Patient Presentation
A 36-hour-old, 38 6/7 week male in the newborn nursery was noted to be more yellow in his skin color. He was acting well, and attempting to breastfeed. He had had 2 wet diapers and 1 stool since birth. He was a first baby for the parents and the mother was A+ and baby was 0+. Coombs testing was pending. The total cutaneous bilirubin was 10.2 mg/dL which was above the instrument’s threshold for accuracy and also the recommendations for serum testing. A repeated serum total bilirubin was 12.8 mg/dL which was above the threshold of 12.4 mg/dL for starting phototherapy.

The pertinent physical exam showed a healthy male who was jaundiced. Birth weight was 3473 grams and currently was 3299 grams at 24 hours (down 5%). His exam was otherwise normal.

The diagnosis of hyperbilirubinemia was made. The new intern said that she had not ordered phototherapy before and wasn’t sure how many lights to order. “That’s a good question. I don’t work in the newborn nursery a lot, but the notes I see from lots of babies who I see after discharge usually have 3 or 4 lights ordered along with a biliblanket to be put underneath them. We have to order the nurses to use an isolette so hypothermia doesn’t become an issue. The nurses still monitor the temperature closely though in the isolette. Why don’t we check with the nursing staff who do this a lot, and then if we still aren’t sure then we can call on the neonatologists. I know that we do intense treatment which usually means less time the baby needs to be treated,” he replied. The patient’s clinical course showed that the nursing staff recommended to use 3 lights along with the biliblanket, and after 12 hours of therapy, the bilirubin level was down and remained down 6 hours after the phototherapy was discontinued. He was discharged with followup in 1 day in the outpatient setting.

Discussion
Bilirubin is a metabolite of heme degradation. Heme is oxidized to biliverdin which is then reduced to bilirubin. Bilirubin is then taken up into the liver and conjugated; conjugated bilirubin is then excreted through the gastrointestinal tract. Bilirubin can also be converted by a blue light at wavelength 450 nm into a water-soluble compound called lumirubin which is then excreted through the kidneys.

The differential diagnosis of neonatal unconjugated hyperbilirubinemia can be reviewed here.

Learning Point
Phototherapy treatment for hyperbilirubinemia has been used as standard of care for hyperbilirubinemia of infancy for many years with many studies have attempted to quantify the optimal treatment. The American Academy of Pediatrics 2022 Clinical Guidelines states that: “[t]he effectiveness of phototherapy is dependent on the intensity of phototherapy administered and the surface area of the infant exposed to phototherapy (ie, double-sided). Unfortunately, no standard method for delivering phototherapy exists and there is substantial variation in phototherapy equipment.”

They further state, “[c]omprehensive information about phototherapy, including its mechanism of action and strategies for its use, can be found in the Appendix to the 2004 guideline, a technical report of the AAP Committee on Fetus and Newborn, and comprehensive recent reviews. The general approach is to provide intensive phototherapy to as much of the infant’s surface area as possible. Intensive phototherapy requires a narrow-spectrum LED blue light with an irradiance of at least 30 mW/cm² per nm at a wavelength around 475 nm. Light outside the 460 to 490 nm range provides unnecessary heat and potentially harmful wavelengths. The advantage of intensive phototherapy is that it can quickly lower the [total serum bilirubin] and should shorten the duration of treatment.”

A British Medical Journal Clinical Evidence Review also stated that, “It is generally accepted that intensive phototherapy applied to infants with already high serum bilirubin levels or rapidly rising serum bilirubin levels has greatly reduced the need to exchange transfusion in infants with or without haemolysis.”

Sunlight could be used as a potential treatment. However it caries risk of dehydration, sunburn, and hypothermia. Even with sunlight filters hypothermia continues to be a major issues.

A Cochrane Collaboration review found that “Sunlight may be an effective adjunct to convention phototherapy in [low or middle income countries] settings, may allow for rotational use of limited phototherapy machines and may be preferable to families as it can allow for increased bonding. Filtration of sunlight to block harmful ultraviolet light and frequent temperature checks for babies under sunlight may be warranted for safety. Sunlight may be effective in preventing hyperbilirubinemia in some cases, but these studies have not demonstrated that sunlight alone is effective for the treatment of hyperbilirubinemia given its sporadic availability and the lower or very low certainly of the evidence in these studies.”

The American Academy of Pediatrics reiterates this information stating: “[a]lthough direct exposure to sunlight has been shown to decrease [total serum bilirubin] concentrations, the practical difficulties involved in safely exposing infants to the sun, either inside or outside, while also avoiding sunburn preclude the use of sunlight as a reliable therapeutic tool, and therefore, it is not recommended. Although filtered sunlight has been safely used in resource-constrained settings where phototherapy is not readily available, these guidelines were not developed for use in such settings.””

Questions for Further Discussion
1. What causes direct hyperbilirubinemia? A review can be found here
2. What screening testing is recommended routinely for newborn infants?
3. What causes hyperbilirubinemia in an older infant or child?

Related Cases

Disease: Jaundice

Symptom/Presentation: Jaundice

Specialty: General Pediatrics | Neonatology

Age:Newborn

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Jaundice

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Woodgate P, Jardine LA. Neonatal jaundice: phototherapy. BMJ Clin Evid. 2015;2015:0319.

Horn D, Ehret D, Gautham KS, Soll R. Sunlight for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates. Cochrane Database Syst Rev. 2021;2021(7):CD013277. doi:10.1002/14651858.CD013277.pub2

Kemper AR, Newman TB, Slaughter JL, et al. Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. 2022;150(3).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Patient Presentation
A 20-year-old male was going on a 10 day trip to Europe as part of a study abroad experience. His main concern was jet lag and how he could mitigate its problems. His pediatrician and he discussed his normal sleep pattern which was erratic with onset and duration. Most nights he would go to sleep between 1-3 AM and sleep only for 6 hours. He said that this was because of school work and social activities which were in person or online. He denied having any problems initiating sleep once he decided it was time to go to sleep.

The pertinent physical exam showed normal vital signs and his weight and length were 50% and 25% respectively. His examination was normal.

The diagnosis of a healthy male with social jet lag with was made. The pediatrician discussed appropriate sleep hygiene including having a more consistent and normal sleep time. She noted that it is hard in a college dorm situation to not use the bed for studying and social activities but recommended he try to do this. She also recommended that he move the phone out of his reach when sleeping and potentially even use a regular alarm clock that he could quickly turn off to wake himself up instead of using his phone alarm. For the trip to Europe she recommended that he actually move his bedtime back into the evening hours and wake up a bit earlier in the morning for a few days before the trip to shift his sleeping. “I recommend that you eat a real meal in the airport and then once you get on the plane put on some eye shades, ear plugs and use a neck pillow right away to try to get to sleep. That way you have eaten and don’t have to wait for the food service onboard, plus you hopefully will be somewhat tired and can get some sleep on the plane. You should also have a water bottle with you because you likely will need to drink and that way you don’t have to get up and ask for water. I also recommend that once you are awake for the first day, that you do something active to stay awake, so you are very tired the first night in Europe and you can sleep well, ” she recommended. “Okay – eat in the airport, go to sleep right away and once I’m up, I’m up for the day. That should be easier as we are supposed to take a city tour when we land,” he repeated. “I’ll try the other stuff too, but it’s hard to not be online when my friends are there too,” he said. “One thing maybe you all could do, is to turn the phones off together for most nights. That way everyone can get some sleep,” she suggested. He looked skeptical but nodded in agreement.

Discussion
Jet lag is a chronic sleep deprivation that is associated usually with travel across time zones. This is due to the usual timing of the circadian rhythms being upset due to external expectations of normal activities in the new locations. The greater the time zone change and overall deprivation, often the more difficult it is to make the change. Some use a general rule that it takes 1 day for each 1 hour of time zone change to make up for the jet lag. Some people are more sensitive with the direction of the change. Traveling eastward is often associated with the potential opportunity to get some sleep going to sleep earlier but needing to awaken earlier with a shortened total sleep time. Traveling westward often extends the daytime hours during travel because of the need to awaken early to leave on the trip. It does have the opportunity potentially to nap, but there is still a need to stay awake longer until nighttime in the westward destination arrives. Too much napping can also make it more difficult to make the change.

Social jet lag is a delayed sleep phase disorder that “results from a mismatch between social, educational, and biological sleep-wake timing.” These are patients who can’t sleep because they have learned to have a “high alertness levels at sleep time and sleepiness during daylight house, particularly the mornings.” This results in chronic sleep deprivation and many studies support decreased classroom learning and effectiviness. These patients develop long sleep latencies for the bedtime that is appropriate for them, thus shifting their sleeping time to later, and with this shift having a more normal sleep latency with the later bedtime. For example, it takes 1 hour to fall asleep at midnight but only 10 minutes at 2 AM. Patients again have chronic sleep deprivation because they need to get up in the morning for school, work, etc.

Some patients will also have a conditioned insomnia. Beds used to be for sleeping, but for many teens and young adults they are also used for work, and social activities. Thus the bed is not a relaxing place to rest and sleep, but is a place to remain brain active and thus awake.

Chronic sleep deprivation is highly likely if the patient has “frequent, big, weekend sleep-ins” of more than 2 hours from usual awakening time, and/or has a “great trouble waking up, getting out of bed and getting moving on school mornings.” There is a limited amount of time to do any daily activities in the morning with causes the functional problem of being late or missing school. It can be hard to know if a teen has chronic sleep deprivation or is just moody or poorly engaged and grumpy. If these are excessive or causing functional problems, likely chronic sleep deprivation is at least part of the problem.

Learning Point
Recommendations for travel jet lag in additional to 1 day of adjustment per time zone change include:

• Limiting caffeine while traveling
• Eating healthy meals on the new destination schedule as much as possible for a few days before or day of travel
• Use layered clothing to keep oneself at a comfortable body temperature
• Cutting out the light and noise by using eye shades and ear plugs/headphones. Light is a stimulator of increased wakefulness.
• Planning morning arrivals if possible (see eastward travel above)
• Use of melatonin may or may not help some people

Recommendations for help with social jet lag include:

Creating a light’s out time. This needs to be negotiated with the teen/young adult but should allow for 9 hours of sleep for lower high school aged person or younger, and 8 hours for upper high school or older person.

The bed should be only used for sleeping not other activities even during the daylight hours. No homework, eating, socializing, etc. in the bed. Lights off and in bed should be good external factors to help with consistent sleep.

Phone, computer, and TV (anything with a screen) should not be in the bedroom if at all possible. This goes for all members of the house to help with enforcement. This may take time to establish and enforce.

Sleep in on the weekend. This can be helpful if not too long ( 120 minutes) this can actually make the sleep problem worse by reinforcing the late sleep initiation.

Bedtime routine that is quieter and consistent as much as possible also is helpful.

Sleep constriction (bedtime later than average) can be helpful by causing the patient to be more tired and thus move their own sleep initiation time backward to a normal time (sleep fading). This is done for up to 6 weeks and seems to work for patients with delayed circadian rhythms. It is not helpful for those that voluntarily are decreasing their sleep.

Questions for Further Discussion
1. What are health problems associated with chronic sleep deprivation?

2. What other sleeping tips do you recommend for social jet lag?

3. What travel tips are there for studying abroad? A review can be found here

Related Cases

Disease: Jet Lag and Social Jet Lag | Sleep Disorders | Traveler’s Health

Symptom/Presentation: Sleep Disturbance

Specialty: Adolescent Medicine | General Pediatrics | Travel Medicine

Age: Young Adult

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Traveler’s Health and Sleep Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Coel RA, Pujalte GGA, Applewhite AI, et al. Sleep and the Young Athlete. Sports Health. 2022;15(4):537-546. doi:10.1177/19417381221108732

Seton C, Fitzgerald DA. Chronic sleep deprivation in teenagers: Practical ways to help. Paediatric Respiratory Reviews. 2021;40:73-79. doi:10.1016/j.prrv.2021.05.001

Huang WY, Feng J, Zheng C, Jiao J, Wong SHS. Associations of social jetlag with physical activity and sedentary behaviour in children and adolescents: A systematic review and meta-analysis. Journal of Sleep Research. 2024;33(1):e13997. doi:10.1111/jsr.13997

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Patient Presentation
A 2-day-old female was in the newborn nursery. She was a term infant, born to a G2P2 mother without complications. It was noted before rounds that she was almost 48 hours old and had not passed any meconium. She was acting normally and breastfeeding well every 2-3 hours. Her routine labs had been sent at 24 hours of age including her newborn screening test and its results were pending.

The pertinent physical exam showed her birth weight of 3.489 kg which was down only 4%. Her head circumference and length were about 50%. She was mildly jaundiced with a transdermal bilirubin of 4.7 mg/dL. Her examination was normal. She had no sacral anomalies, her lower extremity reflexes were normal, and her anus appeared in a normal position with a tiny amount of meconium on the anal folds.

The diagnosis of a healthy female infant who had not yet passed meconium was made. The attending and resident discussed the potential differential diagnosis. While seeing the other babies during rounds, the nurse messaged the pediatricians that the infant had had a large meconium stool at 51 hours of life. The patient’s clinical course as of 1 month of age, showed that the infant had been passing regular stools without any problems and was growing well.

Discussion
Clinicians who work with newborn infants are similar to systems engineers. They need to make sure that all of the major organ systems are working as they should be at birth and making the appropriate transition to full operations over the first few days. Obviously the cardiorespiratory system needs to be working from the start, but other systems such as the urinary and gastrointestinal systems should start working soon after birth.

According to a 1977 study of 500 consecutive infants of all gestational ages, first void was within 24 hours for all infants. First stool was within 48 hours for 499 infants. Most first stools were within the first 24 hours (N=395, 98.5% for term infants, N= 80, 76.3% for preterm infants and N=25, 100% for post term infants) Delayed passage is usually considered after 48 hours.

Babies with delayed passage of meconium may be well appearing and have a normal physical examination. They can also present with obstructive symptoms include abdominal distention, poor feeding, vomiting, and respiratory problems.

Prematurity issues have increased because of the incredible medical advances in neonatology and obstetrics. More mothers are being treated with various medications, babies are often younger and have more respiratory problems and/or infections which can cause delayed meconium passage. More extremely premature infants simply have not developed their gastrointestinal neural connections to be able to have normal peristalsis and evacuation in the way an older premature infant or full term infant does. On the plus side in the US, more infants are being identified with possible cystic fibrosis prenatally or with newborn screening. Similarly hypothyroidism is usually identified early because of newborn screening.

An anteriorly positioned anus still allows stool passage but it is more difficult as the rectum/anus is longer and also the angle relative to the skin is more acute. Imperforate anus usually can be identified on physical examination. It should be noted that fistulas may still have passage of stool but potentially symptoms will be more constipation like or the stool is smaller/ribbon-like. Other abnormalities may cause bilious emesis which is a medical emergency. A review can be found here.

Hirschsprung disease (HD) is one of the most common dysmotility problems associated with delayed passage of meconium and often is the first cause clinicians consider. HD is caused by agangionic bowel that begins at the rectum/anus and ascends. It can affect the entire colon but often there is a transition point between normally innervated colon and non-innervated colon which can be identified on contrast enema. Anorectal manometry can help with the diagnosis but colonic biopsy is the definitive test.

Evaluation and treatment for delayed passage of meconium is not standardized. Assuming there is normal external anatomy and the infant is well, patency testing is commonly used as a first evaluation/treatment method. This can be insertion of a tube and/or medication such as a glycerin suppository. This not only tests patency within the first couple of centimeters of colon but may also stimulate evacuation. Contrast enema again provides not only evaluation for Hirschsprung disease, meconium ileus, and potential anatomic abnormalities, but often is therapeutic by stimulating evacuation.

Learning Point
Causes of delayed passage of meconium include:

• Mother treated with magnesium, other medications
• Prematurity due to immaturity of the intestinal motility
• Functional ileus due to infection (sepsis, pneumonia), electrolyte abnormalities
• Dysmotility including Hirschsprung disease
• Anatomic abnormalities – malpositioned anus, imperforate anus, intestinal atresia / web, duplications, fistula, cloacal malformation
• Malrotation or volvulus
• Cystic fibrosis – meconium ileus
• Hypothyroidism

Questions for Further Discussion
1. What are potential causes of abdominal distention? A review can be found here
2. What problems can meconium cause? A review can be found here
3. What are potential causes of constipation? A review can be found here

Related Cases

Disease: Delayed Passage of Meconium | Infant and Newborn Care | Constipation

Symptom/Presentation: Constipation and Encopresis

Specialty: Gastroenterology | Neonatology

Age: Newborn

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Common Infant and Newborn Problems and Intestinal Obstruction.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Clark DA. Times of First Void and First Stool in 500 Newborns. Pediatrics. 1977:60(4);457-59.

Karakus SC, Kilincaslan H, Sarsu SB, et al. The passage of meconium alone is not a sign of correctly positioned anus. The Journal of Maternal-Fetal & Neonatal Medicine. 2015;28(3):303-305. doi:10.3109/14767058.2014.916267

Gfroerer S, Rolle U. Pediatric intestinal motility disorders. World J Gastroenterol. 2015;21(33):9683-9687. doi:10.3748/wjg.v21.i33.9683

Mataya L, Lysouvakon P. Case 4: Delayed Passage of Meconium, Abdominal Distention, and Emesis in a 2-day-old Girl. Pediatrics In Review. 2019;40(6):310-312. doi:10.1542/pir.2017-0069

Lange M, Figura Y, Bohne C, Beske F, Bohnhorst B, Heep A. Management of prolonged meconium evacuation in preterm infants: A survey-based analysis in German Neonatal Intensive Care Units. Acta Paediatrica. 2022;111(11):2082-2089. doi:10.1111/apa.16528

Montalva L, Cheng LS, Kapur R, et al. Hirschsprung disease. Nat Rev Dis Primers. 2023;9(1):1-19. doi:10.1038/s41572-023-00465-y

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Patient Presentation
A 15 year old male came to clinic after a 1 week history of rhinorrhea and cough. He denied any fever, chills, nausea, or sore throat. He denied actual acute ear pain but said it felt fuller with pressure and was more difficult to hear from with his left ear. He had a history of seasonal allergic rhinitis during the fall and was not taking any of his medications at this time.

The pertinent physical exam showed a healthy male with normal vital signs and growth parameters. His nose had moderate clear rhinorrhea. His left ear had serous fluid with bubbles behind the tympanic membrane which was dull. There was no erythema or purulence noted. His right ear had only a small rim of serous fluid noted. The rest of his examination was normal.

The diagnosis of left sided serous otitis media was made and the natural history and symptomatic treatment were reviewed. He said, “It’s a good thing I don’t feel dizzy. I read a book about space flight and the first American in space was grounded for a while because he got hearing loss and dizziness. He got better too and went on one of the Apollo missions. He even golfed on the moon.” The pediatrician encouraged his reading and wish to possibly pursue an aerospace career.

Discussion
Meniere’s disease (MD) was described in 1861 by Dr. Prosper Meniere as an otologic balance disorder caused by semicircular canal problems. It is also known as endolymphatic hydrops.

MD causes vertigo, hearing loss, tinnitus and aural fullness. Usually, at least initially, the symptoms are unilateral. Attacks start suddenly and can last for 20 minutes to several hours. Its prevalence increases with age. It is more common in females than males (73-84 per 100,000 compared to 56 per 100,000 in the US). It is more common in Caucasians (91 per 100,000) and is more common in less populated areas such as the Midwest of the US.

Alan Shephard was the first American and second human in space in 1961. He was grounded for a period of time reportedly due to MD. He eventually was restored to flight status, and was crew commander for Apollo XIV. He loved to golf and therefore had a specially modified club to hit golf balls on the moon as well.

Learning Point
Although least common in the pediatric age range, MD does occur. Prevalence is estimated at 3 per 100,000. Vertigo occurs in children and benign paroxysmal positional vertigo and vestibular migraine account for the large majority of the patients. However there are several other entities that together account for 10-15% of the cases. MD in one study was the 3rd most common reason for vertigo/inner ear problem and accounted for 1.5% in a European study. Other literature estimates it at 0.4-2.9%.

MD and vestibular migraine can have similar symptoms. Attacks can last hours and be intermittent occurring over long time periods. Headache may not occur. Nystagmus may not be noted by caregivers and patients. Patients may also not be able to verbalize mild hearing loss/fullness or tinnitus. As it is difficult for children to describe their symptoms which may develop over long periods of time. One author “…suggested the young children with idiopathic recurrent vertiginous attacks of more than 20 min, accompanied by fluctuating low-tone hearing loss may have definite MD.”

Although some physical examination signs can be performed in the outpatient office, these are done infrequently and may not be performed in a standard manner or may not be able to be interpreted by a generalist physician. One example would be caloric testing. Patients may require other specialties (audiometry, otolaryngology, neurology) to more fully evaluate patients especially for differentiating among the various problems causing vertigo. Even more specialized testing may be needed including ocular or cervical vestibular evoked myogenic potentials. Additional testing may include causes of congenital hearing problems including syphilis, and MRI of the head to evaluate for embryopathic anomalies. Both pediatric and adult patients may be seen to show similar abnormal vestibular function, but adults have worse audiological function when diagnosed. Studies of pediatric MD have shown a genetic predisposition with 5-15% of patients having an autosomal dominant inheritance pattern. About 1/3 of pediatric patients have some type of positive family history. Over time the rates of bilateral disease in pediatric patients increases. There is no standardized treatment for pediatric MD but different treatments have been tried including diuretics anti-nausea, steroids and surgery.

Questions for Further Discussion
1. What causes vertigo in children? A review can be found here.
2. What are causes of ataxia? A review can be found here.
3. How common is syncope? A review can be found here.
4. What are some potential treatments for motion sickness? A review can be found here.

Related Cases

Disease: Acute Serous Otitis Media | Ear Disorders | Meniere’s Disease

Symptom/Presentation: Hearing Problem

Specialty: Medical History | Otolaryngology

Age: Teenager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Meniere’s Disease, Hearing Loss and Dizziness and Vertigo.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Simo H, Yang S, Qu W, Preis M, Nazzal M, Baugh R. Meniere’s disease: importance of socioeconomic and environmental factors. American Journal of Otolaryngology. 2015;36(3):393-398. doi:10.1016/j.amjoto.2015.01.009

Wang C, Wu CH, Cheng PW, Young YH. Pediatric Meniere’s disease. International Journal of Pediatric Otorhinolaryngology. 2018;105:16-19. doi:10.1016/j.ijporl.2017.11.029

Gedik-Soyuyuce O, Gence-Gumus Z, Ozdilek A, Ada M, Korkut N. Vestibular disorders in children: A retrospective analysis of vestibular function test findings. International Journal of Pediatric Otorhinolaryngology. 2021;146:110751. doi:10.1016/j.ijporl.2021.110751

Alan Shepard. In: Wikipedia. 2024. Accessed August 26, 2024. https://en.wikipedia.org/w/index.php?title=Alan_Shepard&oldid=1241612336

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa