection. A spike of incidence of autism accompanied the addition of the second dose of MMR II.”

She goes on to say how this MMR II vaccine was introduced in Britain in 1988.

She continues:

“[…] United Kingdom, which reported a dramatic increase in prevalence of autism to 1/64 […]. […]. It is important to note that unlike the former MMR, the rubella component of MMR II was propagated in a human cell line derived from embryonic lung tissue (Merck and Co., Inc., 2010).”


Sugar, sugar

It has been suggested the MMR II vaccine has the ability to trigger type 1 diabetes. Several studies have been published on this matter. One suggestion, which we found interesting, is not a peer-reviewed study, but a technical report on ResearchGate. On the author’s homepage his dedication to further research into the topic is evident.

The report notes that besides the measles, mumps and rubella live viruses, the major proteins in the vaccine come from the chicken embryo cell culture. It also notes a high correlation between the chicken culture proteins in the vaccine and type 1 diabetes.

How can this be?

Both animal and human cells carry a protein called glutamate decarboxylase (GAD). This is a protein associated with type 1 diabetes. The chicken proteins in the MMR II vaccine have been shown to create antibodies against GAD65 and GAD67 in chickens. Chicken and human GAD65 are 95% identical. The chicken GAD65 have then been shown to cross-react with human GAD65, which causes type 1 diabetes. (The numbers (65 and 67) depict the molecular mass of the protein). Because this report wasn’t a published research paper, we studied the references used in it and found they appeared to be from reliable sources.

As many of you may know, diabetes is directly related to beta cells produced in our pancreas.

One paper the author refers to in the above report concludes:

“The identification of β-cell proteins as autoantigens was perhaps the defining moment for type 1 diabetes as a disease, because it represented the first evidence that placed the disease in the pathogenetic category of autoimmunity.”

So, the vaccine may not contain aluminum or mercury, but it appears to have so many other ingredients it doesn’t need the help of either of these metals to trigger serious effects in infants or children.

If not mercury or aluminum…

Perhaps the most concerning known contaminant in the MMR II vaccine is glutamate, and MMR II seems to have a lot of it. Other ingredients include live viruses grown on culture that contains gelatin. As you may recall from a chapter in Part One of this book, gelatin is made from the bones and ligaments of farm animals.

In addition to its damaging effect on the shikimate pathway, glyphosate has other qualities that may potentially bring with it contaminants into the vaccine that are completely unforeseen and most likely their presence never tested for.

In 2017, scientists tested various vaccines for particles that were not intended ever to be in the vaccines. They tested three different MMR vaccines as detailed below.

Priorix manufactured by GlaxoSmithKline (GSK), of Italy. Among the particles found were tungsten, nickel and iron.

M-M-R vaxPro, manufactured by Sanofi Pasteur MSD, of France. Some of the particles found were stainless steel, platinum, silver, bismuth, iron and chromium.

Morupar, manufactured by what is known today as Novartis, in Italy, was the last MMR vaccine they tested. No particles were found in this vaccine.

An explanation for the presence of these metals could be the fact that glyphosate is very efficient at extracting metals. So, during the manufacturing stage if any of the equipment contain these types of particles, it’s highly likely the glyphosate may drag them along into the vaccine. It’s important to note here that the MMR II vaccine was not part of their study. We don’t know which particles, or if any, it contains.


Back to autism

Let’s return to the elephant in the room: the infamous autism tag associated with the measles portion of the MMR vaccine.

Can it be scientifically explained?

As we now know, the measles virus has the protein hemagglutinin on its surface. This is the part of the virus that’s used in the vaccine, which means our body will create antibodies against it.

As mentioned earlier, autoimmunity can result from foreign particles being so similar to our own, that the body thinks its own proteins are the enemy. This is the case with hemagglutinin, which looks a lot like our myelin basic protein (MBP). We need this protein in order to make myelin sheath. When we’re exposed to the measles protein (hemagglutinin), our body reacts the way the vaccine was designed: we make antibodies to it. A problem occurs when our body fails to see the difference between the hemagglutinin and our myelin basic protein, so in addition to attacking the invading virus, our antibodies now also start attacking our own proteins. This occurrence has been linked to autism.

In the study referenced above, the scientists studied abnormal antibodies in autistic children. In their study, they tested the blood in 125 autistic children and 92 control children (not autistic children) for antibodies. Out of the 125 children with autism, in 75 of them, or 60%, the researcher found a specific MMR antibody. This specific antibody, the authors explain, “is unique to the measles subunit of the vaccine.”

They then tested the blood that was MMR antibody positive for MBP autoantibodies. It turned out that 90% of the samples “were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism.”

Here, once again, we can see how molecular mimicry works on our immune system.

One of the authors of the above paper, neuroimmunologist Dr. Vijendra K. Singh, has studied this subject for quite some time. He suggests that autism could be triggered by a virus causing the body to attack its own myelin sheath.

In a 2009 paper, Dr. Singh explains:

“Many autistic children harbored brain myelin basic protein autoantibodies and elevated levels of antibodies to measles virus and measles-mumps-rubella (MMR) vaccine.”

The author explains that the autistic children also had elevated markers for systemic inflammation, which is the same as chronic inflammation.

When we looked closer into whether vaccines cause chronic inflammation, we uncovered numerous papers rejecting any such suggestion. Among those many papers was one from 2003 by Dr. Paul Offit regarding studies that claim:

“Consistent with critical differences between natural infection and immunization, well-controlled epidemiologic studies do not support the hypothesis that vaccines cause autoimmunity.”

An observational study was done in Yokohama, Japan. The authors used data from

Kohoku Ward spanning all cases of autism spectrum disorder (ASD) that fitted within ICD-10 guidelines for children up to seven years old, born in the period from 1988 to 1996.

The authors conclude:

“The significance of this finding is that MMR vaccination is most unlikely to be a main cause of ASD, that it cannot explain the rise over time in the incidence of ASD, and that withdrawal of MMR in countries where it is still being used cannot be expected to lead to a reduction in the incidence of ASD.”

What we found very interesting was the major rise in autism for those born in 1994. Even when considering the number of births each year, it doesn’t explain the skyrocketing rise in autism for those born that year.

We looked to see if the paper mentions any changes during 1994. The only change mentioned that could account for this, is a change in vaccine schedule. But then for those born in 1995 and 1996, the numbers dropped.

Considering the drop in total births in that two-year period, this could account for the fact that in November 1994, Yokohama’s city boundaries were changed and the city, on paper at least, became smaller. The authors didn’t believe this made a significant difference and continued the study using the new boundaries. They didn’t show what the result would have been had they continued using the original boundaries.


Vaccine friendly

Dr. Paul Thomas, author of the book The Vaccine Friendly Plan created his own vaccine schedule for his medical practice. In his revised vaccine schedule, he waits until the child is three years old before giving the MMR vaccine. In 2015, Dr. Thomas attended the public hearing in Oregon on Bill SB 442, which “seeks to remove all philosophical and religious exemptions to vaccines in the State of Oregon.”

The article says that during this hearing, Dr. Thomas states that:
“[…] he does not give every vaccine to every child in his practice, and as a result, he has over 1000 children in his practice over the age of 3, and NONE of them have autism. The rest of the country is seeing a rate of about one out of 50 children on the autism spectrum.”

Regardless of whether this means the MMR is linked to autism or not, if his statement is correct then we cannot help but think there must be some type of correlation between age, number of vaccines given and autism.

Dr. Thomas is not the only doctor who believes in staggering vaccines. Many healthcare professionals in the US are vaccinating their children on a schedule in which some vaccines are omitted while others are staggered. These schedules are not publicly acknowledged, but we must wonder what has caused these healthcare professionals to opt for a less aggressive vaccine schedule for their own children.

If the current official vaccine schedule is truly the best for our children, we wonder why the schedule differs from one country to another and why healthcare professionals sometimes choose their own vaccine schedule. How are we supposed to know which guidelines are best suited? Surely the concerns for childhood illnesses are similar regardless of which country you live in.

Excerpts (cont'd) from Chapter 40 of Vaccine Science Revisited: Are Childhood Immunizations As Safe As Claimed?:


Career suicide

It’s difficult to find researchers willing to put their names on papers showing any correlation between vaccines and adverse events.

There seems to be an overriding fear amongst medical professionals that suggesting vaccines trigger chronic disorders will lead to defamation or discreditation. This cautious approach, we feel, is very biased in itself, as it will discourage researchers from publishing their data or even doing the research to begin with.

(To avoid being discredited, or supposedly discredited, we have done our best to focus on authors and medical professionals with peer-reviewed or otherwise scientifically-accepted papers, studies and articles).

And here’s another bias, the so-called Healthy User Bias (HUB).

This bias covers issues such as when children prone to illnesses are not given the vaccines during safety trials. Therefore, these trials don’t represent the true population receiving the vaccines.

Just because health professionals and researchers have been defamed or publicly ridiculed, doesn’t mean they’re wrong. Most of them are highly educated, but take a more holistic and natural approach to medicine.

The views of these professionals seem to be in sync with the research we have shared with you in this book. Namely, that the antibodies our bodies create to fight foreign substances can become autoantibodies and attack the body’s own tissues, and also lead to chronic diseases. Diseases that are often worse than the infectious diseases they protect us from.

One of those illnesses can in some instances be a neurologic disease called subacute sclerosing panencephalitis (SSPE). This is a rare, chronic, progressive encephalitis that almost always ends in death. In fact, today, this disease is considered to be “a rare, slow viral infection caused by a defective measles virus.”

As with many other vaccine-related concerns, it’s difficult to find published papers on this matter. The best approach seems to be to source research unrelated to vaccines and study the ingredients in the vaccines. Not an ideal approach – and don’t we know it! It requires many hours extra reading.


References for Chapter 40: MMR – Autism and a ravaged immune system:

Cell Culture DISH. (2012, June13). FDA Issues Guidance for Warning Labels on All Drugs Produced Using Blood Products including Plasma-derived Albumin. Retrieved from https://cellculturedish.com/fda-issue...
Ratajczak, H.V. (2010). Theoretical aspects of autism: Causes—A review. Journal of Immunotoxicology, 8(1), 68-79
Ibid.
Ibid.
Arumugham, V. (2017). Role of MMR II vaccine contamination with GAD65 containing chick embryo cell culture in the etiology of type 1 diabetes. [Technical Report]. DOI: 10.5281/zenodo.1034770
ResearchGate. (n.d.). Vinu Arumugham. Retrieved form https://www.researchgate.net/profile/...
Roep, B. O., & Peakman, M. (2012). Antigen targets of type 1 diabetes autoimmunity. Cold Spring Harbor perspectives in medicine, 2(4), a007781.
Gatti, A.M. and Montanari, S. (2016). New Quality-Control Investigations on Vaccines: Micro- and Nanocontamination. Int J Vaccines Vaccin, 4(1): 00072.
Singh, V.K., Lin, S.X., Newell, E., and Nelson, C. (2002) Abnormal measles-mumps-rubella antibodies and CNS autoimmunity in children with autism. J Biomed Sci, 9(4), 359-364.
Ibid.
Ibid.
Wikipedia. (2018, October 6). Vijendra K. Singh. Retrieved from https://en.wikipedia.org/wiki/Vijendr...
Singh, V.K. (2009). Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism. Ann Clin Psychiatry, 21(3), 148-161.
Offit, P.A. and Hackett, C.J. (2003). Addressing Parents’ Concerns: Do Vaccines Cause Allergic or Autoimmune Diseases?. Pediatrics, 111(3), 653-659
Honda, H., Shimizu, Y., and Rutter, M. (2005) No effect of MMR withdrawal on the incidence of autism: a total population study. J Child Psychol Psychiatry, 46(6), 572-579.
Ibid.
Thomas, P. and Margulis, J. (2016). The Vaccine-Friendly Plan: Dr. Paul's Safe and Effective Approach to Immunity and Health-from Pregnancy Through Your Child's Teen Years. New York, N.Y: Ballantine books
Dr. Paul Approved. (n.d.). The Dr. Paul Approved Vaccine Plan. Retrieved from http://www.drpaulapproved.com/uploads...
Global Research. (2015, February 25). Vaccines Linked to Autism – Preserve Medical Freedom: Dr. Paul Thomas, M.D.. Retrieved from https://www.globalresearch.ca/vaccine...
Ibid.
Yilmaz, D., Aydin, O.F., Senbil, N., and Yuksel, D. (2006). Subacute sclerosing panencephalitis: Is there something different in the younger children? Brain and Development, 28(10), 649-652