Category: Child Development

For rodent pups, bonding with mom isn't hard-wired in the womb. It develops over the first few weeks of life, which is achieved by their maturing sense of smell, possibly allowing these mammals a survival advantage by learning to identify mother, siblings, and home.

Blended electrophysiological, biochemical, and behavioral experiments, Minghong Ma, PhD, an associate Professor of Neuroscience at the University of Pennsylvania School of Medicine, led a study published in a recent issue of the Journal of Neuroscience. With students Anderson Lee and Jiwei He, she demonstrated that neurons in the noses of mice mature after birth.

Using patch-clamping — a technique that measures electrical signals at the cellular level — Ma's team found that between birth and day 30 of development, normal neurons become six times more sensitive to their sibling's scent, in this case, a fragrance called lyral. In addition, the mice transition from a relative indiscriminate response to different odors to being highly attuned to one specific smell. They also respond to that specific odor with a faster speed over time.

The olfactory marker protein (OMP) likely mediates this developmental maturation. In olfactory sensory neurons lacking OMPs, response fails to speed up over 30 days as compared to normal neurons. The authors suggest this could be due to altered intracellular communication, since loss of the protein is associated with decreased phosphorylation of an associated enzyme called adenylate cyclase, a key player in the chemical signaling underlying the sense of smell.

The team also used a novel behavioral assay to illustrate one consequence of mistakes in this cellular maturation process. Normal mouse pups, given the choice between their mother and an unrelated, lactating female, will choose to huddle with or suckle their mother 78 percent of the time. But in the absence of OMP, newborn mice fail to make that distinction.

According to Ma, the maturation of olfaction in early development could offer animals that need nursing and care for a long time before maturing (altricial species, including some mammals) a survival advantage. Rather than being hard-wired at birth, Ma says, they learn to identify their surroundings and their family. "They actually learn to find their mother, home, and siblings, and to stay alive," she says. But whether the same is true of human infants, of course, remains an open question.

One key question yet to be addressed, Ma says, is the mechanism underlying this olfactory tuning process. How, for instance, do the cells develop a faster response speed? How do they get so good at focusing on just one odorant to the exclusion of all others? And can this process be modulated by early experience? The answers to those questions, she says, could possibly provide tools to influence the bonding between mother and child in early development, and even promote social interactions in autistic children.

The article was funded by the National Institute on Deafness and Other Communication Disorders, National Institutes of Health.

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Journal Reference:

1. A. C. Lee, J. He, M. Ma. Olfactory Marker Protein Is Critical for Functional Maturation of Olfactory Sensory Neurons and Development of Mother Preference. Journal of Neuroscience, 2011; 31 (8): 2974 DOI: 10.1523/JNEUROSCI.5067-10.2011

An Australian study to determine the likelihood of school-aged children waking up to their home smoke alarm found that 78% of children slept through a smoke alarm sounding for 30 seconds. The outcomes of the study are published March 7 in the journal Fire and Materials.

Home smoke detectors have been relied on since the 1960s, and have been known to save lives in domestic fires. The study's results show children are most at risk of not waking up to the sound of their home's smoke detector. Though related studies have been conducted in the past, the sample size used in this study has been the largest to date.

In order to gather data for the study, parents of 123 children (79 families) were asked to trigger their smoke alarm for 30 seconds after their child, or children, had been asleep for one to three hours. 60 boys and 63 girls were included in the study and the average age was 8.82 years. The group was split into two age groups so that the younger group would be prepubescent. This is because plasma melatonin levels drop with puberty onset and the melatonin hormone is known to be sleep-inducing. About 70% of the participants were aged from 5 — 10 years (87) and 30% from 11 — 15 years (36).

Volunteer parents reported whether or not their children woke using a research website, and the results showed that 78% of the children slept through the alarm. Of the small number of children who did wake up, only half recognized the sound as a smoke alarm, and half of those children knew they should evacuate. The data collected also showed that younger children (five to ten years old) were significantly more at risk, with 87% sleeping through the alarm, compared to 56% of 11-15 year olds.

"Parents should not rely on their children waking to the smoke alarm in the event of a fire and should not assume that they will immediately evacuate if they do wake up to a fire," says Dr. Dorothy Bruck, lead author of the study at Victoria University in Melbourne, Australia. "In summary, home safety plans should not assume children will wake up to an alarm. This data suggests fire safety training needs more emphasis on the need for children to evacuate the home in the event of an alarm sounding."

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Journal Reference:

1. D. Bruck, I. R. Thomas. Community-based research on the effectiveness of the home smoke alarm in waking up children. Fire and Materials, 2011; DOI: 10.1002/fam.1081

Just when children are faced with intensifying peer pressure to misbehave, regions of the brain are actually blossoming in a way that heighten the ability to resist risky behavior, report researchers at three West Coast institutions.

The findings — detailed in the March 10 issue of the journal Neuron — may give parents a sigh of relief regarding their kids as they enter adolescence and pay more attention to their friends. However, the research provides scientists with basic insight about the brain's wiring, rather than direct clinical relevance for now.

In the study, 24 girls and 14 boys from ethnically and socioeconomically diverse backgrounds underwent functional magnetic resonance imaging (fMRI) scans twice, at ages 10 and 13, the latter representing when children have moved into early adolescence. Each time, they were presented with photos of faces making neutral, angry, fearful, happy and sad emotional expressions.

Non-invasive fMRI, when focused on the brain, measures blood flow changes using a magnetic field and radio frequency pulses, producing detailed images that provide scientists with information about brain activity or help medical staff diagnose disease.

Researchers compared the fMRI results from age 10 to age 13, finding that activity increased significantly in the ventral striatum and the ventral medial portion of the prefrontal cortex over this three-year period. In addition to the scans, the researchers considered the children's self-reports on their ability to resist peer influences and engagement in risky or delinquent behavior.

The most enhanced response occurred in the ventral striatum, a brain region most frequently associated with reward-related processing. Over time, increases in brain activity there correlated with increases in children's resistance to peer influence.

"This is a complex point, because people tend to think of adolescence as the time when teenagers are really susceptible to peer pressure," said Jennifer H. Pfeifer, professor of psychology at the University of Oregon. "That is the case, but in addition to that added susceptibility they are also improving their ability to resist it. It's just that peer pressure is increasing because they spend a lot more time with peers during this time and less time with family. So it is a good thing that resistance to such influences is actually strengthening in their brains."

This study, which researchers believed to be the first to report longitudinal fMRI findings about changes in the way the brain processes emotion during this critical time of brain development, appears to fit into a growing body of evidence that ventral striatum development during early adolescence is critical to emotional regulation carried out by the brain's prefrontal circuitry, the researchers concluded.

"This is basic research that hopefully is laying the foundation for future studies with even more clinical relevance," said Pfeifer, director of the Developmental Social Neuroscience Lab. "We really have a lot to learn about how the brain responds to really basic emotional stimuli across development."

There was a surprise finding that deserves more study, though, Pfeifer said. Responses in the amygdala — a small almond-shaped mass centrally located deep in the brain — showed significant increases during this period only to the sad faces.

The amygdala plays a major role in emotional reactivity and indexing the salience of things in the environment. It's possible, Pfeifer said, that this response to sad faces could somehow be tied to the emergence of depression, especially in girls.

"This response in the amygdala raises questions we hope to pursue," she said. "The span from age 9 to 13 is critical in pubertal development. How do individual differences apply here? Identifying this response to 'sadness' in the amygdala opens the door to thinking about how changes in emotional reactivity might be related to the increase in depression that we see as kids enter puberty. Rates of depression are particularly enhanced for teen girls. Is this increased response to sad faces somehow part of that?"

Based on results of the new study, she added, "I think what we know about the ventral striatum may be poised to undergo a transformation over the next several years."

Six co-authors on the study with Pfeifer were: Carrie L. Masten of the Center for Mind and Brain at the University of California, Davis; William E. Moore III and Tasha M. Oswald, both doctoral students in the UO psychology department; John C. Mazziotta of the Ahmanson-Lovelace Brain Mapping Center at the University of California, Los Angeles; and Marco Iacoboni and Mirella Dapretto, both colleagues of Mazziotta and also with the FPR-UCLA Center for Culture, Brain, and Development at UCLA.

The National Center for Research Resources of the National Institutes of Health supported the research through three grants to the collaborating scientists.

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Journal Reference:

1. Jennifer H. Pfeifer, Carrie L. Masten, William E. Moore, Tasha M. Oswald, John C. Mazziotta, Marco Iacoboni, Mirella Dapretto. Entering Adolescence: Resistance to Peer Influence, Risky Behavior, and Neural Changes in Emotion Reactivity. Neuron, Volume 69, Issue 5, 1029-1036, 10 March 2011 DOI: 10.1016/j.neuron.2011.02.019

 A study published in the March 2011 Archives of Pediatrics and Adolescent Medicine shows that Massachusetts' new court-ordered mental health screening and intervention program led to more children being identified as behaviorally and emotionally at risk. The program is called the Children's Behavioral Health Initiative (CBHI).

The study, led by researchers from MassGeneral Hospital for Children (MGHfC), looked at Medicaid well-child visits that included behavioral screens from 2008-2009. They found that, under the new mandate, the number of screens completed in the state increased from 80,000 a year to 300,000 per year. The number of children with emotional/behavioral problems identified by the screens also more than tripled, from about 6,000 per year to more than 20,000 per year. A separate set of analyses showed that referrals for mental health evaluations for children with Medicaid also increased significantly in Massachusetts at this time.

The study's lead author, Karen Kuhlthau, PhD, of the MGHfC Center for Child and Adolescent Health Policy, says. "Increased screening is a first important step in assuring that children get the mental health services that they need."

Study co-author Michael Murphy, EdD, MGH Psychiatry, says, "Childhood psychosocial issues are among the most common and disabling conditions of children and adolescents, both in this country and in the rest of the world. Routine screening as a part of well-child care can enable pediatricians to recognize problems sooner and to provide help, preferably at an earlier point in time when intervention would be more effective and/or less costly."

This study primarily used the Pediatric Symptoms Checklist (PSC) as the mental health screening tool. Developed by the study's authors at Massachusetts General Hospital, the PSC is a 35-item questionnaire given to parents at their child's well-appointment visit. Parents check off NEVER, SOMETIMES, or OFTEN when asked questions pertaining to their child's' emotional and behavioral well being. Questions include whether a child "has school grades dropping," "gets hurt frequently" or "acts younger than children his or her age." The PSC can be easily scored to alert the pediatrician to a child's likely emotional difficulties.

The PSC has been used throughout the United States for more than two decades, and just this past week, it received national recognition when it won the endorsement of the National Quality Forum, a voluntary organization that advises the federal and state governments on the best ways to measure outcomes. With NQF endorsement, the PSC may be used to evaluate parts of the new US health care plan.

Additional co-authors of the Archives of Pediatrics and Adolescent Medicine report are Michael Jellinek, MD, chief of Psychiatry and Jeanne Van Cleave, MD, MassGeneral Hospital for Children; Gwyne White, Rutgers University; and Jack Simmons, PhD, Massachusetts Department of Health and Human Services. The costs of the study were paid for by a grant from The Fuss Family.

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Journal Reference:

1. Karen Kuhlthau; Michael Jellinek; Gwyne White; Jeanne VanCleave; Jack Simons; Michael Murphy. Increases in Behavioral Health Screening in Pediatric Care for Massachusetts Medicaid Patients. Arch Pediatr Adolesc Med, Mar 2011 DOI: 10.1001/archpediatrics.2011.18

 Most young adults who grow up with chronic illness graduate high school and have employment, but those with cancer, diabetes, or epilepsy are significantly less likely than their healthy peers to achieve important educational and vocational milestones, according to a report in the March issue of Archives of Pediatrics and Adolescent Medicine.

"In the United States, despite the variation in estimates, it is generally accepted that as many as 12 percent of children have special health care needs, including physical and emotional problems," the authors write as background information in the article. "With improved medical care during the past 40 years, most children with chronic illnesses survive into adulthood."

Gary R. Maslow, M.D., of the University of North Carolina at Chapel Hill, and colleagues analyzed data from the National Longitudinal Study of Adolescent Health to examine young adult outcomes in a nationally representative group of young men and women in the U.S. growing up with a chronic illness. The sample included 13,236 young adults aged 18 to 28. Those with asthma or non-asthmatic chronic illness — cancer, diabetes mellitus, or epilepsy — were compared with individuals who did not have these conditions.

Sixteen percent of the young adults in the sample had asthma, and 3 percent had cancer, diabetes, or epilepsy.

"Most young adults with chronic illness graduated high school (81.3 percent) and currently had employment (60.4 percent)," the authors report. "However, compared with healthy young adults, those with non-asthmatic chronic illness were significantly less likely to graduate high school, ever have had employment, or currently have employment and were more likely to receive public assistance."

Young adults with non-asthmatic chronic illness also had significantly worse young adult outcomes on all measures than those with asthma. "The non-asthmatic chronic illness group was less likely to have graduated high school, to ever have had employment, and to currently have employment and more likely to receive support from SNAP [the Supplemental Nutrition Assistance Program], to receive SSI/disability insurance, and to live with a parent/guardian," the authors write.

The authors believe continued efforts are needed to support children growing up with chronic illness to become successful adults — especially interventions that target educational attainment and vocational readiness.

"Pediatricians can play a role in promoting successful young adult outcomes by recognizing that such patients are at increased risk for educational, vocational, and financial problems," they conclude.

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Journal Reference:

1. G. R. Maslow, A. A. Haydon, C. A. Ford, C. T. Halpern. Young Adult Outcomes of Children Growing Up With Chronic Illness: An Analysis of the National Longitudinal Study of Adolescent Health. Archives of Pediatrics and Adolescent Medicine, 2011; 165 (3): 256 DOI: 10.1001/archpediatrics.2010.287

The satisfaction of young parents decreases with their number of children, while older parents are happier than their childless peers are. The more children young parents have, the unhappier they are. From age 40 on, however, it is the other way round. Then, more children generally mean more happiness. This is true independent of sex, income, or partnership status, as researchers of the Max Planck Institute for Demographic Research (MPIDR) in Rostock and the University of Pennsylvania now show in a study based on a survey of over 200,000 women and men in 86 countries conducted from 1981 to 2005.

"Children may be a long-term investment in happiness," says MPIDR demographer Mikko Myrskylä. Together with Rachel Margolis from the University of Pennsylvania in Philadelphia, USA, he published the new study in the latest issue of the journal "Population and Development Review." It shows a global trend: while for parents under 30 the level of happiness decreases with the first and each additional child, mothers and fathers aged 30 to 39 feel as happy as childless peers until they have four children or more. From age 40 onwards parents are even more content than childless couples are unless they have more then three children. Mothers and fathers over 50 are generally happier than their childless peers, no matter how numerous their offspring.

With a sound data basis, this study clarifies for the first time the discrepancy between the widespread belief that children bring happiness and the fact that most research finds either a negative or no significant relationship between parenthood and well being. "Seeing the age trend of happiness independent of sex, income, partnership status and even fertility rates shows that one has to explain it from the perspective of the stage of parents life," says Mikko Myrskylä who at the MPIDR is heading the Max Planck Research Group "Lifecourse Dynamics and Demographic Change."

In the early stages of parenting, positive aspects of having children are overshadowed by negative experiences such as lack of sleep, concerns about the child's well being, and financial strains. The older parents get, the less they feel such pressure caused by their offspring as the child grows up and becomes more independent. When children reach adulthood their parents, who are then between 40 and 60 years old, can benefit from them financially and emotionally. Consistently, the study finds that the satisfaction of parents over 40 rises with the number of children comparatively strongly in former socialist states. Welfare systems in these countries are less far developed and parents depend more on direct financial support from their children.

Governments also play a role in enhancing the happiness of young parents. In former socialist countries like Russia, Poland and Hungary that offer limited support for parents of young children, their contentment compared to childless peers decreases particularly strongly with the number of children. In contrast, the curve is rather flat in countries with more developed welfare states like Western Germany, Austria and Switzerland. In these countries peers with and without children feel similarly well at any age. At the same time the influence of children as a source of happiness seems to be rising over time. From 1997 to 2005 parents of all ages reported feeling happier than they did in the period from 1981 to 1996.

The results of this study are based on data from more than 200,000 women and men over fifteen years old questioned for the World Value Surveys (WVS) from 1981 to 2005. The WVS is the largest international survey including questions concerning happiness and fertility.

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Journal Reference:

1. Rachel Margolis, Mikko Myrskyl. A Global Perspective on Happiness and Fertility. Population and Development Review,.

 Rapidly improving technology is changing everyday life for all generations. This constantly changing environment can be a difficult adjustment for older generations. However, for the current generation known as "Generation Y," this sense of constant technology adaption isn't an adjustment; it is a way of life. A University of Missouri researcher says a widening gap is occurring between educators and students due to the difference in how older and younger generations approach evolving technologies. Newton D'Souza, an assistant professor of architectural studies at MU, is looking for ways to move beyond traditional teaching methods and to bridge the technology gap between teachers and students.

"In a traditional educational model, learning only occurs in the classroom," MU researcher Newton D'Souza said. "Now, with technology like laptops and mobile phones, learning can occur anywhere from classrooms to hallways to coffee shops. For older generations, technology is a separate fixture. For Generation Y, it's a part of their lives. On one hand, it is exciting; on the other hand, it challenging because we must find ways to adjust teaching styles."

Researchers at the University of Missouri are studying ways to integrate technology into design learning, specifically to learn how to teach children design basics. In an effort to study how children who have grown up in a wired, video game culture use technology, D'Souza engaged young students using a 3D virtual reality platform to teach design. Using a popular existing virtual reality platform called Second Life, researchers directed students to design a small zoo. The zoo project involved a topic that young students could relate to, while providing adequate research restraints.

The Second Life platform provided a realistic 3D spatial simulation for students to explore. They were given instructions on certain design specifics and then allowed to work within the simulation. By studying how the students worked within the virtual reality platform and their eventual design product, D'Souza was able to observe the improvement of specific design skills.

D'Souza found that students working within the 3D virtual reality environment tended to improve spatial skills, including kinesthetic and logical abilities. However, verbal and intrapersonal skills seemed to suffer. He attributed this mixed result as a lesson to constantly work on creating better interfaces for today's learners. D'Souza also was surprised to find how quickly the students grasped the virtual reality concept and were able to begin working with it.

"Because they are wired in media, the kids entered into the system much faster than we expected," D'Souza said. "Today's students already exist in a 3D environment; we need to find a way to teach them where they already are."

Ultimately, D'Souza says that because each individual learns differently, new media technologies like the Second Life platform will teach researchers even more about how students learn. He believes it is important to continually question the assumptions about how humans learn.

"Right now we are failing to communicate with younger children," D'Souza said. "Learning is effective when previous assumptions are questioned, and nothing is taken for granted. It's not that we should entirely abandon our traditional teaching techniques; we need to consolidate what we have, and yet improvise to meet the needs of current day learners."

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Journal Reference:

1. Newton D’Souza, So-Yeon Yoon, Zahidul Islam. Understanding design skills of the Generation Y: An exploration through the VR-KiDS project. Design Studies, 2011; 32 (2): 180 DOI: 10.1016/j.destud.2010.07.002

 Blood group incompatibility between Henry VIII and his wives could have driven the Tudor king's reproductive woes, and a genetic condition related to his suspected blood group could also explain Henry's dramatic mid-life transformation into a physically and mentally-impaired tyrant who executed two of his wives.

Research conducted by bioarchaeologist Catrina Banks Whitley while she was a graduate student at SMU (Southern Methodist University) and anthropologist Kyra Kramer shows that the numerous miscarriages suffered by Henry's wives could be explained if the king's blood carried the Kell antigen. A Kell negative woman who has multiple pregnancies with a Kell positive man can produce a healthy, Kell positive child in a first pregnancy; But the antibodies she produces during that first pregnancy will cross the placenta and attack a Kell positive fetus in subsequent pregnancies.

As published in The Historical Journal (Cambridge University Press), the pattern of Kell blood group incompatibility is consistent with the pregnancies of Henry's first two wives, Katherine of Aragon and Anne Boleyn. If Henry also suffered from McLeod syndrome, a genetic disorder specific to the Kell blood group, it would finally provide an explanation for his shift in both physical form and personality from a strong, athletic, generous individual in his first 40 years to the monstrous paranoiac he would become, virtually immobilized by massive weight gain and leg ailments.

"It is our assertion that we have identified the causal medical condition underlying Henry's reproductive problems and psychological deterioration," write Whitley and Kramer.

Henry married six women, two of whom he famously executed, and broke England's ties with the Catholic Church — all in pursuit of a marital union that would produce a male heir. Historians have long debated theories of illness and injury that might explain the physical deterioration and frightening, tyrannical behavior that he began to display after his 40th birthday. Less attention has been given to the unsuccessful pregnancies of his wives in an age of primitive medical care and poor nutrition and hygiene, and authors Whitley and Kramer argue against the persistent theory that syphilis may have been a factor.

A Kell positive father frequently is the cause behind the inability of his partner to bear a healthy infant after the first Kell negative pregnancy, which the authors note is precisely the circumstance experienced with women who had multiple pregnancies by Henry. The majority of individuals within the Kell blood group are Kell negative, so it is the rare Kell positive father that creates reproductive problems.

Further supporting the Kell theory, descriptions of Henry in mid-to-late life indicate he suffered many of the physical and cognitive symptoms associated with McLeod syndrome — a medical condition that can occur in members of the Kell positive blood group.

By middle age, the King suffered from chronic leg ulcers, fueling longstanding historical speculation that he suffered from type II diabetes. The ulcers also could have been caused by osteomyelitis, a chronic bone infection that would have made walking extremely painful. In the last years of his life, Henry's mobility had deteriorated to the point that he was carried about in a chair with poles. That immobility is consistent with a known McLeod syndrome case in which a patient began to notice weakness in his right leg when he was 37, and atrophy in both his legs by age 47, the report notes.

Whitley and Kramer argue that the Tudor king could have been suffering from medical conditions such as these in combination with McLeod syndrome, aggravated by his obesity. Records do not indicate whether Henry displayed other physical signs of McLeod syndrome, such as sustained muscle contractions (tics, cramps or spasms) or an abnormal increase in muscle activity such as twitching or hyperactivity. But the dramatic changes in his personality provide stronger evidence that Henry had McLeod syndrome, the authors point out: His mental and emotional instability increased in the dozen years before death to an extent that some have labeled his behavior psychotic.

McLeod syndrome resembles Huntington's disease, which affects muscle coordination and causes cognitive disorder. McLeod symptoms usually begin to develop when an individual is between 30 and 40 years old, often resulting in damage to the heart muscle, muscular disease, psychiatric abnormality and motor nerve damage. Henry VIII experienced most, if not all, of these symptoms, the authors found.

Fetal Mortality, Not Infertility Is the Kell Legacy

Henry was nearly 18 when he married 23-year-old Catherine of Aragon. Their first daughter, a girl, was stillborn. Their second child, a boy, lived only 52 days. Four other confirmed pregnancies followed during the marriage but three of the offspring were either stillborn or died shortly after birth. Their only surviving child was Mary, who would eventually be crowned the fourth Monarch in the Tudor dynasty.

The precise number of miscarriages endured by Henry's reproductive partners is difficult to determine, especially when various mistresses are factored in, but the king's partners had a total of at least 11 and possibly 13 or more pregnancies. Only four of the eleven known pregnancies survived infancy. Whitley and Kramer call the high rate of spontaneous late-term abortion, stillbirth, or rapid neonatal death suffered by Henry's first two queens "an atypical reproductive pattern" because, even in an age of high child mortality, most women carried their pregnancies to term, and their infants usually lived long enough to be christened.

The authors explain that if a Kell positive father impregnates a Kell negative mother, each pregnancy has a 50-50 chance of being Kell positive. The first pregnancy typically carries to term and produces a healthy infant, even if the infant is Kell positive and the mother is Kell negative. But the mother's subsequent Kell positive pregnancies are at risk because the mother's antibodies will attack the Kell positive fetus as a foreign body. Any baby that is Kell negative will not be attacked by the mother's antibodies and will carry to term if otherwise healthy.

"Although the fact that Henry and Katherine of Aragon's firstborn did not survive is somewhat atypical, it is possible that some cases of Kell sensitization affect even the first pregnancy," the report notes. The survival of Mary, the fifth pregnancy for Katherine of Aragon, fits the Kell scenario if Mary inherited the recessive Kell gene from Henry, resulting in a healthy infant. Anne Boleyn's pregnancies were a textbook example of Kell alloimmunization with a healthy first child and subsequent late-term miscarriages. Jane Seymour had only one child before her death, but that healthy firstborn also is consistent with a Kell positive father.

Several of Henry's male maternal relatives followed the Kell positive reproductive pattern.

"We have traced the possible transmission of the Kell positive gene from Jacquetta of Luxembourg, the king's maternal great-grandmother," the report explains. "The pattern of reproductive failure among Jacquetta's male descendants, while the females were generally reproductively successful, suggests the genetic presence of the Kell phenotype within the family."

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Journal Reference:

1. Catrina Banks Whitley, Kyra Kramer. A New Explanation for the Reproductive Woes and Midlife Decline of Henry VIII. The Historical Journal, 2010; 53 (04): 827 DOI: 10.1017/S0018246X10000452

Cerebral palsy is a neurodevelopmental condition that affects motor function, more often in children born prematurely. Because cerebral palsy is a result of brain injury received shortly before, during, or soon after birth, the number of infants being diagnosed with the condition is a good indicator of the quality of perinatal and neonatal care. An article soon to be published in the Journal of Pediatrics indicates that the rates of cerebral palsy have declined dramatically in the past 15 years.

Dr. Ingrid van Haastert and colleagues from the University Medical Center Utrecht in The Netherlands studied nearly 3000 infants born prematurely between 1990 and 2005. They found that 2.2% of the infants born between 2002 and 2005 were diagnosed with cerebral palsy, down from 6.5% for those born between 1990 and 1993. Such a dramatic decrease in the rate of cerebral palsy diagnoses provides evidence that care for infants right before, during, and shortly after birth has improved in the last 15 years.

The researchers also found that children who were diagnosed with cerebral palsy between 2002 and 2005 were less severely affected by the condition than those diagnosed earlier in the study. Among the infants studied, the most important risk factors for developing severe cerebral palsy were large hemorrhages and/or white matter lesions in the brain. "We found that a decrease in the occurrence of extensive cystic white matter lesions was the main reason for the fall in severe cerebral palsy," Dr. van Haastert explains.

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Journal Reference:

1. Ingrid C van Haastert et al. Decreasing Incidence and Severity of Cerebral Palsy in Prematurely Born Children. Journal of Pediatrics, (in press) DOI: 10.1016/j.jpeds.2010.12.053

— A pediatric brain tumor that causes gruesome suffering is finally yielding its secrets. For the first time, scientists at the Stanford University School of Medicine have cultured human cells from this cancer, Diffuse Intrinsic Pontine Glioma, and used those cells to create an animal model of the disease. Their discoveries will facilitate research on new treatments for DIPG, a tumor of school-aged children that is now almost universally fatal.

The advances come thanks to the parents of young cancer victims, who donated their deceased children's brain tumors for research in the hopes of sparing other families the pain they had experienced. Because of its location in the brain stem, this cancer is rarely biopsied, so scientists have had few previous opportunities to examine the tumors.

A diagnosis of DIPG is "a death sentence for kids," said John Jewett, whose son Dylan died of DIPG in 2009 at age 5. "No parent should have to hear that, but doctors can't study the disease unless somebody makes a donation." John and his wife, Danah, were the first parents to donate their child's tumor to the Stanford team.

"These donations open up the world in terms of being able to study this tumor, understand the biology behind its growth and develop therapies," said Michelle Monje, MD, PhD, an instructor in neurology and neurological sciences at Stanford who is the primary author of the new study, which will be published online Feb. 28 in Proceedings of the National Academy of Sciences.

The Stanford team's findings include new insight into molecular signals that prompt the cancer to grow. The signals could be good targets for anti-tumor drugs.

"So little is known about this disease," said Philip Beachy, PhD, professor of developmental biology and senior author of the study. "This work has the potential of moving us a huge step forward, particularly with the identification of a specific pathway important in the biology of the tumor, which could serve as a therapeutic target."

Treatment advances for DIPG have been stagnant for 35 years, said Monje, who treats DIPG patients at Lucile Packard Children's Hospital, where she was Dylan Jewett's doctor. The cancer primarily affects children ages 5 to 9, striking 200 to 400 children per year in the United States and killing quickly. Radiation therapy offers temporary remission, but patients soon relapse; just one victim in 100 survives five years. No effective chemotherapy drugs exist, and, because the malignant cells entwine themselves with healthy cells in a region of the brain stem essential for life, surgery is impossible. The disease takes away control of basic body functions such as talking, swallowing and moving one's eyes or limbs, but leaves victims aware of what is happening as their condition declines.

"It's horrific," Monje said.

The researchers began their investigation by focusing on a specific molecular signaling pathway, known as the Hedgehog pathway, that they thought might be driving development of DIPG cells. The Hedgehog pathway has already been shown to play a role in the growth of several other kinds of brain tumor. The team's early experiments supported the idea that the Hedgehog pathway is part of the pathology of DIPG, suggesting that it would be a good target for drugs.

As part of their work, the scientists isolated DIPG tumor cells from brain tissue of two young DIPG victims and grew the cells in the lab. Other institutions have attempted to grow similar primary tissue cultures, but the Stanford team is the first to succeed, thanks in large part to the expertise of Siddhartha "Sid" Mitra, PhD, a postdoctoral research scholar in neurosurgery.

The researchers' experiments also included introducing human DIPG cells to the brains of healthy mice, which revealed that the cancer cells would form DIPG-like tumors. They plan to use this xenograft model to perform further studies of DIPG biology and to conduct early stage tests of potential drugs.

"Just having this model makes possible a real attack on the problem," Beachy said.

Several pharmaceutical companies are currently developing drugs to inhibit the Hedgehog signaling pathway, and two drugs already approved by the FDA for other purposes have been found to have anti-Hedgehog activity. Such drugs will form the basis for the Stanford team's upcoming research on DIPG therapies in the mouse model and in children with the disease.

For the families who donated their children's tumors to the Stanford research, the gift provides an opportunity to have some good come from a terrible personal tragedy. For Dylan Jewett's parents, grieving the loss of a little boy who had loved pretending to be a superhero, hugging his baby brother and building tracks for his Thomas the Tank Engine train, the donation seemed like the only thing to do.

"We couldn't think not to," said Danah Jewett of her family's decision to give Dylan's tumor for research. "Our options were to try and help, or to let him die in vain. Now we feel like his story lives on."

In addition to Monje, Beachy and Mitra, the Stanford team included research assistants Morgan Freret and Marilyn Masek; postdoctoral scholars Joanne Attema, PhD, Tal Bachar Raveh, PhD, and James Kim, MD; neurosurgery resident Gordon Li, MD; Michael Edwards, MD, professor of pediatrics and of neurosurgery; Paul Fisher, MD, professor of pediatrics, of neurosurgery and of neurology & neurological sciences; Irving Weissman, MD, professor of pathology and of developmental biology; Terri Haddix, MD, clinical assistant professor of pathology; Hannes Vogel, MD, professor of pathology and of neurosurgery; and Albert Wong, MD, professor of neurosurgery. Beachy, Edwards, Fisher, Weissman and Vogel are also members of the Stanford Cancer Center, and Beachy and Weissman are members of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

Beachy holds stock in and receives royalties from patents licensed to Curis, a biotechnology firm now developing drugs with anti-Hedgehog signaling activity.

The research was funded by the Kyle O'Connell Foundation, the Dylan Jewett Family Fund, the Sence Foundation, the Childhood Brain Tumor Foundation, the Pediatric Brain Tumor Foundation, the National Institutes of Health, the National Brain Tumor Foundation and the Howard Hughes Medical Institute.

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Journal Reference:

1. M. Monje, S. S. Mitra, M. E. Freret, T. B. Raveh, J. Kim, M. Masek, J. L. Attema, G. Li, T. Haddix, M. S. B. Edwards, P. G. Fisher, I. L. Weissman, D. H. Rowitch, H. Vogel, A. J. Wong, P. A. Beachy. Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1101657108