bluuebunny/crossref_metadata_2025 huggingface dataset:
Trans-Kingdom Transposition of the Maize Dissociation Element
Authors: Emelyanov Alexander , Gao Yuan , Naqvi Naweed Isaak , Parinov Serguei
Published: September 2006

Transposons are very valuable tools for genetic manipulation. However, the number of transposable elements that have been suitably adapted for experimental use is insufficient and the spectrum of heterologous hosts in which they have been deployed is restricted. To date, only transposons from animal hosts have been utilized in heterologous animal species and transposons of plant origin have been used in plant genetics. There has been no experimental evidence that any of the known elements could transpose in hosts belonging to both kingdoms. Here we demonstrate that the maize Dissociation (Ds) element is capable of effective Activator (Ac) transposase-mediated transposition in the zebrafish Danio rerio, yielding remarkable germline transmission rates. In addition, mammalian cells were also found to be conducive to Ds transposition. Furthermore, we demonstrate that nuclear localization of Ac transposase is essential for genomic Ds transposition. Our results support the hypothesis that Ac/Ds elements do not rely on host-specific factors for transposition and that host factors involved in their mobility mechanism are widely conserved. Finally, even in vertebrate cells, the Ac/Ds system displays accurate transposition, large-fragment carrying capacity, high transposition frequencies, efficient germline transmission, and reporter gene expression, all of which are advantageous for various genetic applications and animal biotechnology.
Dynamical Analysis of the Regulatory Network Defining the Dorsal–Ventral Boundary of the Drosophila Wing Imaginal Disc
Authors: González Aitor , Chaouiya Claudine , Thieffry Denis
Published: September 2006

The larval development of the Drosophila melanogaster wings is organized by the protein Wingless, which is secreted by cells adjacent to the dorsal–ventral (DV) boundary. Two signaling processes acting between the second and early third instars and between the mid- and late third instar control the expression of Wingless in these boundary cells. Here, we integrate both signaling processes into a logical multivalued model encompassing four cells, i.e., a boundary and a flanking cell at each side of the boundary. Computer simulations of this model enable a qualitative reproduction of the main wild-type and mutant phenotypes described in the experimental literature. During the first signaling process, Notch becomes activated by the first signaling process in an Apterous-dependent manner. In silico perturbation experiments show that this early activation of Notch is unstable in the absence of Apterous. However, during the second signaling process, the Notch pattern becomes consolidated, and thus independent of Apterous, through activation of the paracrine positive feedback circuit of Wingless. Consequently, we propose that appropriate delays for Apterous inactivation and Wingless induction by Notch are crucial to maintain the wild-type expression at the dorsal–ventral boundary. Finally, another mutant simulation shows that cut expression might be shifted to late larval stages because of a potential interference with the early signaling process.
High Nucleotide Polymorphism and Rapid Decay of Linkage Disequilibrium in Wild Populations of Caenorhabditis remanei
Authors: Cutter Asher D , Baird Scott E , Charlesworth Deborah
Published: September 2006

The common ancestor of the self-fertilizing nematodes Caenorhabditis elegans and C. briggsae must have reproduced by obligate outcrossing, like most species in this genus. However, we have only a limited understanding about how genetic variation is patterned in such male–female (gonochoristic) Caenorhabditis species. Here, we report results from surveying nucleotide variation of six nuclear loci in a broad geographic sample of wild isolates of the gonochoristic C. remanei. We find high levels of diversity in this species, with silent-site diversity averaging 4.7%, implying an effective population size close to 1 million. Additionally, the pattern of polymorphisms reveals little evidence for population structure or deviation from neutral expectations, suggesting that the sampled C. remanei populations approximate panmixis and demographic equilibrium. Combined with the observation that linkage disequilibrium between pairs of polymorphic sites decays rapidly with distance, this suggests that C. remanei will provide an excellent system for identifying the genetic targets of natural selection from deviant patterns of polymorphism and linkage disequilibrium. The patterns revealed in this obligately outcrossing species may provide a useful model of the evolutionary circumstances in C. elegans' gonochoristic progenitor. This will be especially important if self-fertilization evolved recently in C. elegans history, because most of the evolutionary time separating C. elegans from its known relatives would have occurred in a state of obligate outcrossing.
Pronounced Differences of Recombination Activity at the Sex Determination Locus of the Honeybee, a Locus Under Strong Balancing Selection
Authors: Hasselmann Martin , Beye Martin
Published: September 2006

Recombination decreases the association of linked nucleotide sites and can influence levels of polymorphism in natural populations. When coupled with selection, recombination may relax potential conflict among linked genes, a concept that has played a central role in research on the evolution of recombination. The sex determination locus (SDL) of the honeybee is an informative example for exploring the combined forces of recombination, selection, and linkage on sequence evolution. Balancing selection at SDL is very strong and homozygous individuals at SDL are eliminated by worker bees. The recombination rate is increased up to four times that of the genomewide average in the region surrounding SDL. Analysis of nucleotide diversity (π) reveals a sevenfold increase of polymorphism within the sex determination gene complementary sex determiner (csd) that rapidly declines within 45 kb to levels of genomewide estimates. Although no recombination was observed within SDL, which contains csd, analyses of heterogeneity, shared polymorphic sites, and linkage disequilibrium (LD) show that recombination has contributed to the evolution of the 5′ part of some csd sequences. Gene conversion, however, has not obviously contributed to the evolution of csd sequences. The local control of recombination appears to be related to SDL function and mode of selection. The homogenizing force of recombination is reduced within SDL, which preserves allelic differences and specificity, while the increase of recombination activity around SDL relaxes conflict between SDL and linked genes.
Sequence Diversity, Reproductive Isolation and Species Concepts in Saccharomyces
Authors: Liti Gianni , Barton David B H , Louis Edward J
Published: September 2006

Using the biological species definition, yeasts of the genus Saccharomyces sensu stricto comprise six species and one natural hybrid. Previous work has shown that reproductive isolation between the species is due primarily to sequence divergence acted upon by the mismatch repair system and not due to major gene differences or chromosomal rearrangements. Sequence divergence through mismatch repair has also been shown to cause partial reproductive isolation among populations within a species. We have surveyed sequence variation in populations of Saccharomyces sensu stricto yeasts and measured meiotic sterility in hybrids. This allows us to determine the divergence necessary to produce the reproductive isolation seen among species. Rather than a sharp transition from fertility to sterility, which may have been expected, we find a smooth monotonic relationship between diversity and reproductive isolation, even as far as the well-accepted designations of S. paradoxus and S. cerevisiae as distinct species. Furthermore, we show that one species of Saccharomyces—S. cariocanus—differs from a population of S. paradoxus by four translocations, but not by sequence. There is molecular evidence of recent introgression from S. cerevisiae into the European population of S. paradoxus, supporting the idea that in nature the boundary between these species is fuzzy.
High-Resolution Quantitative Trait Locus Analysis Reveals Multiple Diabetes Susceptibility Loci Mapped to Intervals <800 kb in the Species-ConservedNiddm1iof the GK Rat
Authors: Granhall Charlotte , Park Hee-Bok , Fakhrai-Rad Hossein , Luthman Holger
Published: September 2006

Niddm1i, a 16-Mb locus within the major diabetes QTL in the diabetic GK rat, causes impaired glucose tolerance in the congenic NIDDM1I strain. Niddm1i is homologous to both human and mouse regions linked with type 2 diabetes susceptibility. We employed multiple QTL analyses of congenic F2 progeny selected for one recombination event within Niddm1i combined with characterization of subcongenic strains. Fine mapping located one hyperglycemia locus within 700 kb (Niddm1i4, P = 5 × 10−6). Two adjacent loci were also detected, and the GK allele at Niddm1i2 (500 kb) showed a glucose-raising effect, whereas it had a glucose-lowering effect at Niddm1i3 (400 kb). Most proximally, Niddm1i1 (800 kb) affecting body weight was identified. Experimental data from subcongenics supported the four loci. Sorcs1, one of the two known diabetes susceptibility genes in the region, resides within Niddm1i3, while Tcf7l2 maps outside all four loci. Multiple-marker QTL analysis incorporating the effect of cosegregating QTL as cofactors together with genetically selected progeny can remarkably enhance resolution of QTL. The data demonstrate that the species-conserved Niddm1i is a composite of at least four QTL affecting type 2 diabetes susceptibility and that two adjacent QTL (Niddm1i2GK and Niddm1i3GK) act in opposite directions.
Combining Bioinformatics and Phylogenetics to Identify Large Sets of Single-Copy Orthologous Genes (COSII) for Comparative, Evolutionary and Systematic Studies: A Test Case in the Euasterid Plant Clade
Authors: Wu Feinan , Mueller Lukas A , Crouzillat Dominique , Pétiard Vincent , Tanksley Steven D
Published: September 2006

We report herein the application of a set of algorithms to identify a large number (2869) of single-copy orthologs (COSII), which are shared by most, if not all, euasterid plant species as well as the model species Arabidopsis. Alignments of the orthologous sequences across multiple species enabled the design of “universal PCR primers,” which can be used to amplify the corresponding orthologs from a broad range of taxa, including those lacking any sequence databases. Functional annotation revealed that these conserved, single-copy orthologs encode a higher-than-expected frequency of proteins transported and utilized in organelles and a paucity of proteins associated with cell walls, protein kinases, transcription factors, and signal transduction. The enabling power of this new ortholog resource was demonstrated in phylogenetic studies, as well as in comparative mapping across the plant families tomato (family Solanaceae) and coffee (family Rubiaceae). The combined results of these studies provide compelling evidence that (1) the ancestral species that gave rise to the core euasterid families Solanaceae and Rubiaceae had a basic chromosome number of x = 11 or 12.2) No whole-genome duplication event (i.e., polyploidization) occurred immediately prior to or after the radiation of either Solanaceae or Rubiaceae as has been recently suggested.
Testing for Effects of Recombination Rate on Nucleotide Diversity in Natural Populations of Arabidopsis lyrata
Authors: Wright Stephen I , Foxe John Paul , DeRose-Wilson Leah , Kawabe Akira , Looseley Mark , Gaut Brandon S , Charlesworth Deborah
Published: September 2006

We investigated DNA sequence diversity for loci on chromosomes 1 and 2 in six natural populations of Arabidopsis lyrata and tested for the role of natural selection in structuring genomewide patterns of variability, specifically examining the effects of recombination rate on levels of silent polymorphism. In contrast with theoretical predictions from models of genetic hitchhiking, maximum-likelihood-based analyses of diversity and divergence do not suggest reduction of diversity in the region of suppressed recombination near the centromere of chromosome 1, except in a single population from Russia, in which the pericentromeric region may have undergone a local selective sweep or demographic process that reduced variability. We discuss various possibilities that might explain why nucleotide diversity in most A. lyrata populations is not related to recombination rate, including genic recombination hotspots, and low gene density in the low recombination rate region.
Doubly Uniparental Inheritance Is Associated With High Polymorphism for Rearranged and Recombinant Control Region Haplotypes in BalticMytilus trossulus
Authors: Burzyński Artur , Zbawicka Małgorzata , Skibinski David O F , Wenne Roman
Published: September 2006

Many bivalve species, including mussels of the genus Mytilus, are unusual in having two mtDNA genomes, one inherited maternally (the F genome) and the other inherited paternally (the M genome). The sequence differences between the genomes are usually great, indicating ancient divergence predating speciation events. However, in Mytilus trossulus from the Baltic, both genomes are similar to the F genome from the closely related M. edulis. This study analyzed the mtDNA control region structure in male and female Baltic M. trossulus mussels. We show that a great diversity of structural rearrangements is present in both sexes. Sperm samples are dominated by recombinant haplotypes with M. edulis M-like control region segments, some having large duplications. By contrast, the rearranged haplotypes that dominate in eggs lack segments from this M genome. The rearrangements can be explained by a combination of tandem duplication, deletion, and intermolecular recombination. An evolutionary pathway leading to the recombinant haplotypes is suggested. The data are also considered in relation to the hypothesis that the M. edulis M-like control region sequence is necessary to confer the paternal role on genomes that are otherwise F-like.
Mapping PrBn and Other Quantitative Trait Loci Responsible for the Control of Homeologous Chromosome Pairing in Oilseed Rape (Brassica napus L.) Haploids
Authors: Liu Zhiqian , Adamczyk Katarzyna , Manzanares-Dauleux Maria , Eber Frédérique , Lucas Marie-Odile , Delourme Régine , Chèvre Anne Marie , Jenczewski Eric
Published: September 2006

In allopolyploid species, fair meiosis could be challenged by homeologous chromosome pairing and is usually achieved by the action of homeologous pairing suppressor genes. Oilseed rape (Brassica napus) haploids (AC, n = 19) represent an attractive model for studying the mechanisms used by allopolyploids to ensure the diploid-like meiotic pairing pattern. In oilseed rape haploids, homeologous chromosome pairing at metaphase I was found to be genetically based and controlled by a major gene, PrBn, segregating in a background of polygenic variation. In this study, we have mapped PrBn within a 10-cM interval on the C genome linkage group DY15 and shown that PrBn displays incomplete penetrance or variable expressivity. We have identified three to six minor QTL/BTL that have slight additive effects on the amount of pairing at metaphase I but do not interact with PrBn. We have also detected a number of other loci that interact epistatically, notably with PrBn. Our results support the idea that, as in other polyploid species, metaphase I homeologous pairing in oilseed rape haploids is controlled by an integrated system of several genes, which function in a complex manner.
dSno Facilitates Baboon Signaling in the Drosophila Brain by Switching the Affinity of Medea Away From Mad and Toward dSmad2
Authors: Takaesu Norma T , Hyman-Walsh Cathy , Ye Ying , Wisotzkey Robert G , Stinchfield Michael J , O'Connor Michael B , Wotton David , Newfeld Stuart J
Published: September 2006

A screen for modifiers of Dpp adult phenotypes led to the identification of the Drosophila homolog of the Sno oncogene (dSno). The dSno locus is large, transcriptionally complex and contains a recent retrotransposon insertion that may be essential for dSno function, an intriguing possibility from the perspective of developmental evolution. dSno is highly transcribed in the embryonic central nervous system and transcripts are most abundant in third instar larvae. dSno mutant larvae have proliferation defects in the optic lobe of the brain very similar to those seen in baboon (Activin type I receptor) and dSmad2 mutants. This suggests that dSno is a mediator of Baboon signaling. dSno binds to Medea and Medea/dSno complexes have enhanced affinity for dSmad2. Alternatively, Medea/dSno complexes have reduced affinity for Mad such that, in the presence of dSno, Dpp signaling is antagonized. We propose that dSno functions as a switch in optic lobe development, shunting Medea from the Dpp pathway to the Activin pathway to ensure proper proliferation. Pathway switching in target cells is a previously unreported mechanism for regulating TGFβ signaling and a novel function for Sno/Ski family proteins.
Youth Tobacco Use: A Global Perspective for Child Health Care Clinicians
Authors: Prokhorov Alexander V. , Winickoff Jonathan P. , Ahluwalia Jasjit S. , Ossip-Klein Deborah , Tanski Susanne , Lando Harry A. , Moolchan Eric T. , Muramoto Myra , Klein Jonathan D. , Weitzman Michael , Ford Kentya H. ,   for the Tobacco Consortium, American Academy of Pediatrics Center for Child Health Research
Published: September 2006

Tobacco dependence, responsible for ∼4 million annual deaths worldwide, is considered to be a “pediatric disease.” The smoking epidemic is spreading rapidly in developing countries. Factors contributing to youth smoking in developing countries include cultural traditions, tobacco's easy accessibility and moderate pricing, peer and family influences, and tobacco companies' advertisements and promotional activities. Secondhand tobacco smoke exposure is a substantial problem that causes increased rates of pneumonia, otitis media, asthma, and other short- and long-term pediatric conditions. Parental tobacco use results in children's deprivation of essential needs such as nutrition and education. In this article we review contemporary evidence with respect to the etiology of nicotine dependence among youth, the forms of youth tobacco products worldwide, global youth tobacco-control efforts to date, medical education efforts, and child health care clinicians' special role in youth tobacco-control strategies. In addition, we provide a review of currently available funding opportunities for development and implementation of youth tobacco-control programs.
A National Survey of Terrorism Preparedness Training Among Pediatric, Family Practice, and Emergency Medicine Programs
Authors: Martin Shelly D. , Bush Anneke C. , Lynch Julia A.
Published: September 2006

OBJECTIVES. Domestic terrorism is a real threat focusing on a need to engage in effective emergency preparedness planning and training. Front-line physicians are an important component of any emergency preparedness plan. Potential victims of an attack include children who have unique physiologic and psychological vulnerabilities in disasters. Front-line providers need to have adequate training to effectively participate in local planning initiatives and to recognize and treat casualties including children. The goal of the survey was to assess the current state of terrorism preparedness training, including child victims, by emergency medicine, family practice, and pediatric residency programs in the United States and to assess methods of training and barriers to establishing effective training.

METHODS. A survey was e-mailed to a comprehensive list of all US pediatric, family practice, and emergency medicine residency programs 3 times between September 2003 and January 2004. The survey measured the perceived risk of terrorist attack, level of training by type of attack, level of training regarding children, method of training, and barriers to training.

RESULTS. Overall, 21% of programs responded (46 of 182 pediatric, 75 of 400 family practice, and 29 of 125 emergency medicine programs). Across all of the event types, emergency medicine programs were more likely to report adequate/comprehensive training. However, <50% of emergency medicine programs report adequate training for children. Didactic classroom-based lectures were the most commonly used method of training. Emergency medicine programs were more likely to use scenario-based exercises. Among programs that use scenario exercises, 93% report that they never (40%) or only sometimes (53%) incorporate child victims into the scenarios. Time, funding, access to subject matter experts, and availability of training material are the most important barriers to effective training.

CONCLUSIONS. Children are a precious national resource and a vulnerable population in disasters. Despite the availability of terrorism preparedness funding, these data suggest that we are failing to provide adequate training to front-line providers who may care for children in a catastrophic domestic terrorist event.
Expert Committee Recommendations for Acne Management
Authors: Zaenglein Andrea L. , Thiboutot Diane M.
Published: September 2006

In 2003, an international committee of physicians and researchers in the field of acne, working together as the Global Alliance to Improve Outcomes in Acne, developed consensus guidelines for the treatment of acne. These guidelines were evidence based when possible but also included the extensive clinical experience of this group of international dermatologists. As a result of the evaluation of available data and the experience, significant changes occurred in the management routines for acne. The greatest change arose on the basis of improved understanding of acne pathophysiology. The recommendation now is that acne treatments should be combined to target as many pathogenic factors as possible. A topical retinoid should be the foundation of treatment for most patients with acne, because retinoids target the microcomedo, the precursor to all acne lesions. Retinoids also are comedolytic and have intrinsic antiinflammatory effects, thus targeting 2 pathogenic factors in acne.Combining a topical retinoid with an antimicrobial agent targets 3 pathogenic factors, and clinical trials have shown that comination therapy results in significantly faster and greater clearing as opposed to antimicrobial therapy alone.Oral antibiotics should be used only in moderate-to-severe acne, should not be used as monotherapy, and should be discontinued as soon as possible (usually within 8–12 weeks).Because of their effect on the microcomedo, topical retinoids also are recommended as an important facet of maintenance therapy.
The Infant Development, Environment, and Lifestyle Study: Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Intrauterine Growth
Authors: Smith Lynne M. , LaGasse Linda L. , Derauf Chris , Grant Penny , Shah Rizwan , Arria Amelia , Huestis Marilyn , Haning William , Strauss Arthur , Grotta Sheri Della , Liu Jing , Lester Barry M.
Published: September 2006

OBJECTIVE. Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development, Environment and Lifestyle study.

DESIGN/METHOD. The Infant Development, Environment and Lifestyle study screened 13808 subjects at 4 clinical centers: 1618 were eligible and consented, among which 84 were methamphetamine exposed, and 1534 were unexposed. Those who were methamphetamine exposed were identified by self-report and/or gas chromatography-mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Those who were unexposed denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, or marijuana use, but excluded use of opiates, LSD, PCP or cocaine only. Neonatal parameters included birth weight and gestational age in weeks. One-way analysis of variance and linear-regression analyses were conducted on birth weight by exposure. The relationship of methamphetamine exposure and the incidence of small for gestational age was analyzed using multivariate logistic-regression analyses.

RESULTS. The methamphetamine exposed group was 3.5 times more likely to be small for gestational age than the unexposed group. Mothers who used tobacco during pregnancy were nearly 2 times more likely to have small-for-gestational-age infants. In addition, less maternal weight gain during pregnancy was more likely to result in a small-for-gestational-age infant. Birthweight in the methamphetamine exposed group was lower than the unexposed group.

CONCLUSIONS. These findings suggest that prenatal methamphetamine use is associated with fetal growth restriction after adjusting for covariates. Continued follow-up will determine if these infants are at increased risk for growth abnormalities in the future.
Why Are Latinos the Most Uninsured Racial/Ethnic Group of US Children? A Community-Based Study of Risk Factors for and Consequences of Being an Uninsured Latino Child
Authors: Flores Glenn , Abreu Milagros , Tomany-Korman Sandra C.
Published: September 2006

BACKGROUND. Latinos continue to be the most uninsured racial/ethnic group of US children, but not enough is known about the risk factors for and consequences of not being insured in Latino children.

OBJECTIVE. The objective of this study was to identify the risk factors for and consequences of being uninsured in Latino children.

METHODS. A cross-sectional survey was conducted of parents at urban, predominantly Latino community sites, including supermarkets, beauty salons, and laundromats. Parents were asked 76 questions on access and health insurance.

RESULTS. Interviews were conducted of 1100 parents, 900 of whom were Latino. Uninsured Latino children were significantly more likely than insured Latino children to be older (mean age: 9 vs 7 years) and poor (89% vs 72%) and to have parents who are limited in English proficiency (86% vs 65%), non-US citizens (87% vs 64%), and both employed (35% vs 27%). Uninsured Latinos were significantly less likely than their insured counterparts to have a regular physician (84% vs 99%) and significantly more likely not to be brought in for needed medical care because of expense, lack of insurance, difficulty making appointments, inconvenient office hours, and cultural issues. In multivariable analyses, parents who are undocumented or documented immigrants, both parents working, the child's age, and the $4000 to $9999 and $15000 to $19999 family income quintiles were the only factors that were significantly associated with a child's being uninsured; neither Latino ethnicity nor any other of 6 variables were associated with being uninsured. Compared with insured Latino children, uninsured Latino children had 23 times the odds of having no regular physician and were significantly more likely not to be brought in for needed medical care because of expense, lack of health insurance, difficulty making appointments, and cultural barriers.

CONCLUSIONS. After adjustment, parental noncitizenship, having 2 parents work, low family income, and older child age are associated with being an uninsured child, but Latino ethnicity is not. The higher prevalence of other risk factors seems to account for Latino children's high risk for being uninsured. Uninsured Latino children are significantly more likely than insured Latino children to have no regular physician and not to get needed medical care because of expense, lack of health insurance, difficulty making appointments, and cultural barriers. These findings indicate specific high-risk populations that might benefit most from targeted Medicaid and State Child Health Insurance Program outreach and enrollment efforts.
Morbidity and Mortality of Infants With Very Low Birth Weight in Japan: Center Variation
Authors: Kusuda Satoshi , Fujimura Masanori , Sakuma Izumi , Aotani Hirofumi , Kabe Kazuhiko , Itani Yasufumi , Ichiba Hiroyuki , Matsunami Katsura , Nishida Hiroshi ,   for the Neonatal Research Network, Japan
Published: September 2006

OBJECTIVES. The objectives of this study were to describe the characteristics and morbidity of very low birth weight infants, to identify the medical intervention for these infants, and to evaluate the factors affecting the mortality of these infants among the participating hospitals.

METHODS. A large multicenter neonatal research network that included level III NICUs from throughout Japan was established. A standardized mortality rate was formulated by giving a ratio of the observed deaths and the predicted deaths based on a 100-g birth weight interval mortality. A regression model was used to predict the factors that affect neonatal mortality.

RESULTS. The network included 37 centers and 2145 infants weighing ≤1500 g, born or admitted to the centers in 2003. Gestational age and birth weight of studied infants were 28.6 ± 3.6 gestational weeks (mean ± SD) and 1025 ± 302 g, respectively. Overall, 11% of the infants died before being discharged from hospitals (range: 0%–21%). The standardized mortality rate varied among the facilities (range: 0%–30%). No association between the annual number of patients admitted and standardized mortality rate was found. Among all of the very low birth weight infants, 14% were outborn infants, 72% were delivered by cesarean sections, 27% had patent ductus arteriosus, 3% had gastrointestinal perforation, 8% had bacterial sepsis, and 13% had intraventricular hemorrhage. Medical interventions involved were: 41% antenatal corticosteroids, 54% surfactant therapy, 18% postnatal steroids for chronic lung disease, and 29% high-frequency oscillatory ventilation. We found variations in the medical interventions and the clinical outcomes among the centers.

CONCLUSIONS. The overall survival rate for very low birth weight infants among neonatal centers in Japan was ∼90%. However, differences in the morbidity and mortality were observed among these centers.
Long-term Follow-up of Swedish Children Vaccinated With Acellular Pertussis Vaccines at 3, 5, and 12 Months of Age Indicates the Need for a Booster Dose at 5 to 7 Years of Age
Authors: Gustafsson Lennart , Hessel Luc , Storsaeter Jann , Olin Patrick
Published: September 2006

OBJECTIVES. The purpose of this work was to evaluate the long-term effectiveness of vaccination with acellular pertussis vaccines at 3, 5, and 12 months of age.

METHODS. Clinical follow-up of reported culture- and polymerase chain reaction–confirmed cases of pertussis was initiated during October 1997 in most of Sweden (except Gothenburg and environs). The study population included 90% of Swedish children born during 1996 or later (ie, who received diphtheria-tetanus-acellular pertussis vaccines at 3, 5, and 12 months of age) and children who had participated in a large pertussis vaccine trial in 1993–1996. Age-specific incidences were estimated using reported culture- or polymerase chain reaction–confirmed pertussis from October 1997 to September 2004 in areas covered by enhanced surveillance. In addition, annual overall and age-specific incidences of pertussis throughout Sweden before and after introduction of acellular pertussis vaccines were estimated.

RESULTS. The overall incidence of notified culture- and polymerase chain reaction–confirmed pertussis dropped from 113 to 150 per 100 000 during 1992–1995 to 11 to 16 per 100 000 during 2001–2004. In areas of enhanced surveillance, the incidence of pertussis was 31 per 100 000 person-years after 2 doses and 19 per 100 000 person-years after the third dose at 12 months of age. The age-specific incidence remained low for ∼5 years after the third dose but increased in children aged 6 to 8 years, becoming 32 and 48 per 100 000 person-years, respectively. The highest incidence occurred among infants who were unvaccinated or had received only 1 dose of diphtheria-tetanus-acellular pertussis vaccine.

CONCLUSIONS. The increased incidence among 7- to 8-year-olds (ie, mainly acellular pertussis vaccine–vaccinated children) suggests waning of vaccine-induced protection from pertussis. Along with a concomitant increase in incidence among infants, most likely infected by older siblings, these data suggest a booster dose of acellular pertussis vaccine is warranted from 5 to 7 years of age.
Hospitalizations of Newborns With Folate-Sensitive Birth Defects Before and After Fortification of Foods With Folic Acid
Authors: Robbins James M. , Tilford John M. , Bird T.M. , Cleves Mario A. , Reading J. Alex , Hobbs Charlotte A.
Published: September 2006

CONTEXT. The prevalence of neural tube defects is reduced in populations of women who receive folic acid supplementation. Since 1998, grain products in the United States have been fortified with folic acid. Fortification may have additional benefits by reducing the national prevalence of newborn hospitalizations for other folate-sensitive birth defects.

OBJECTIVE. Our purpose with this work was to compare rates of hospitalizations of newborns with folate-sensitive birth defects before and after implementation of fortification of grains.

METHOD. National hospital discharge data from the Healthcare Cost and Utilization Project were used to compute rates of newborn hospitalizations for selected birth defects per 10000 live births in the United States. Newborn hospitalization rates involving congenital anomalies recognizable at birth were analyzed for 5 years before fortification of grains and 5 years after fortification. Additional analyses compared changes in newborn hospitalization rates for birth defects by race/ethnicity, income, insurance status, and region of the country.

RESULTS. Newborn hospitalization rates for spina bifida decreased 21% from 1993–1997 to 1998–2002. Newborn hospitalization rates also decreased for anencephaly (20%) and limb-reduction defects (4%). Decline in hospitalizations for spina bifida occurred more often among Hispanic newborns (33%) than among white (13%) or black (21%) newborns. Decline in limb-reduction defects was seen primarily among blacks (11%). Findings using hospitalization data were similar to recent reports using birth defect surveillance systems with the exception of findings for orofacial clefts and conotruncal heart defects. No reductions were noted in newborn hospitalizations for these anomalies.

CONCLUSIONS. Results from this ecological study fail to demonstrate substantial declines in newborn hospitalizations beyond those anticipated from a reduction in neural tube defects. The society-wide impact of the fortification program on birth defects and other health conditions should continue to be monitored.
Breastfeeding and Developmental Delay: Findings From the Millennium Cohort Study
Authors: Sacker Amanda , Quigley Maria A. , Kelly Yvonne J.
Published: September 2006

OBJECTIVE. We investigated whether the duration and exclusivity of breastfeeding affects the likelihood of gross and fine motor delay in infants and examined the effect of factors that might explain any observed differences.

METHODS. The study sample included all term singleton infants who weighed >2500 g at birth and were not placed in a special care infant unit and whose mothers participated in the first survey of the Millennium Cohort Study. Missing data reduced the sample to 14660 (94%) with complete data.

RESULTS. Almost half (47%) of the infants initially were exclusively breastfed, but only 3.5% of these infants were still being fed exclusively on breast milk after 4 months of age, and 34% of infants were not breastfed at all; 9% of the infants were identified with delays in gross motor coordination and 6% with fine motor coordination delays at age 9 months. The proportion of infants who mastered the developmental milestones increased with duration and exclusivity of breastfeeding. Infants who had never been breastfed were 50% more likely to have gross motor coordination delays than infants who had been breastfed exclusively for at least 4 months (10.7% vs 7.3%). Any breast milk also was positively related to development: infants who had never been breastfed were 30% more likely to have gross motor delays than infants who were given some breast milk for up to 2 months (10.7% vs 8.4%). The odds ratios for gross motor delay were not attenuated after adjustment for biological, socioeconomic, or psychosocial factors. Infants who were never breastfed had at least a 40% greater likelihood of fine motor delay than infants who were given breast milk for a prolonged period.

CONCLUSION. Our results suggest that the protective effect of breastfeeding on the attainment of gross motor milestones is attributable to some component(s) of breast milk or feature of breastfeeding and is not simply a product of advantaged social position, education, or parenting style, because control for these factors did not explain any of the observed association. In contrast, the association between breastfeeding and fine motor delay was explained by biological, socioeconomic, and psychosocial factors.
Family Physicians in the Child Health Care Workforce: Opportunities for Collaboration in Improving the Health of Children
Authors: Phillips Robert L. , Bazemore Andrew W. , Dodoo Martey S. , Shipman Scott A. , Green Larry A.
Published: September 2006

Pediatric workforce studies suggest that there may be a sufficient number of pediatricians for the current and projected US child population. These analyses do not fully consider the role of family medicine in the care of children. Family physicians provide 16% to 26% of visits for children, providing a medical home for one third of the child population, but face shrinking panels of children. Family medicine's role in children's health care is more stable in rural communities, for adolescents, and for underserved populations. For these populations, in particular, family medicine's role remains important. The erosion of the proportion of visits to family medicine is likely caused by the rapid rise in the number of pediatricians relative to a declining birth rate. Between 1981 and 2004, the general pediatrician population grew at 7 times the rate of the US population, and the family physician workforce grew at nearly 5 times the rate. The number of clinicians caring for children meets or exceeds most estimates of sufficiency; however, the workforce distribution is skewed, leaving certain populations and settings underserved. More than 5 million children and adolescents live in counties with no pediatrician. Unmet need, addressing health in the context of families and communities, and tackling “millennial morbidities” represent common ground for both specialties that could lead to specific, collaborative training, research, intervention, and advocacy.
Adverse Perinatal Outcomes and Risk for Postpartum Suicide Attempt in Washington State, 1987–2001
Authors: Schiff Melissa A. , Grossman David C.
Published: September 2006

OBJECTIVE. Postpartum suicide attempts are serious events with a significant impact on women and their families. Our objectives were to determine the temporal risk period for these events and to assess whether maternal complications and adverse infant outcomes are associated with risk for postpartum suicide attempt.

METHODS. We performed a case-control study that compared 520 women who were hospitalized for a postpartum suicide attempt with 2204 control women who were not hospitalized for a postpartum suicide attempt in Washington State from 1987 to 2001. We performed logistic regression to evaluate whether maternal complications and adverse infant outcome, after controlling for other risk factors, were associated with a hospitalization for a suicide attempt within 1 year after delivery.

RESULTS. Most attempts were the result of poisoning (63.6%). Suicide attempts were most frequent in the first and 12th months after delivery. Maternal complications including labor and delivery complications and cesarean delivery were not associated with risk for postpartum suicide attempt. After adjustment for age and marital status, fetal or infant death was associated with postpartum suicide attempt. Other adverse infant outcomes, including preterm delivery, low birth weight, and congenital malformations, were not associated with attempts.

CONCLUSIONS. Maternal complications were not associated with hospitalizations for suicide attempts in the year after delivery. However, fetal death or the death of an infant in the first year after delivery was strongly associated with hospitalization for a suicide attempt. These risk factors may be useful predictors for health care providers who care for women or children during the postpartum period.
Effect of Maternal Smoking During Pregnancy on Offspring's Cognitive Ability: Empirical Evidence for Complete Confounding in the US National Longitudinal Survey of Youth
Authors: Batty G. David , Der Geoff , Deary Ian J.
Published: September 2006

BACKGROUND. Numerous studies have reported that maternal cigarette smoking during pregnancy is related to lower IQ scores in the offspring. Confounding is a crucial issue in interpreting this association.

METHODS. In the US National Longitudinal Survey of Youth 1979, IQ was ascertained serially during childhood using the Peabody Individual Achievement Test, the total score for which comprises results on 3 subtests: mathematics, reading comprehension, and reading recognition. Maternal IQ was assessed by using the Armed Forces Qualification Test. There were 5578 offspring (born to 3145 mothers) with complete information for maternal smoking habits, total Peabody Individual Achievement Test score, and covariates.

RESULTS. The offspring of mothers who smoked ≥1 pack of cigarettes per day during pregnancy had an IQ score (Peabody Individual Achievement Test total) that was, on average, 2.87 points lower than children born to nonsmoking mothers. Separate control for maternal education (0.27-IQ-point decrement) and, to a lesser degree, maternal IQ (1.51-IQ-point decrement) led to marked attenuation of the maternal-smoking–offspring-IQ relation. A similar pattern of results was seen when Peabody Individual Achievement Test subtest results were the outcomes of interest. The only exception was the Peabody Individual Achievement Test mathematics score, in which adjusting for maternal IQ essentially led to complete attenuation of the maternal-smoking–offspring-IQ gradient (0.66-IQ-point decrement). The impact of controlling for physical, behavioral, and other social indices was much less pronounced than for maternal education or IQ.

CONCLUSIONS. These findings suggest that previous studies that did not adjust for maternal education and/or IQ may have overestimated the association of maternal smoking with offspring cognitive ability.
Pulmonary Nitric Oxide Synthases and Nitrotyrosine: Findings During Lung Development and in Chronic Lung Disease of Prematurity
Authors: Sheffield Mark , Mabry Sherry , Thibeault Donald W. , Truog William E.
Published: September 2006

BACKGROUND. Nitric oxide mediates and modulates pulmonary transition from fetal to postnatal life. NO is synthesized by 3 nitric oxide synthase isoforms. One key pathway of nitric oxide metabolism results in nitrotyrosine, a stable, measurable marker of nitric oxide production.

OBJECTIVE. The purpose of this study was to assess, by semiquantitative immunohistochemistry, nitric oxide synthase isoforms and nitrotyrosine at different airway and vascular tree levels in the lungs of neonates at different gestational ages and to compare results in control groups to those in infants with chronic lung disease.

DESIGN/METHODS. Formalin-fixed, paraffin-embedded, postmortem lung blocks were prepared for immunohistochemistry using antibodies to each nitric oxide synthase isoform and to nitrotyrosine. Blinded observers evaluated the airway and vascular trees for staining intensity (0–3 scale) at 5 levels and 3 levels, respectively. The control population consisted of infants from 22 to 42 weeks' gestation who died in <48 hours. Results were compared with gestation-matched infants with varying severity of chronic lung disease.

RESULTS. In control and chronic lung disease groups, 22 to 42 weeks' gestation, staining for all 3 of the nitric oxide synthase isoforms was found in the airway epithelium from the bronchus to the alveolus or distal-most airspace. The abundance or distribution of nitric oxide synthase-3 staining in the airways did not show significant correlation with gestational age or severity of chronic lung disease. In the vascular tree, intense nitric oxide synthase-3 and moderate nitric oxide synthase-2 staining was found; nitric oxide synthase-1 was not consistently stained. Nitrotyrosine did stain in the pulmonary tree. Compared with controls where nitrotyrosine staining was minimal, regardless of gestation, in infants with chronic lung disease there was more than fourfold increase between severe chronic lung disease (n = 12) and either mild chronic lung disease or control infants (n = 16).

CONCLUSIONS. All 3 of the nitric oxide synthase isoforms and nitrotyrosine are detectable by immunohistochemistry early in lung development. Nitric oxide synthase ontogeny shows no significant changes in abundance or distribution with advancing gestational age nor with chronic lung disease. Nitrotyrosine is significantly increased in severe chronic lung disease.
Immunosuppressive Therapy Does Not Prevent the Occurrence of Immunoglobulin E–Mediated Allergies in Children and Adolescents With Organ Transplants
Authors: Dehlink Eleonora , Gruber Saskia , Eiwegger Thomas , Gruber Diego , Mueller Thomas , Huber Wolf-Dietrich , Klepetko Walter , Rumpold Helmut , Urbanek Radvan , Szépfalusi Zsolt
Published: September 2006

BACKGROUND. Allogeneic organ transplantation has become a common procedure in acute and chronic organ failure. The major limitation, rejection of the allograft by the host's immune system, can be limited by various immunosuppressive drugs that target the adaptive T-cell response. Most of these drugs are used in the treatment of allergic diseases as well, suggesting that transplant recipients under long-term immunosuppressive therapy should not develop any sensitizations or at least not show any clinical signs of allergy. Surprisingly, organ-transplanted children and adults do report symptoms of type 1 allergies, such as allergic rhinoconjunctivitis, bronchial asthma, and food allergies. Thus far, mainly case reports and series on the occurrence of allergy after orthotopic liver transplantation exist.

OBJECTIVE. Our purpose with this study was to evaluate in a cross-sectional design the prevalence of immunoglobulin E-mediated sensitizations and type 1 allergies in solid organ–transplanted children and adolescents and to identify risk factors.

METHODS. Seventy-eight organ-transplanted subjects (50 kidney, 9 lung, 19 liver; mean age: 14.06 ± 5.94 years; range 1.42 to 24.25 years) were studied by standardized interviews (modified International Study of Asthma and Allergies in Childhood [ISAAC] criteria), skin-prick tests, and measurement of specific and total serum immunoglobulin E.

RESULTS. Nineteen patients (24.4%) were found to be sensitized to ≥1 common inhalant or food allergens, as reflected by elevated specific immunoglobulin E levels and/or positive skin-prick test results, and 8 subjects (10.3%) additionally reported a corresponding present history of atopic diseases. No severe anaphylactic reactions were reported. No statistically significant associations with gender, kind of transplanted organ, distinct immunosuppressive therapies, and age at time of transplantation or age at investigation were found (χ2 test, Fisher's exact test, and Wilcoxon rank-sum test, respectively). Multiple logistic-regression analysis did not identify any independent risk factor either.

CONCLUSION. This study demonstrates that therapeutic immunosuppression does not control sensitizations and clinical manifestation of type 1 allergies in organ-transplanted children and adolescents.