bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Marker for Purkinje Cells, KIAA0864 Protein. An Analysis Based on a Monoclonal Antibody HFB-16 in Developing Human Cerebellum
Authors: Nakamura Yasuhiro , Yamamoto Munehiko , Oda Eriko , Kanemura Yonehiro , Kodama Eri , Yamamoto Atsuyo , Yamamoto Hideyuki , Miyado Kenji , Okano Hirotaka James , Fukagawa Ryouji , Higaki Koichi , Yamasaki Mami , Okano Hideyuki
Published: April 2005

In the search for immunohistochemical markers of the developing human brain, a monoclonal antibody, HFB-16, was raised against homogenates from the cerebrum of a 15-gestational-week-old (GW) human fetus and screened on paraffin-embedded human embryonic brain specimens. This antibody was particularly useful as a marker for Purkinje cells in the developing human cerebellum. Positive immunoreactivities with HFB-16 first appeared in the Purkinje cell layer at 17 GW. From 20 to 24 GW, positive immunoreactivities were found above the lamina dissecans. After 25 GW, dendrites of Purkinje cells were found with the HFB-16 antibody, and the nerve fibers of the Purkinje cells became positive after 35 GW. Neurons in the dentate nucleus and external and internal granular layers reacted negatively to this antibody. After 1 year, when the external granular layer faded out, the dendrites of the Purkinje cells reached the pial surface of the cerebellum, and nerve fibers began to develop in the white matter. This antibody was also useful for characterization of components in heterotopic neurons found in various anomaly syndromes such as trisomy 13. Expressional cloning indicated the antigen against HFB-16 to be human KIAA0864 protein, which is supposed to be an alternative splicing product of p116Rip, whose function has not yet been elucidated. The antigenicity of the KIAA0864 protein was confirmed using human cDNA of the KIAA0864 protein, a protein expression vector, and an HFB-16 antibody.
The LIM Domain Protein Lmo4 Is Highly Expressed in Proliferating Mouse Epithelial Tissues
Authors: Sum Eleanor Y.M. , O'Reilly Lorraine A. , Jonas Nadeen , Lindeman Geoffrey J. , Visvader Jane E.
Published: April 2005

LMO4 belongs to the LIM-only family of zinc finger proteins that have been implicated in oncogenesis. The LMO4 gene is overexpressed in breast cancer and oral cavity carcinomas, and high levels of this protein inhibit mammary epithelial differentiation. Targeted deletion of Lmo4 in mice leads to complex phenotypic abnormalities and perinatal lethality. To further understand the role of LMO4, we have characterized Lmo4 expression in adult mouse tissues by immunohistochemical staining using monoclonal anti-Lmo4 antibodies. Lmo4 was highly expressed within specific cell types in diverse tissues. Expression was prevalent in epithelial-derived tissues, including the mammary gland, tongue, skin, small intestine, lung, and brain. High levels of Lmo4 were frequently observed in proliferating cells, such as the crypt cells of the small intestine and the basal cells of the skin and tongue. Lmo4 was highly expressed in the proliferative cap cell layer of the terminal end buds in the peripubertal mammary gland and in the lobuloalveolar units during pregnancy. The expression profile of Lmo4 suggests that this cofactor is an important regulator of epithelial proliferation and has implications for its role in the pathogenicity of cancer.
NIR spectroscopic study of the complexation of neptunium(V) with humic acids: influence of phenolic OH groups on the complex formation
Authors: Sachs S. , Bernhard G.
Published: April 2005

The influence of phenolic OH groups on the Np(V) complexation by humic acids was studied at pH 7 and pH 8 under nitrogen atmosphere applying chemically modified humic acids with blocked phenolic OH groups in comparison to their corresponding unmodified humic acids. The studies were performed by near-infrared (NIR) absorption spectroscopy using the metal ion charge neutralization model for evaluation of the experimental data. For all humic acids under investigation comparable complexation constants were determined. However, the studied modified humic acids Aldrich and M42 show significantly lower loading capacities for NpO2+ions (e.g., pH 7: 7.2%±1.1% and 5.3%±1.0%, respectively) than the corresponding unmodified humic acids (e.g., pH 7: 10.0%±1.5 and 11.2%±1.1, respectively). This result points to a lower amount of maximal available humic acid ligand sites after blocking of phenolic OH groups. From that, it can be concluded that humic acid phenolic OH groups contribute to the interaction between humic acid and Np(V) under the studied conditions. The comparison of the loading capacities obtained for unmodified and modified Aldrich humic acid at pH 7 and pH 8 shows that the impact of phenolic OH groups on the Np(V) complexation by humic acids is increased with increasing pH value.
Development of quantitative analytical methods for the control of actinides in a pyrochemical partitioning process
Authors: Abousahl Said , van Belle P. , Eberle H. , Ottmar H. , Lynch B. , Vallet P. , Mayer K. , Ougier M.
Published: April 2005

Advanced nuclear fuel cycles are being developed in order to reduce the long-term radiotoxicity of highly radioactive waste. Pyrochemical partitioning techniques appear particularly attractive for advanced fuel cycles in which the minor actinides are recycled. The electrochemical processes of practical importance are the electrorefining process and the liquid–liquid extraction of transuranic (TRU) elements from fission products using either non-miscible molten metal or molten salt–metal phases. Analytical methods for the accurate assay of actinide elements in these matrices needed to be developed. A quantitative assay is required in order to establish a material balance for process development and – at a later stage – for accountancy and control purposes. To this end radiometric techniques such as energy-dispersive X-ray fluorescence analysis (XRF), neutron coincidence counting (NCC) and high-resolution gamma spectrometry (HRGS) were extensively employed for the quantitative determination of actinides (U, Np, Pu, Am, Cm) in process samples. Comparative analyses were performed using inductively coupled plasma mass spectrometry (ICP-MS). The respective samples were available in small quantities (≅100 mg) either in the form of eutectic salt or in metallic form with Cd, Zr or Bi as major metallic matrix constituents.
Selection Theory for Marker-Assisted Backcrossing
Authors: Frisch Matthias , Melchinger Albrecht E
Published: April 2005

Marker-assisted backcrossing is routinely applied in breeding programs for gene introgression. While selection theory is the most important tool for the design of breeding programs for improvement of quantitative characters, no general selection theory is available for marker-assisted backcrossing. In this treatise, we develop a theory for marker-assisted selection for the proportion of the genome originating from the recurrent parent in a backcross program, carried out after preselection for the target gene(s). Our objectives were to (i) predict response to selection and (ii) give criteria for selecting the most promising backcross individuals for further backcrossing or selfing. Prediction of response to selection is based on the marker linkage map and the marker genotype of the parent(s) of the backcross population. In comparison to standard normal distribution selection theory, the main advantage of our approach is that it considers the reduction of the variance in the donor genome proportion due to selection. The developed selection criteria take into account the marker genotype of the candidates and consider whether these will be used for selfing or backcrossing. Prediction of response to selection is illustrated for model genomes of maize and sugar beet. Selection of promising individuals is illustrated with experimental data from sugar beet. The presented approach can assist geneticists and breeders in the efficient design of gene introgression programs.
A General Framework for Statistical Linkage Analysis in Multivalent Tetraploids
Authors: Wu Rongling , Ma Chang-Xing
Published: April 2005

In multivalent polyploids, simultaneous pairings among homologous chromosomes at meiosis result in a unique cytological phenomenon—double reduction. Double reduction casts an impact on chromosome evolution in higher plants, but because of its confounded effect on the pattern of gene cosegregation, it complicates linkage analysis and map construction with polymorphic molecular markers. In this article, we have proposed a general statistical model for simultaneously estimating the frequencies of double reduction, the recombination fraction, and optimal parental linkage phases between any types of markers, both fully and partially informative, or dominant and codominant, for a tetraploid species that undergoes only multivalent pairing. This model provides an in-depth extension of our earlier linkage model that was built upon Fisher's classifications for different gamete formation modes during the polysomic inheritance of a multivalent polyploid. By implementing a two-stage hierarchical EM algorithm, we derived a closed-form solution for estimating the frequencies of double reduction through the estimation of gamete mode frequencies and the recombination fraction. We performed different settings of simulation studies to demonstrate the statistical properties of our model for estimating and testing double reduction and the linkage in multivalent tetraploids. As shown by a comparative analysis, our model provides a general framework that covers existing statistical approaches for linkage mapping in polyploids that are predominantly multivalent. The model will have great implications for understanding the genome structure and organization of polyploid species.
Using Drosophila to Decipher How Mutations Associated With Human Branchio-Oto-Renal Syndrome and Optical Defects Compromise the Protein Tyrosine Phosphatase and Transcriptional Functions of Eyes Absent
Authors: Mutsuddi Mousumi , Chaffee Benjamin , Cassidy Justin , Silver Serena J , Tootle Tina L , Rebay Ilaria
Published: April 2005

Eyes absent (EYA) proteins are defined by a conserved C-terminal EYA domain (ED) that both contributes to its function as a transcriptional coactivator by mediating protein-protein interactions and possesses intrinsic protein tyrosine phosphatase activity. Mutations in human EYA1 result in an autosomal dominant disorder called branchio-oto-renal (BOR) syndrome as well as congenital cataracts and ocular defects (OD). Both BOR- and OD-associated missense mutations alter residues in the conserved ED as do three missense mutations identified from Drosophila eya alleles. To investigate the molecular mechanisms whereby these mutations disrupt EYA function, we tested their activity in a series of assays that measured in vivo function, phosphatase activity, transcriptional capability, and protein-protein interactions. We find that the OD-associated mutations retain significant in vivo activity whereas those derived from BOR patients show a striking decrease or loss of in vivo functionality. Protein-protein interactions, either with its partner transcription factor Sine oculis or with EYA itself, were not significantly compromised. Finally, the results of the biochemical assays suggest that both loss of protein tyrosine phosphatase activity and reduced transcriptional capability contribute to the impaired EYA function associated with BOR/OD syndrome, thus shedding new light into the molecular mechanisms underlying this disease.
Dynein Promotes Achiasmate Segregation in Schizosaccharomyces pombe
Authors: Davis Luther , Smith Gerald R
Published: April 2005

Most organisms use crossovers (chiasmata) to maintain physical connections between homologous chromosomes that ensure their proper segregation at the first meiotic division. The fission yeast Schizosaccharomyces pombe has a residual ability to segregate homologous chromosomes in the absence of meiotic recombination (achiasmate segregation). Using cytologically tagged chromosomes, we established a role for the microtubule motor dynein in meiotic chromosome segregation. Dhc1, the motor subunit of dynein, is required for chromosome segregation in both the presence and the absence of recombination. Dlc1, a member of the Tctex-1 dynein light-chain family, preferentially affects the segregation of achiasmate chromosomes. Dlc1 is the first identified protein, outside of Drosophila, that preferentially affects achiasmate chromosome segregation. We discuss possible roles of the dynein motor in this process.
Sensitivity to Phosphonoacetic Acid
Authors: Li Lei , Murphy Kelly M , Kanevets Uliana , Reha-Krantz Linda J
Published: April 2005

A mutant allele (pol3-L612M) of the DNA polymerase δ gene in Saccharomyces cerevisiae that confers sensitivity to the antiviral drug phosphonoacetic acid (PAA) was constructed. We report that PAA-sensitivity tagging DNA polymerases is a useful method for selectively and reversibly inhibiting one type of DNA polymerase. Our initial studies reveal that replication by the L612M-DNA pol δ requires Rad27 flap endonuclease activity since the pol3-L612M strain is not viable in the absence of RAD27 function. The L612M-DNA pol δ also strongly depends on mismatch repair (MMR). Reduced viability is observed in the absence of any of the core MMR proteins—Msh2, Mlh1, or Pms1—and severe sensitivity to PAA is observed in the absence of the core proteins Msh6 or Exo1, but not Msh3. We propose that pol3-L612M cells need the Rad27 flap endonuclease and MMR complexes composed of Msh2/Msh6, Mlh1/Pms1, and Exo1 for correct processing of Okazaki fragments.
On the Mutation Rate of Herpes Simplex Virus Type 1
Authors: Drake John W , Hwang Charles B C
Published: April 2005

All seven DNA-based microbes for which carefully established mutation rates and mutational spectra were previously available displayed a genomic mutation rate in the neighborhood of 0.003 per chromosome replication. The pathogenic mammalian DNA virus herpes simplex type 1 has an estimated genomic mutation rate compatible with that value.
Spontaneous Mutations in the Ammonium Transport Gene AMT4 of Chlamydomonas reinhardtii
Authors: Kim Kwang-Seo , Feild Eithne , King Natalie , Yaoi Takuro , Kustu Sydney , Inwood William
Published: April 2005

Evidence in several microorganisms indicates that Amt proteins are gas channels for NH3 and CH3NH2, and this has been confirmed structurally. Chlamydomonas reinhardtii has at least four AMT genes, the most reported for a microorganism. Under nitrogen-limiting conditions all AMT genes are transcribed and Chlamydomonas is sensitive to methylammonium toxicity. All 16 spontaneous methylammonium-resistant mutants that we analyzed had defects in accumulation of [14C]methylammonium. Genetic crosses indicated that 12 had lesions in a single locus, whereas two each had lesions in other loci. Lesions in different loci were correlated with different degrees of defect in [14C]methylammonium uptake. One mutant in the largest class had an insert in the AMT4 gene, and the insert cosegregated with methylammonium resistance in genetic crosses. The other 11 strains in this class also had amt4 lesions, which we characterized at the molecular level. Properties of the amt4 mutants were clearly different from those of rh1 RNAi lines. They indicated that the physiological substrates for Amt and Rh proteins, the only two members of their protein superfamily, are NH3 and CO2, respectively.
Treatment of Childhood Constipation by Primary Care Physicians: Efficacy and Predictors of Outcome
Authors: Borowitz Stephen M. , Cox Daniel J. , Kovatchev Boris , Ritterband Lee M. , Sheen Jennifer , Sutphen James
Published: April 2005

Objective. Childhood constipation accounts for 3% of visits to general pediatric clinics and as many as 30% of visits to pediatric gastroenterologists. The majority of children who experience constipation and whose caregivers seek medical care are seen by primary care physicians such as pediatricians or family physicians. Little is known about how primary care physicians treat childhood constipation or the success of their treatments. With this study, we prospectively examined which treatments primary care physicians prescribe to children who present for the first time with constipation and how effective those treatments are.

Methods. A total of 119 children who were between 2 and 7 years of age (mean: 44.1 ± 13.6 months) and presented to 26 different primary care physicians (15 pediatricians and 11 family physicians) for the treatment of constipation for the first time participated in this study. Parents completed daily diaries of their child's bowel habits for 2 weeks before starting treatment recommended by their primary care physician and again 2 months after treatment. The prescribed treatment was identified by reviewing office records of the treating physicians.

Results. After 2 months of treatment, 44 (37%) of 119 children remained constipated. In the majority (87%) of cases, physicians prescribed some form of laxative or stool softener. The most commonly prescribed laxatives were magnesium hydroxide (77%), senna syrup (23%), mineral oil (8%), and lactulose (8%). In nearly all cases, a specific fixed dose of laxative was recommended; in only 5% of cases were parents instructed clearly to adjust the dose of laxative up or down to get the desired effect. In approximately half of the cases, physicians recommended some sort of dietary intervention. Some form of behavioral intervention was mentioned in the office records of approximately one third of cases; however, in most cases, little detail was provided. In 45% of cases, physicians prescribed disimpaction using oral cathartics, enemas, or suppositories followed by daily laxatives. In 35% of cases, physicians prescribed daily laxatives without any disimpaction procedure. In the remainder, physicians prescribed only dietary changes (5%), the use of intermittent laxatives (9%), or no therapy (7%). Treatment success corresponded to how aggressively the child was treated. Specifically, children who underwent some form of colonic evacuation followed by daily laxative therapy were more likely to have responded to treatment than were those who were treated less aggressively.

Conclusion. Primary care physicians tend to undertreat childhood constipation. After 2 months of treatment, nearly 40% of constipated children remain symptomatic.
Primary Hyperparathyroidism in Pediatric Patients
Authors: Kollars Josh , Zarroug Abdalla E. , van Heerden Jon , Lteif Aida , Stavlo Penny , Suarez Luis , Moir Christopher , Ishitani Michael , Rodeberg David
Published: April 2005

Objective. Primary hyperparathyroidism (HPT) is unusual in children. We reviewed our experience with HPT to better characterize these children.

Methods. The retrospective review of patients <19 years old who underwent parathyroid resection for primary HPT from 1970 to 2000 was performed at a single institution..

Results. Fifty-two patients were identified. Median age was 16.8 years (range: 4–18.9) with a female-to-male ratio of 3:2. Eighty-five percent had an elevated parathyroid hormone (PTH) level, and 15% had an inappropriately normal PTH level during hypercalcemia. Serum calcium was elevated in all patients except for 2 with multiple endocrine neoplasma (MEN)-IIA and 1 with familial non-MEN HPT, but both had elevated PTH levels. Alkaline phosphatase levels were significantly higher in children with documented bone involvement. At presentation 41 patients (79%) were symptomatic and end-organ damage (nephrocalcinosis, nephrolithiasis, acute pancreatitis, or bone involvement) occurred in 23 patients (44%). Thirty-four patients (65%) had a single adenoma; hyperplasia was identified in 16 patients (27%), and of these cases, 57% occurred in patients diagnosed with MEN-I. Short-term complications included transient hypocalcemia in 29 patients (56%) and transient vocal cord paralysis in 2 patients (4%). Long-term complications were significant for permanent hypocalcemia in 2 patients (4%) and no recurrent laryngeal nerve injuries. No parathyroid abnormalities were identified during exploration in 4 (8%) children. Long-term follow-up was achieved in 98% of patients for a mean and median of 13 years. Resolution of hypercalcemia was achieved in 94% of cases.

Conclusion. The diagnosis of primary HPT in pediatric patients is frequently delayed, is commonly symptomatic, and has significant morbidity. For children in whom HPT is suspected, evaluation of serum calcium and PTH levels is diagnostic in 100% of children. Parathyroid resection is effective at restoring normal serum calcium, has few complications, and is the treatment of choice for children with primary hyperparathyroidism.
Neonatal Ventilation With Inhaled Nitric Oxide Versus Ventilatory Support Without Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure: The INNOVO Multicentre Randomised Controlled Trial (ISRCTN 17821339)
Authors: Field D. , Elbourne D. , Truesdale A. , Grieve R. , Hardy P. , Fenton A.C. , Subhedar N. , Ahluwalia J. , Halliday H.L. , Stocks J. , Tomlin K. , Normand C. ,   on behalf of the INNOVO Trial Collaborating Group
Published: April 2005

Background. Although inhaled nitric oxide (iNO) may be a promising treatment for newborn infants with severe respiratory failure, the results from 3 previous small trials were inconclusive.

Methods. Infants of <34 weeks' gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomized to receive or not receive iNO. The study was not blinded.

Findings. Recruited were 108 infants (55 allocated to receive iNO and 53 not allocated to receive iNO) from 15 neonatal units in the United Kingdom and Republic of Ireland. Fifty-nine percent (64 of 108) died, and 84% of the survivors (37 of 44) had signs of some impairment or disability, 9 (20%) of them classified as severely disabled. There was no evidence of an effect of iNO on the primary outcomes: death or severe disability at 1 year corrected age (relative risk [RR]: 0.99; 95% confidence interval [CI]: 0.76 to 1.29); death or supplemental oxygen on expected date of delivery (RR: 0.84; 95% CI: 0.68 to 1.02); or death or supplemental oxygen at 36 weeks' postmenstrual age (RR: 0.98; 95% CI: 0.87 to 1.12). There was a trend for infants allocated to the iNO group to spend more time on the ventilator (log rank: 3.6), on supplemental oxygen (log rank: 1.4), and in hospital (log rank: 3.5) than those allocated to receive no iNO. This pattern predominantly reflected the infants who died. Mean total costs at 1 year corrected age were significantly higher in the iNO group, partly because of the costs of the gas but mainly because of the difference in initial hospitalization costs.

Interpretation. Evidence of prolongation of intensive care and increased costs of such care, without clear beneficial effects, implies that iNO cannot be recommended for preterm infants with severe hypoxic respiratory failure.
A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients
Authors: Pichichero Michael E.
Published: April 2005

The American Academy of Pediatrics, evidence-based guidelines endorse the use of cephalosporin antibiotics for patients with reported allergies to penicillin, for the treatment of acute bacterial sinusitis and acute otitis media. Many physicians, however, remain reluctant to prescribe such agents. Although such concern is understandable, lack of consistent data regarding exactly what constitutes an initial penicillin-allergic reaction and subsequent cross-sensitivity to cephalosporins may be preventing many patients from receiving optimal antibiotic therapy. This article reviews evidence in support of the American Academy of Pediatrics recommendation. Included is an examination of the types and incidence of reactions to penicillins and cephalosporins; the frequency of cross-reactivity between these 2 groups of agents; experimental and clinical studies that suggest that side chain-specific antibodies predominate in the immune response to cephalosporins, thereby explaining the lack of cross-sensitivity between most cephalosporins and penicillins; the role of skin testing; and the risks of anaphylaxis. Specific recommendations for the treatment of patients on the basis of their responses to previously prescribed agents are summarized.
Adult Health and Social Outcomes of Children Who Have Been in Public Care: Population-Based Study
Authors: Viner Russell M. , Taylor Brent
Published: April 2005

Objective. To examine adult socioeconomic, educational, social, and health outcomes of being in public care in childhood.

Methods. The 1970 British birth cohort was followed up at 5 (N = 13135), 10 (14875), 16 (11622), and 30 years (11261). Cases were defined as those ever in statutory or voluntary public care at 5, 10, and 16 years. Self-reported adult outcomes were occupation, educational achievement, general health, psychological morbidity, history of homelessness, school exclusion, and convictions.

Results. A total of 343 (3.6%) of 9557 had been in public care <17 years. Nonwhite children were more likely to have been in care (odds ratio [OR]: 3.3; 95% confidence interval [CI]: 2.1–5.4). Controlling for socioeconomic status, men with a history of public care were less likely to attain high social class (OR: 0.6; 95% CI: 0.4–0.9) and more likely to have been homeless (OR: 2.0; 95% CI: 1.1–3.8), have a conviction (OR: 2.3; 95% CI: 1.5–3.4), have psychological morbidity (OR: 1.8; 95% CI: 1.1–3.0), and be in poor general health (OR: 1.6; 95% CI: 1.1–2.6). Similar associations were found in women. Men but not women with a history of care were more likely to be unemployed (OR: 2.6; 95% CI: 1.4–5.0) and less likely to attain a higher degree (OR: 0.4; 95% CI: 0.2–0.7). Nonwhite ethnicity was associated with poorer adult outcomes of being in care.

Conclusions. Public care in childhood is associated with adverse adult socioeconomic, educational, legal, and health outcomes in excess of that associated with childhood or adult disadvantage.
Heart Rate Characteristics and Laboratory Tests in Neonatal Sepsis
Authors: Griffin M. Pamela , Lake Douglas E. , Moorman J. Randall
Published: April 2005

Objective. The evaluation of an infant for suspected sepsis often includes obtaining blood for laboratory tests. The shortcomings of the current practice are that the infant has to appear clinically ill for the diagnosis to be entertained, and the conventional laboratory tests are invasive. We have found that the clinical diagnosis of neonatal sepsis is preceded by abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations, and we have devised a predictive HRC monitoring strategy based on multivariable logistic regression analysis that was developed at one tertiary care NICU and validated at another. We hypothesized that HRC monitoring, which is continuous and noninvasive, might be an adjunct to conventional laboratory tests in the diagnosis of neonatal sepsis. The objective of this study was to test the hypothesis that HRC monitoring adds information to conventional laboratory tests in diagnosing neonatal sepsis.

Methods. We prospectively collected heart rate data in 678 consecutive infants who stayed >7 days in the University of Virginia NICU from July 1999 to July 2003. We prospectively measured HRC and noted 149 episodes of sepsis with positive blood cultures for which data were available in 137. We obtained all laboratory test results for ratio of immature to total neutrophil count, white blood cell count, glucose, platelet count, HCO3, arterial partial pressure of carbon dioxide, and pH. We tested hypotheses using multivariable logistic regression modeling adjusted for repeated measures.

Results. We found that the HRC index, which was available 92% of the time, was highly significantly associated with sepsis (receiver-operating characteristic [ROC] area: 0.73). The ratio of immature to total neutrophil count, white blood cell count (available 4%–8% of the time, usually around the time of suspected sepsis), and blood glucose and pH (available 28% and 38% of the time) were also significantly associated with sepsis (ROC area: 0.75). HRC and laboratory values added independent information to each other, and a predictive model using all significant variables had ROC area of 0.82.

Conclusions. HRC monitoring adds independent information to laboratory tests in the diagnosis of culture-positive neonatal sepsis.
Physician Reimbursement Levels and Adherence to American Academy of Pediatrics Well-Visit and Immunization Recommendations
Authors: McInerny Thomas K. , Cull William L. , Yudkowsky Beth K.
Published: April 2005

Background. There is concern that commercial health insurance reimbursement levels for immunizations and well-child visits may not be meeting the delivery and practice overhead costs within some areas of the country. There is also concern that insufficient physician reimbursement levels may negatively affect the quality of children’s health care.

Objective. We examined the relationships between commercial health insurance reimbursement levels to physicians for pediatric services and rates of immunization and well visits for children and adolescents.

Design. Quality of care was measured by examining state-level immunization and well-visit rates for 2002, which were obtained from the National Committee for Quality Assurance, Health Plan Employer Data and Information Set (HEDIS). Reimbursement data were obtained from the American Academy of Pediatrics Medical Cost Model. Variations in the child and adolescent HEDIS measures were examined as a function of physician reimbursement levels for pediatric services across states. HEDIS data were available for a total of 32 states. Partial correlations controlled for pediatrician concentration, as collected from the US Bureau of the Census and the American Medical Association Physician Masterfile data.

Results. Compliance with HEDIS immunization rates for all recommended vaccines was 60% for children and 24% for adolescents. By excluding the varicella vaccine, these rates increased to 70% for children and 44% for adolescents. Adherence rates for well visits were also higher for infants (60%) and children (59%) than for adolescents (34%). Physician reimbursement levels for pediatric services varied from $16.88 per member per month to $32.06 per member per month across states. Statistically significant positive correlations for reimbursement levels were found for 8 of the 16 HEDIS measures examined. Correlations with reimbursement levels were found for childhood immunizations (r = 0.42), infant well visits (r = 0.44), childhood well visits (r = 0.46), and adolescent well visits (r = 0.42). Reimbursement levels were especially strongly related to the rates of adolescent varicella vaccination (r = 0.53). When partial correlations were examined to control for pediatrician concentration, the correlations were reduced by 0.09 on average, suggesting that pediatrician supply may serve as an intermediary of the reimbursement relationship.

Conclusions. Immunization and well-visit rates for infants, children, and adolescents were positively linked with physician reimbursement rates for those services. Although methodologic limitations suggest caution when interpreting these findings, more attention should be given to physician reimbursement levels as a possible predictor of immunization and well-visit rates as measures of quality of care and to the importance of reimbursement levels for pediatrician recruitment.
Safety and Efficacy of the Nicotine Patch and Gum for the Treatment of Adolescent Tobacco Addiction
Authors: Moolchan Eric T. , Robinson Miqun L. , Ernst Monique , Cadet Jean Lud , Pickworth Wallace B. , Heishman Stephen J. , Schroeder Jennifer R.
Published: April 2005

Objectives. To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking.

Design. Double-blind, double-dummy, randomized, 3-arm trial with a nicotine patch (21 mg), nicotine gum (2 and 4 mg), or a placebo patch and gum; all participants received cognitive-behavioral group therapy.

Setting. Inner-city, outpatient clinic on the East Coast.

Subjects. Thirteen- to 17-year-old adolescents who smoked ≥10 cigarettes per day (CPD), scored ≥5 on the Fagerström Test of Nicotine Dependence, and were motivated to quit smoking.

Intervention. Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy, with a follow-up visit at 6 months (3 months after the end of treatment).

Main Outcome Measures. Safety assessed on the basis of adverse event reports for all 3 groups, prolonged abstinence, assessed through self-report and verified with exhaled carbon monoxide (CO) levels of ≤6 ppm, in intent-to-treat analyses, and smoking reduction (CPD and thiocyanate concentrations) among trial completers.

Results. A total of 120 participants were randomized (72% white, 70% female; age: 15.2 ± 1.33 years; smoking: 18.8 ± 8.56 CPD; Fagerström Test of Nicotine Dependence score: 7.04 ± 1.29) from 1999 to 2003. Participants started smoking at 11.2 ± 1.98 years of age and had been smoking daily for 2.66 ± 1.56 years; 75% had at least 1 current psychiatric diagnosis. Mean compliance across groups was higher for the patch (mean: 78.4–82.8%) than for the gum (mean: 38.5–50.7%). Both the patch and gum were well tolerated, and adverse events were similar to those reported in adult trials. Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant. Intent-to-treat analyses of all randomized participants showed CO-confirmed prolonged abstinence rates of 18% for the active-patch group, 6.5% for the active-gum group, and 2.5% for the placebo group; the difference between the active-patch and placebo arms was statistically significant. There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes. Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group. Mean smoking rates, but not CO or thiocyanate concentrations, decreased significantly in all 3 arms but not as a function of treatment group.

Conclusions. Nicotine patch therapy combined with cognitive-behavioral intervention was effective, compared with placebo, for treatment of tobacco dependence among adolescent smokers. Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking. Additional study of nicotine gum, with enhanced instructional support, is needed to assess its efficacy among adolescent smokers.
A National Survey of Pediatric Critical Care Resources in the United States
Authors: Odetola Folafoluwa O. , Clark Sarah J. , Freed Gary L. , Bratton Susan L. , Davis Matthew M.
Published: April 2005

Objective. To characterize resources available for the care of critically ill and injured children in the United States.

Study Design. In January through May 2004, we conducted a cross-sectional survey of medical directors of intensive care facilities for children.

Results. Pediatric critical care medical directors from 257 of 337 eligible hospitals responded to the survey (response rate: 76%). The median number of beds was 12 (interquartile range: 8–17 beds), with a median of 58 admissions per PICU bed (interquartile range: 44–70 admissions per PICU bed) in 2003. The median numbers of admissions per PICU bed were not statistically different among PICUs of different sizes. Fewer than 6% of hospitals shared PICU space with space for critically ill adults. The smallest units (1–6 beds) had higher physician and nurse staffing ratios per PICU bed. Advanced therapeutic technology, particularly renal replacement and inhaled nitric oxide therapy, was significantly more likely to be available in larger PICUs (≥7 beds).

Conclusions. PICUs with the fewest beds had higher physician and nurse staffing ratios per PICU bed and lower resource capacity for high-intensity renal and respiratory therapy. The impact of PICU resource availability on referral patterns and outcomes of pediatric critical illnesses warrants additional study.
Growth Hormone Therapy for Children Born Small for Gestational Age: Height Gain Is Less Dose Dependent Over the Long Term Than Over the Short Term
Authors: de Zegher Francis , Hokken-Koelega Anita
Published: April 2005

Background. Approximately 3% of children are born small for gestational age (SGA), and ∼10% of SGA children maintain a small body size throughout childhood and often into adult life. Among short SGA children, growth hormone (GH) therapy increases short-term growth in a dose-dependent manner; experience with long-term therapy is limited.

Objective. To delineate the dose dependency of long-term height gain among short SGA children receiving GH therapy.

Methods. We performed an epianalysis of the first adult height data for SGA children (n = 28) enrolled in 3 randomized trials comparing the growth-promoting efficacy of 2 continuous GH regimens (33 or 67 μg/kg per day for ∼10 years, starting at ∼5 years of age); in addition, we performed a meta-analysis of the adult height results published previously and those presented here.

Results. Epianalysis outcomes (n = 28) suggested that adult height increased more with a higher-dose regimen than with a lower-dose regimen. In the meta-analysis (n = 82), the higher-dose regimen was found to elicit a long-term height gain superior to that achieved with the lower-dose regimen by a mean of 0.4 SD (∼1 inch). Children who were shorter at the start of therapy experienced more long-term height gain.

Conclusions. These findings confirm GH therapy as an effective and safe approach to reduce the adult height deficit that short SGA children otherwise face. In addition, the first meta-analysis indicated that height gain is less dose dependent over the long term than over the short term, at least within the dose range explored to date. For SGA children whose stature is not extremely short, current data support the use of a GH dose of ∼33 μg/kg per day from start to adult height, particularly if treatment starts at a young age; shorter children (for example, height below −3 SD) might benefit from an approach in which short-term catch-up growth is achieved with a higher dose (≥50 μg/kg per day) and long-term growth to adult height is ensured with a GH dose of ∼33 μg/kg per day. Because GH-induced accelerations of height and weight gain evolve in parallel, the dose tapering from ≥50 μg/kg to ∼33 μg/kg can be accomplished by simply maintaining the absolute GH dose (in micrograms) while the child gains weight (in kilograms). With this algorithm, more growth-responsive children taper their GH dose down to ∼33 μg/kg per day more quickly.
High‐temperature oxidation of a metal particle: Nonisothermal model
Authors: Filimonov Igor , Luss Dan
Published: March 2005

A transient electric voltage of the order of 1 V may form during the combustion of a metal particle. The electrical field may form due to the different diffusion rate of the positive and negative charge carriers through a growing mixed‐ionic‐electronic conducting oxide shell. Unlike previous models, the effect of ambient gaseous oxygen transport to the particle surface is accounted for and steady‐state and charge neutrality in the oxide layer is not a priori assumed. Four key parameters affect the voltage‐temperature formation. The ratio between charge carries diffusion coefficients determines the surface electric potential amplitude, polarization and the time delay between the maximums of particle potential and temperature. The larger the difference between the diffusion coefficients, the greater is the voltage and the longer is the combustion time and the shorter is the time delay. The convection and radiation heat‐transfer coefficients exert a major impact on the time delay between the maximum of the surface electric potential and that of the temperature. The maximum electric potential and temperature are achieved almost at the same time when the transport coefficients are sufficiently large. This time difference decreases as either the heat‐transfer coefficients or the difference between the diffusion coefficients increase. Increasing the activation energy of the adsorption strongly decreased the oxidation, temperature and surface electric potential rate of rise during the early stage of the oxidation. Increasing the activation energy of the desorption increased the duration of the temperature and the potential drop in the later stage of the reaction. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Uncatalyzed and wall‐catalyzed forward water–gas shift reaction kinetics
Authors: Bustamante F. , Enick R. M. , Killmeyer R. P. , Howard B. H. , Rothenberger K. S. , Cugini A. V. , Morreale B. D. , Ciocco M. V.
Published: March 2005

The kinetics of the high‐temperature (1070–1134 K), low‐ and high‐pressure gas‐phase forward water–gas shift reaction (fWGSR) were evaluated in an empty quartz reactor and a quartz reactor packed with quartz particles. The power‐law expression for the reaction rate was consistent with the Bradford mechanism and was invariant with respect to pressure. The experimental rate constant was lower than that published by Graven and Long, and slightly higher than estimates obtained using the reaction rate expression derived from the Bradford mechanism in conjunction with values of reaction rate constants obtained from the GRI database. Similar experiments conducted using a reactor composed of Inconel® 600, a representative reactor shell material, exhibited substantially enhanced rates of reaction. A simple power‐law rate expression was incorporated into a surface‐catalyzed plug flow reactor (PFR) model to correlate the results between 600 and 900 K. Palladium and palladium–copper alloy surfaces, representative of hydrogen membranes, were also shown to enhance the fWGSR rate, but not as much as the Inconel® 600 surfaces. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Kinetic modeling of the reaction between hydrated lime and SO2 at low temperature
Authors: Bausach M. , Pera‐Titus M. , Fité C. , Cunill F. , Izquierdo J.‐F. , Tejero J. , Iborra M.
Published: March 2005

The kinetics of the noncatalytic solid–gas reaction between Ca(OH)2 and SO2 at low temperature and in the presence of water vapor was investigated. The effect of relative humidity, temperature, and SO2 concentration on the desulfurization capacity of the solid was evaluated, as well as the effect of NO2 concentration. A deactivation model (DM) and a new version of this model, by implementing an inverse shrinking core model (DM‐ISCM) with an ionic solid‐state diffusion control, were fitted to experimental kinetic data. The proposed model showed the best agreement with the experimental results. A chemical mechanism for the reaction on the solid surface was also discussed. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Flow maldistribution at bubble cap distributor in a plant‐scale circulating fluidized bed riser
Authors: Guo Qingjie , Werther Joachim , Aue‐Klett Cornelis , Hartge Ernst‐Ulrich
Published: March 2005

Flow maldistribution was investigated in an 8.5 m high circulating fluidized bed with a rectangular cross section of 1 × 0.3 m using a 14‐bubble‐cap distributor and a 33‐bubble‐cap distributor. Experimental results indicate that the bubble caps in the center region have a large flow rate and the bubble caps at the wall region have a small flow rate. The extent of the flow maldistribution is quantitatively characterized by the ratio of the maximum flow rate through a bubble cap to the average flow rate through all bubble caps (maldistribution number, Vmax/Vav). A correlation is proposed for predicting flow rate distribution, maldistribution number, in the bubble cap distributor by the ratio of distributor pressure drop to riser pressure drop (pressure‐drop ratio, ΔPd/ΔPr). © 2005 American Institute of Chemical Engineers AIChE J, 2005
Influence of plasma reactor structure on methanol oxidation
Authors: Yao S. , Zhang X. , Lu B.
Published: March 2005

Plasma oxidation of methanol (CH3OH) in oxygen and nitrogen was investigated using two dielectric barrier discharge (DBD) reactors with or without Al2O3 as a catalyst and using a DC circle‐to‐plate (CTP) reactor. An AC power supply was used for the DBD reactors to generate corona discharges. A DC power supply, a 20‐MΩ resistor, and a 100‐pF capacitor were used to yield pulselike discharges. CH3OH was oxidized to formaldehyde (HCHO), carbon monoxide (CO), and carbon dioxide (CO2). HCHO was the main product when using DBD reactors and without Al2O3. CO was the main product when using the DBD reactor with Al2O3 and CTP reactor. Al2O3 could inhibit CH3OH further oxidation. The energy efficiency of the DBD reactors decreased with increasing power input and power density. The energy efficiency of the CTP reactor peaked with 7 g CH3OH/kWh that was three times as high as that with the DBD reactors at the same power input. Furthermore, the power density of the CTP reactor was higher than that of the DBD reactors, implying that the CTP reactor could be used for CH3OH oxidation with a small discharge space volume. © 2005 American Institute of Chemical Engineers AIChE J, 2005
Molecular genetic confirmatory testing from newborn screening samples for the common African‐American, Asian Indian, Southeast Asian, and Chinese β‐thalassemia mutations
Authors: Bhardwaj Urvashi , Zhang Yao‐Hua , Lorey Fred , McCabe Linda L. , McCabe Edward R.B.
Published: March 2005

β‐Thalassemia is a serious health problem in the United States, especially in California, due to increased Asian immigration. Neonatal screening by using high‐performance liquid chromatography (HPLC) or isoelectric focusing (IEF) may lead to confusion due to interactions of various hemoglobinopathies with β‐thalassemia. Our purpose was to develop single‐tube multiplexed PCR assays using original neonatal screening specimens to identify the mutations responsible for β‐thalassemia in order to expedite diagnostic confirmation. Primers were designed for two to six common ethnic‐specific mutations using the amplification refractory mutation system (ARMS). This multiplex ARMS approach was standardized using DNA samples with known mutations for β‐thalassemia in those of Asian (Southeast Asian, Chinese, and Asian Indian) and African‐American descent. Specimens from African‐American neonates were tested for two mutations (−88 and −29); Asian Indians for five mutations (IVSI‐1, IVSI‐5, codons (Cd) 41/42, Cd 8/9, and 619‐bp deletion); Chinese, Taiwanese, and Southeast Asians for seven mutations (Cd 41/42, Cd 17, −28, IVSII‐654, Cd 71/72, IVSI‐5, and IVSI‐1). We identified each of these β‐thalassemia mutations in multiplexed ARMS from positive control samples. We tested 25 anonymized dried blood specimens from neonates who had been diagnosed with β‐thalassemia and who also belonged to these ethnic groups. We detected a mutation specific to the neonate's ethnic group using the ARMS approach in nearly all specimens, and the results were confirmed by sequencing. Multiplexed ARMS for ethnic‐specific β‐thalassemia mutations from the original newborn screening dried blood specimens is a rapid and efficient approach for diagnostic confirmation. Am. J. Hematol. 78:249–255, 2005. © 2005 Wiley‐Liss, Inc.