bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Response of a Pre-Stressed Transversely Isotropic Plate to Impact by an Elastic Rod
Authors: Rossikhin Yu A. , Shitikova M.V.
Published: December 2008

This article considers the problem of normal impact of a long thin elastic cylindrical rod upon an infinite pre-stressed elastic transversely isotropic plate possessing cylindrical anisotropy. The impact takes place at the center of the plate, whose equations of motion take both rotary inertia and shear deformations into account. During the shock interaction of the rod with the plate, waves with strong discontinuities are generated in the plate and begin to propagate. Behind the fronts of these waves, the solution is constructed in terms of ray series, the coefficients of which are the different order discontinuities in partial-time derivatives of the desired functions, and the time elapsed after the wave arrival at the point (of the plate) under consideration is a variable. The ray series coefficients are determined from recurrent equations within the accuracy of arbitrary constants, which are determined from the conditions of the dynamic contact interaction between the impactor and the target. These arbitrary constants allow one to construct the solution both within and outside the contact region. It is shown that as the radial compression forces reach a critical magnitude, the velocity and amplitude of the transient wave of transverse shear both diminish to zero. This leads us to the fact that the portion of the impact energy that is expended in work performed by transverse forces is completely absorbed at the contact spot, resulting in the occurrence of a damaged area within the contact region.
An Inverse Method to Assign Receptances by Using Classical Vibration Absorbers
Authors: Jianfeng Zhu  , Mottershead John E. , Kyprianou Andreas
Published: December 2008

The classical mass-spring absorber can be thought of as a very simple structural modification. In this paper the inverse problem of assigning receptances to a dynamic system by using one or more simple mass-spring absorbers is considered. The absorber parameters can be determined using selected receptances from the original system. When more than one absorber is applied, the equations that determine the modified-system receptances may be rearranged to form a set of nonlinear algebraic equations, multivariate polynomials in the absorber parameters. The desired absorber parameters are determined by the roots of these equations, which may be found by Newton's method or by using Gröbner bases. Realistic solutions require that positive values be found for the mass and stiffness of each of the added absorbers. Consequently there may be no acceptable solution, a unique solution, or there may be finitely many acceptable solutions. Whenever two receptances are to be assigned at a single frequency by a single absorber, then the available absorber mass and stiffness values are severely restricted. However, arbitrary assignment is possible for many other problems, except for the condition of positiveness on the masses and stiffnesses.
Interlaced Backstepping and Integrator Forwarding for Nonlinear Control of an Electrohydraulic Active Suspension
Authors: Kaddissi Claude , Saad Maarouf , Kenné Jean-Pierre
Published: December 2008

Passengers' comfort in long road trips is of crucial importance1 as a result, active suspension control became a vital subject in recent researches. This paper studies the control of an electrohydraulic active suspension, based on a combination of backstepping and integrator forwarding. Our goal is to control and reduce the car's vertical motion and keep it to zero. The active suspension model is highly nonlinear and nondifferentiable due to the hydraulic components, especially the servovalve and the hydraulic actuator whose chambers' volume varies during extension and retraction. Therefore, a powerful control strategy is required. In such cases, Lyapunov-based control strategies are the most suitable for offering a lot of maneuverability in building an analytical control signal. The mathematical model of an electrohydraulic active suspension can be classified among interlaced systems. This means that the state space model is a sequence of feedback and feedforward equations. Therefore, interlaced backstepping and integrator forwarding is an optimal control strategy to stabilize this class of systems, particularly electrohydraulic active suspension. Afterwards, we will introduce and define this constructive control method and its basis. The foremost advantage of this interlaced strategy is that, unlike others, it leaves no internal dynamic. This is a great relief in control issues, because an unstable internal dynamic will destabilize the whole system whatever control method is being used. As will be demonstrated, the interlaced backstepping and integrator forwarding is an outstanding control strategy to compensate the effect of chaotic roads on the stability of cars. The results are compared with a classic Proportional-Integral-Derivative regulator and a sliding mode controller, to show that the proposed controller outperforms a range of existing controllers for a range of perturbation signals.
Quantitative comparison of processes of oil- and water-based mud-filtrate invasion and corresponding effects on borehole resistivity measurements
Authors: Salazar Jesús M. , Torres-Verdín Carlos
Published: December 2008

Some laboratory and qualitative studies have documented the influence of water-based mud(WBM)-filtrate invasion on borehole resistivity measurements. Negligible work, however, has been devoted to studying the effects of oil-based mud(OBM)-filtrate invasion on well logs and the corresponding impact on the estimation of petrophysical properties. We quantitatively compare the effects of WBM- and OBM-filtrate invasion on borehole resistivity measurements. We simulate the process of mud-filtrate invasion into a porous and permeable rock formation assuming 1D radial distributions of fluid saturation and fluid properties while other petrophysical properties remain constant. To simulate the process of mud-filtrate invasion, we calculate a time-dependent flow rate of OBM-filtrate invasion by adapting the available formulation of the physics of WBM-filtrate invasion. This approach includes the dynamically coupled effects of mud-cake growth and multiphase filtrate invasion. Simulations are performed with a commercial adaptive-implicit compositional formulation that enables the quantification of effects caused by additional components of mud-filtrate and native fluids. The formation under analysis is 100% water saturated (base case) andis invaded with a single-component OBM. Subsequently, we perform simulations of WBM filtrate invading the same formation assuming that it is hydrocarbon bearing, and compare the results to those obtained in the presence of OBM. At the end of this process, we invoke Archie’s equation to calculate the radial distribution of electrical resistivity from the simulated radial distributions of water saturation and salt concentration and compare the effects of invasion on borehole resistivity measurements acquired in the presence of OBM and WBM. Simulations confirm that the flow rate of OBM-filtrate invasion remains controlled by the initial mud-cake permeability and formation petrophysical properties, specifically capillary pressure and relative permeability. Moreover, WBM causes radial lengths of invasion 15%–40% larger than those associated with OBM as observed on the radial distributions of electrical resistivity. It is found also that, in general, flow rates of WBM-filtrate invasion are higher than those of OBM-filtrate invasion caused by viscosity contrasts between OBM filtrate and native fluids, which slow down the process of invasion. Such a conclusion is validated by the marginal variability of array-induction resistivity measurements observed in simulations of OBM invasion compared with those of WBM invasion.
Adaptive multiple subtraction using regularized nonstationary regression
Authors: Fomel Sergey
Published: December 2008

Stationary regression is the backbone of seismic data-processing algorithms including match filtering, which is commonly applied for adaptive multiple subtraction. However, the assumption of stationarity is not always adequate for describing seismic signals. I have developed a general method of nonstationary regression and that applies to nonstationary match filtering. The key idea is the use of shaping regularization to constrain the variability of nonstationary regression coefficients. Simple computational experiments demonstrate advantages of shaping regularization over classic Tikhonov's regularization, including a more intuitive selection of parameters and a faster iterative convergence. Using benchmark synthetic data examples, I have successfully applied this method to the problem of adaptive subtraction of multiple reflections.
Severity of Vertebral Fractures Is Associated With Alterations of Cortical Architecture in Postmenopausal Women
Authors: Sornay-Rendu Elisabeth , Cabrera-Bravo Jose-Luis , Boutroy Stéphanie , Munoz Françoise , Delmas Pierre D
Published: December 2008

Patients with vertebral fractures (VFx) have trabecular architectural disruption on iliac biopsies. Because cortical bone is an important determinant of bone strength, we assessed cortical and trabecular microarchitecture at peripheral sites in patients with VFx of varying number (N) and severity (S). Bone architecture and volumetric density (vBMD) were assessed at the distal radius and tibia with HR-pQCT (XTreme CT; Scanco Medical, Bassersdorf, Switzerland) in 100 women with VFx (age, 74 ± 9 yr) of different S (GI, n = 23; GII, n = 35; GIII, n = 42) and in 362 women (age, 69 ± 7 yr) without peripheral or VFx (G0) from the OFELY study. Spine areal BMD (aBMD) was assessed by DXA. Among all women, at the radius and after adjustment for age and aBMD, there were significant trends in lower vBMD, cortical thickness (Cort.Th), trabecular number (Tb.N) and thickness (Tb.Th), higher trabecular separation (Tb.Sp), and distribution of separation (Tb.Sp.SD) with greater VFx S and N. Among women with VFx, lower Cort.Th and cortical vBMD (D.Cort) were associated with severe (GIII) and multiple (n > 2) VFx (p < 0.05). The age-adjusted OR for each SD decrease of Cort.Th was 2.04 (95% CI, 1.02–4.00) after adjustment for aBMD. At the tibia, there were trends for lower vBMD, Tb.N, Tb.Th, and higher Tb.Sp and Tb.Sp.SD with greater VFx S and N (p < 0.001). Among women with VFx, lower Cort.Th and D.Cort were associated with severe and multiple (n > 3) VFx (p < 0.01). In postmenopausal women, VFx are associated with low vBMD and architectural decay of trabecular and cortical bone at the radius and tibia, independently of spine aBMD. Severe and multiple VFx are associated with even more alterations of cortical bone.
Atp6v0d2 Is an Essential Component of the Osteoclast-Specific Proton Pump That Mediates Extracellular Acidification in Bone Resorption
Authors: Wu Haiping , Xu Guoliang , Li Yi-Ping
Published: December 2008

Bone resorption relies on the extracellular acidification function of vacuolar (V-) ATPase proton pump(s) present in the plasma membrane of osteoclasts. The exact configuration of osteoclast-specific V-ATPases remains largely unknown. In this study, we found that Atp6v0d2 (d2), an isoform of the d subunit in the V-ATPase, showed 5-fold higher expression than that of Atp6v0d1 (d1) in mature osteoclasts, indicating a potential function in osteoclastic bone resorption. When d2 was depleted at an early stage of RANKL-induced osteoclast differentiation in vitro, formation of multinucleated cells was severely impaired. However, depletion of d2 at a late differentiation stage did not affect osteoclast fusion but did abolish the activity of extracellular acidification and bone resorption of mature osteoclasts. We also showed the association of the two tagged-proteins d2 and a3 when co-expressed in mammalian cells with a co-immunoprecipitation assay. Moreover, glutathione-S-transferase (GST) pull-down assay showed the direct interaction of d2 with the N terminus of Atp6v0a3 (a3), which is the functionally identified osteoclast-specific component of V-ATPase. Therefore, our results show the dual function of d2 as a regulator of cell fusion in osteoclast differentiation and as an essential component of the osteoclast-specific proton pump that mediates extracellular acidification in bone resorption.
Dietary Calcium and Serum 25-Hydroxyvitamin D Status in Relation to BMD Among U.S. Adults
Authors: Bischoff-Ferrari Heike A , Kiel Douglas P , Dawson-Hughes Bess , Orav John E , Li Ruifeng , Spiegelman Donna , Dietrich Thomas , Willett Walter C
Published: December 2008

A higher calcium intake is still the primary recommendation for the prevention of osteoporosis, whereas vitamin D deficiency is often not addressed. To study the relative importance of dietary calcium intake and serum 25-hydroxyvitamin D [25(OH)D] status in regard to hip BMD, 4958 community-dwelling women and 5003 men ≥20 yr of age from the U.S. NHANES III population-based survey were studied. Calcium supplement users and individuals with a prior radius or hip fracture were excluded. We calculated standardized means for BMD by quartiles of sex-specific calcium intake for three 25(OH)D categories (<50, 50–74, and 75+ nM) among men and women, separately controlling for other important predictors of BMD. A higher calcium intake was significantly associated with higher BMD (p value for trend: p = 0.005) only for women with 25(OH)D status <50 nM, whereas calcium intake beyond the upper end of the lowest quartile (>566 mg/d) was not significantly associated with BMD at 25(OH)D concentrations >50 nM. Among men, there was no significant association between a higher calcium intake beyond the upper end of the lowest quartile (626 mg/d) and BMD within all 25(OH)D categories. Among both sexes, BMD increased stepwise and significantly with higher 25(OH)D concentrations (<50, 50–74, 75+ nM; p value for trend: women < 0.0001; men = 0.0001). Among men and women, 25(OH)D status seems to be the dominant predictor of BMD relative to calcium intake. Only women with 25(OH)D concentrations <50 nM seem to benefit from a higher calcium intake.
Risk Factors for Severity and Type of the Hip Fracture
Authors: Cauley Jane A , Lui Li-Yung , Genant Harry K , Salamone Loran , Browner Warren , Fink Howard A , Cohen Peter , Hillier Teresa , Bauer Doug C , Cummings Steven R
Published: December 2008

More severe hip fractures such as displaced femoral neck (FN) fractures and unstable intertrochanteric (IT) fractures lead to poorer outcomes, but risk factors for severe fractures have not been studied. To identify risk factors for severe types of hip fracture, we performed a prospective cohort study and obtained preoperative hip radiographs from women who sustained an incident hip fracture (excluding traumatic fractures). A single radiologist scored the severity of FN fractures by the Garden System: grades I and II, undisplaced; grades III and IV, displaced. The severity of IT hip fractures was rated by the Kyle System: grades I and II, stable; grades III and IV, unstable. A total of 249 women had FN fractures: 75 (30%) were undisplaced. A total of 213 women had IT fractures: 59 (28%) were stable. Both types of hip fracture increased with age, but older age was even more strongly associated with more severe hip fractures. Low BMD was more strongly related to undisplaced FN fractures (p interaction BMD × FN type, p = 0.0008) and stable IT fractures (p interaction BMD × IT type, p = 0.04). Similar findings were observed for estimated volumetric BMD and hip geometric parameters. Corticosteroid use was only associated with displaced FN fractures, and Parkinson's disease was only associated with stable IT fractures. Little difference was reported in the self-reported circumstances surrounding each type of fracture. In conclusion, the lower the BMD, the greater the likelihood of experiencing a hip fracture that is less displaced and more stable.
Positive Regulation of Adult Bone Formation by Osteoblast-Specific Transcription Factor Osterix
Authors: Baek Wook-Young , Lee Min-A , Jung Ji Won , Kim Shin-Yoon , Akiyama Haruhiko , de Crombrugghe Benoit , Kim Jung-Eun
Published: December 2008

Osterix (Osx) is essential for osteoblast differentiation and bone formation, because mice lacking Osx die within 1 h of birth with a complete absence of intramembranous and endochondral bone formation. Perinatal lethality caused by the disruption of the Osx gene prevents studies of the role of Osx in bones that are growing or already formed. Here, the function of Osx was examined in adult bones using the time- and site-specific Cre/loxP system. Osx was inactivated in all osteoblasts by Col1a1-Cre with the activity of Cre recombinase under the control of the 2.3-kb collagen promoter. Even though no bone defects were observed in newborn mice, Osx inactivation with 2.3-kb Col1a1-Cre exhibited osteopenia phenotypes in growing mice. BMD and bone-forming rate were decreased in lumbar vertebra, and the cortical bone of the long bones was thinner and more porous with reduced bone length. The trabecular bones were increased, but they were immature or premature. The expression of early marker genes for osteoblast differentiation such as Runx2, osteopontin, and alkaline phosphatase was markedly increased, but the late marker gene, osteocalcin, was decreased. However, no functional defects were found in osteoclasts. In summary, Osx inactivation in growing bones delayed osteoblast maturation, causing an accumulation of immature osteoblasts and reducing osteoblast function for bone formation, without apparent defects in bone resorption. These findings suggest a significant role of Osx in positively regulating osteoblast differentiation and bone formation in adult bone.
Atypical Femoral Fractures, Bisphosphonates, and Adult Hypophosphatasia
Authors: Whyte Michael P
Published: December 2008

Lateral subtrochanteric femoral pseudofractures occurring in adults with osteomalacia from hypophosphatasia and X-linked hypophosphatemia support the hypothesis that atypical femoral fractures in osteoporosis treated with bisphosphonates also result from low bone turnover.
Vitamin K Treatment Reduces Undercarboxylated Osteocalcin but Does Not Alter Bone Turnover, Density, or Geometry in Healthy Postmenopausal North American Women
Authors: Binkley Neil , Harke Judith , Krueger Diane , Engelke Jean , Vallarta-Ast Nellie , Gemar Dessa , Checovich Mary , Chappell Richard , Suttie John
Published: December 2008

Low vitamin K status is associated with low BMD and increased fracture risk. Additionally, a specific menaquinone, menatetrenone (MK4), may reduce fracture risk. However, whether vitamin K plays a role in the skeletal health of North American women remains unclear. Moreover, various K vitamers (e.g., phylloquinone and MK4) may have differing skeletal effects. The objective of this study was to evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal turnover and BMD in nonosteoporotic, postmenopausal, North American women. In this double-blind, placebo-controlled study, 381 postmenopausal women received phylloquinone (1 mg daily), MK4 (45 mg daily), or placebo for 12 mo. All participants received daily calcium and vitamin D3 supplementation. Serum bone-specific alkaline phosphatase (BSALP) and n-telopeptide of type 1 collagen (NTX) were measured at baseline and 1, 3, 6, and 12 mo. Lumbar spine and proximal femur BMD and proximal femur geometry were measured by DXA at baseline and 6 and 12 mo. At baseline, the three treatment groups did not differ in demographics or study endpoints. Compliance with calcium, phylloquinone, and MK4 treatment was 93%, 93%, and 87%, respectively. Phylloquinone and MK4 treatment reduced serum undercarboxylated osteocalcin but did not alter BSALP or NTX. No effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur geometric parameters was observed. This study does not support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal, North American women receiving calcium and vitamin D supplementation.
Serum Estradiol Is Associated With Volumetric BMD and Modulates the Impact of Physical Activity on Bone Size at the Age of Peak Bone Mass: A Study in Healthy Male Siblings
Authors: Lapauw Bruno M , Taes Youri , Bogaert Veerle , Vanbillemont Griet , Goemaere Stefan , Zmierczak Hans-Georg , De Bacquer Dirk , Kaufman Jean-Marc
Published: December 2008

This study investigates determinants of peak bone mass (PBM) in healthy men, focusing on effects and interactions of parameters reflecting mechanical loading and sex steroids. Healthy male siblings (n = 677; 25–45 yr) were recruited in a cross-sectional, population-based study. Physical activity score was assessed by a self-reported questionnaire. Cross-sectional muscle area (CSMA) and bone parameters of radius (4% and 66% site) and tibia (66% site) were assessed using pQCT. Peak torque of biceps and quadriceps muscles was assessed by isokinetic dynamometry. Serum testosterone (T) and estradiol (E2) levels were measured using immunoassays; free hormone fractions were calculated. Relations between indices of bone strength, CSMA, muscle strength, and sex steroids were studied using linear mixed-effects modeling. Physical activity, CSMA, and muscle strength were positively associated with indices of bone strength, except for volumetric BMD (vBMD). After controlling for age, weight, and height, free E2 levels were positively associated with trabecular and cortical vBMD, negatively associated with endosteal circumference at the radius, and positively associated with cortical vBMD at the tibia. In addition, positive interactions between physical activity and serum E2 concentrations were observed for bone size at the tibia. No associations between free T levels and pQCT bone parameters were found. In this population of healthy men at the age of PBM, parameters reflecting mechanical loading are confirmed as important determinants of bone size. E2, but not T, levels are positively associated with vBMD and modulate the impact of physical activity on bone size at the tibia.
Hypercalcemia and Overexpression of CYP27B1 in a Patient With Nephrogenic Systemic Fibrosis: Clinical Vignette and Literature Review
Authors: Pao Vivian Y , Chang Sandra , Shoback Dolores M , Bikle Daniel D
Published: December 2008

Nephrogenic systemic fibrosis (NSF) is a disease of thickened, hard, hyperpigmented skin lesions with or without systemic fibrosis occurring in patients with renal insufficiency and associated with the administration of gadolinium-containing contrast. The pathogenesis of this disease is unclear, and there is no definitive treatment. We describe a 71-yr-old patient with stable chronic lymphocytic leukemia (CLL), end-stage renal disease (ESRD), and NSF who presented with hypercalcemia in 2006. Before onset of renal insufficiency in 2002, serum calcium, phosphorus, and PTH levels were normal. In 2004, the patient began hemodialysis, and he was diagnosed with NSF in 2005, shortly after undergoing an MRI with gadolinium contrast administration. Over the next 6 mo, albumin-corrected serum total calcium levels rose from 9.9 to 13.1 mg/dl (normal range, 8.5–10.5 mg/dl) with normal serum phosphorus levels. On admission in September 2006, 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were elevated at 130.7 pg/ml (normal range, 25.1–66.1 pg/ml). Biopsy of an NSF lesion showed increased 25-hydroxyvitamin D3–1-α hydroxylase (CYP27B1) immunostaining compared with the biopsy from a normal control. This is the first reported association of NSF with hypercalcemia caused by elevated 1,25(OH)2D levels. This metabolic disturbance should be sought in future cases to determine a connection between NSF, 1,25(OH)2D metabolism, and CYP27B1 activation in the skin, which may shed light on the pathogenesis of this unusual local and systemic fibrosing disorder.
A Pilot Randomized, Controlled Trial of Later Treatment With a Peptide-Containing, Synthetic Surfactant for the Prevention of Bronchopulmonary Dysplasia
Authors: Laughon Matthew , Bose Carl , Moya Fernando , Aschner Judy , Donn Steven Mark , Morabito Christopher , Cummings James John , Segal Robert , Guardia Carlos , Liu Genzhou ,   for the Surfaxin Study Group
Published: December 2008

OBJECTIVE. Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bronchopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia.

METHODS. Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of ≥0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation.

RESULTS. Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64%) compared with the placebo group (39%); no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both lucinactant groups (33%) compared with the placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was 66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality.

CONCLUSIONS. There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of lucinactant, and this warrants further investigation.
Has Prenatal Screening Influenced the Prevalence of Comorbidities Associated With Down Syndrome and Subsequent Survival Rates?
Authors: Halliday Jane , Collins Veronica , Riley Merilyn , Youssef Danielle , Muggli Evelyne
Published: December 2008

OBJECTIVES. With this study we aimed to compare survival rates for children with Down syndrome in 2 time periods, 1 before prenatal screening (1988–1990) and 1 contemporaneous with screening (1998–2000), and to examine the frequency of comorbidities and their influence on survival rates.

METHODS. Record-linkage was performed between the population-based Victorian Birth Defects Register and records of deaths in children up to 15 years of age collected under the auspice of the Consultative Council on Obstetric and Pediatric Mortality and Morbidity. Cases of Down syndrome were coded according to the presence or absence of comorbidities by using the International Classification of Diseases, Ninth Revision classification of birth defects. Kaplan-Meier survival functions and log rank tests for equality of survival distributions were performed.

RESULTS. Of infants liveborn with Down syndrome in 1998–2000, 90% survived to 5 years of age, compared with 86% in the earlier cohort. With fetal deaths excluded, the proportion of isolated Down syndrome cases in the earlier cohort was 48.7% compared with 46.1% in the most recent cohort. In 1988–1990 there was at least 1 cardiac defect in 41.1% of cases and in 45.4% in 1998–2000. There was significant variation in survival rates for the different comorbidity groupings in the 1988–1990 cohort, but this was not so evident in the1998–2000 cohort.

CONCLUSIONS. Survival of children with Down syndrome continues to improve, and there is an overall survival figure of 90% to at least 5 years of age. It is clear from this study that prenatal screening technologies are not differentially ascertaining fetuses with Down syndrome and additional defects, because there has been no proportional increase in births of isolated cases with Down syndrome.
Attention-Deficit/Hyperactivity Disorder: How Much Responsibility Are Pediatricians Taking?
Authors: Stein Ruth E.K. , Horwitz Sarah McCue , Storfer-Isser Amy , Heneghan Amy M. , Hoagwood Kimberly Eaton , Kelleher Kelly J. , O'Connor Karen G. , Olson Lynn
Published: December 2008

BACKGROUND. Attention-deficit/hyperactivity disorder, the most common childhood behavioral condition, is one that pediatricians think they should identify and treat/manage.

OBJECTIVE. Our goals were to explore the relationships between pediatricians' self-reports of their practice behaviors concerning usually inquiring about and treating/managing attention-deficit/hyperactivity disorder and (1) attitudes regarding perceived responsibility for attention-deficit/hyperactivity disorder and (2) personal and practice characteristics.

METHODS. We analyzed data from the 59th Periodic Survey of the American Academy of Pediatrics for the 447 respondents who practice exclusively in general pediatrics. Bivariate and logistic regression analyses were used to identify attitudes and personal and practice characteristics associated with usually identifying and treating/managing attention-deficit/hyperactivity disorder.

RESULTS. A total of 67% reported that they usually inquire about and 65% reported that they usually treat/manage attention-deficit/hyperactivity disorder. Factors positively associated with usually inquiring about attention-deficit/hyperactivity disorder in adjusted multivariable analyses include perceived high prevalence among current patients, attendance at a lecture/conference on child mental health in the past 2 years, having patients who are assigned or can select a specific pediatrician, practicing in suburban communities, practicing for ≥10 years, and being female. Pediatricians' attitudes about responsibility for identification of attention-deficit/hyperactivity disorder were not associated with usually inquiring about attention-deficit/hyperactivity disorder in either unadjusted or adjusted analyses. Attitudes about treating/managing attention-deficit/hyperactivity disorder were significantly associated with usually treating/managing attention-deficit/hyperactivity disorder in unadjusted and adjusted analyses. Those who perceived that pediatricians should be responsible for treating/managing had almost 12 times the odds of reporting treating/managing attention-deficit/hyperactivity disorder, whereas those who believe physicians should refer had threefold decreased odds of treating/managing. Other physician/practice characteristics significantly associated with the odds of usually treating/managing attention-deficit/hyperactivity disorder include belief that attention-deficit/hyperactivity disorder is very prevalent among current patients, seeing patients who are assigned or can select a specific pediatrician, and practice location.

CONCLUSIONS. Taking responsibility for treating attention-deficit/hyperactivity disorder and practice characteristics seem to be important correlates of pediatrician self-reported behavior toward caring for children with attention-deficit/hyperactivity disorder.
Prolonged Duration of Initial Empirical Antibiotic Treatment Is Associated With Increased Rates of Necrotizing Enterocolitis and Death for Extremely Low Birth Weight Infants
Authors: Cotten C. Michael , Taylor Sarah , Stoll Barbara , Goldberg Ronald N. , Hansen Nellie I. , Sánchez Pablo J. , Ambalavanan Namasivayam , Benjamin Daniel K. ,   for the NICHD Neonatal Research Network
Published: December 2008

OBJECTIVES. Our objectives were to identify factors associated with the duration of the first antibiotic course initiated in the first 3 postnatal days and to assess associations between the duration of the initial antibiotic course and subsequent necrotizing enterocolitis or death in extremely low birth weight infants with sterile initial postnatal culture results.

METHODS. We conducted a retrospective cohort analysis of extremely low birth weight infants admitted to tertiary centers in 1998–2001. We defined initial empirical antibiotic treatment duration as continuous days of antibiotic therapy started in the first 3 postnatal days with sterile culture results. We used descriptive statistics to characterize center practice, bivariate analyses to identify factors associated with prolonged empirical antibiotic therapy (≥5 days), and multivariate analyses to evaluate associations between therapy duration, prolonged empirical therapy, and subsequent necrotizing enterocolitis or death.

RESULTS. Of 5693 extremely low birth weight infants admitted to 19 centers, 4039 (71%) survived >5 days, received initial empirical antibiotic treatment, and had sterile initial culture results through the first 3 postnatal days. The median therapy duration was 5 days (range: 1–36 days); 2147 infants (53%) received prolonged empirical therapy (center range: 27%–85%). Infants who received prolonged therapy were less mature, had lower Apgar scores, and were more likely to be black. In multivariate analyses adjusted for these factors and center, prolonged therapy was associated with increased odds of necrotizing enterocolitis or death and of death. Each empirical treatment day was associated with increased odds of death, necrotizing enterocolitis, and the composite measure of necrotizing enterocolitis or death.

CONCLUSION. Prolonged initial empirical antibiotic therapy may be associated with increased risk of necrotizing enterocolitis or death and should be used with caution.
Family Rejection as a Predictor of Negative Health Outcomes in White and Latino Lesbian, Gay, and Bisexual Young Adults
Authors: Ryan Caitlin , Huebner David , Diaz Rafael M. , Sanchez Jorge
Published: December 2008

OBJECTIVE. We examined specific family rejecting reactions to sexual orientation and gender expression during adolescence as predictors of current health problems in a sample of lesbian, gay, and bisexual young adults.

METHODS. On the basis of previously collected in-depth interviews, we developed quantitative scales to assess retrospectively in young adults the frequency of parental and caregiver reactions to a lesbian, gay, or bisexual sexual orientation during adolescence. Our survey instrument also included measures of 9 negative health indicators, including mental health, substance abuse, and sexual risk. The survey was administered to a sample of 224 white and Latino self-identified lesbian, gay, and bisexual young adults, aged 21 to 25, recruited through diverse venues and organizations. Participants completed self-report questionnaires by using either computer-assisted or pencil-and-paper surveys.

RESULTS. Higher rates of family rejection were significantly associated with poorer health outcomes. On the basis of odds ratios, lesbian, gay, and bisexual young adults who reported higher levels of family rejection during adolescence were 8.4 times more likely to report having attempted suicide, 5.9 times more likely to report high levels of depression, 3.4 times more likely to use illegal drugs, and 3.4 times more likely to report having engaged in unprotected sexual intercourse compared with peers from families that reported no or low levels of family rejection. Latino men reported the highest number of negative family reactions to their sexual orientation in adolescence.

CONCLUSIONS. This study establishes a clear link between specific parental and caregiver rejecting behaviors and negative health problems in young lesbian, gay, and bisexual adults. Providers who serve this population should assess and help educate families about the impact of rejecting behaviors. Counseling families, providing anticipatory guidance, and referring families for counseling and support can help make a critical difference in helping decrease risk and increasing well-being for lesbian, gay, and bisexual youth.
Effect of Bimonthly Supplementation With Oral Cholecalciferol on Serum 25-Hydroxyvitamin D Concentrations in HIV-Infected Children and Adolescents
Authors: Arpadi Stephen M. , McMahon Donald , Abrams Elaine J. , Bamji Marukh , Purswani Murli , Engelson Ellen S. , Horlick Mary , Shane Elizabeth
Published: December 2008

OBJECTIVE. Vitamin D insufficiency occurs commonly in HIV-infected youth in the United States. In light of the importance of vitamin D for skeletal and nonskeletal health, including innate immunity, developing methods for improving vitamin D status in HIV-infected children and adolescents is an important area of clinical research. The objective of this study was to evaluate the effect of administration of oral cholecalciferol, 100000 IU every 2 months, and 1 g/day calcium on serum 25-hydroxyvitamin D concentrations, serum and urine calcium, and HIV disease progression during a 12-month period.

METHODS. HIV-infected children and adolescents who were aged 6 to 16 years were randomly assigned to receive vitamin D (100000 IU bimonthly) and calcium (1 g/day; n = 29) or double placebo (n = 27). Serum 25-hydroxyvitamin D concentrations as measured by radioimmunoassay, albumin-corrected calcium concentrations, and spot urinary calcium-creatinine ratios were determined monthly.

RESULTS. No abnormalities in serum calcium concentration were observed. One participant who received placebo developed hypercalciuria. No group differences were seen in the change in CD4 count or CD4% or viral load during 12 months. The overall mean monthly serum 25-hydroxyvitamin D concentrations were higher in the group that received vitamin D and calcium than in the placebo group, as was the monthly serum 25-hydroxyvitamin D area under the curve. After completing 12 months of study, 2 (6.7%) participants in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration <20 ng/mL compared with 14 (50%) in the placebo group. Twelve (44.4%) in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration of ≥30 ng/mL compared with 3 (11.1%) in the placebo group.

CONCLUSIONS. Administration of oral cholecalciferol to HIV-infected children and adolescents at a dosage of 100000 IU every 2 months, together with 1 g/day calcium, is safe and results in significant increases in serum 25-hydroxyvitamin D concentrations.
Prevalence and Time Course of Acute Mountain Sickness in Older Children and Adolescents After Rapid Ascent to 3450 Meters
Authors: Bloch Jonathan , Duplain Hervé , Rimoldi Stefano F. , Stuber Thomas , Kriemler Susi , Allemann Yves , Sartori Claudio , Scherrer Urs
Published: December 2008

OBJECTIVE. Acute mountain sickness is a frequent and debilitating complication of high-altitude exposure, but there is little information on the prevalence and time course of acute mountain sickness in children and adolescents after rapid ascent by mechanical transportation to 3500 m, an altitude at which major tourist destinations are located throughout the world.

METHODS. We performed serial assessments of acute mountain sickness (Lake Louise scores) in 48 healthy nonacclimatized children and adolescents (mean ± SD age: 13.7 ± 0.3 years; 20 girls and 28 boys), with no previous high-altitude experience, 6, 18, and 42 hours after arrival at the Jungfraujoch high-altitude research station (3450 m), which was reached through a 2.5-hour train ascent.

RESULTS. We found that the overall prevalence of acute mountain sickness during the first 3 days at high altitude was 37.5%. Rates were similar for the 2 genders and decreased progressively during the stay (25% at 6 hours, 21% at 18 hours, and 8% at 42 hours). None of the subjects needed to be evacuated to lower altitude. Five subjects needed symptomatic treatment and responded well.

CONCLUSION. After rapid ascent to high altitude, the prevalence of acute mountain sickness in children and adolescents was relatively low; the clinical manifestations were benign and resolved rapidly. These findings suggest that, for the majority of healthy nonacclimatized children and adolescents, travel to 3500 m is safe and pharmacologic prophylaxis for acute mountain sickness is not needed.
Neurodevelopmental Outcome of Extremely Low Birth Weight Infants Randomly Assigned to Restrictive or Liberal Hemoglobin Thresholds for Blood Transfusion
Authors: Whyte Robin K. , Kirpalani Haresh , Asztalos Elizabeth V. , Andersen Chad , Blajchman Morris , Heddle Nancy , LaCorte Meena , Robertson Charlene M. T. , Clarke Maxine C. , Vincer Michael J. , Doyle Lex W. , Roberts Robin S. ,   for the PINTOS Study Group
Published: December 2008

BACKGROUND AND OBJECTIVE. Extremely low birth weight infants frequently receive red cell transfusions. We sought to determine whether a restrictive versus liberal hemoglobin transfusion threshold results in differences in death or adverse neurodevelopmental outcomes of extremely low birth weight infants.

PATIENTS AND METHODS. Extremely low birth weight infants previously enrolled in the Preterm Infants in Need of Transfusion Trial, a randomized, controlled trial of low versus high hemoglobin transfusion thresholds, were followed up at 18 to 21 months’ corrected age. Erythrocyte transfusion was determined by an algorithm of low (restrictive) or high (liberal) hemoglobin transfusion thresholds, differing by 10 to 20 g/L and maintained until first hospital discharge. The primary composite outcome was death or the presence of cerebral palsy, cognitive delay, or severe visual or hearing impairment.

RESULTS. Of 451 enrolled infants, the primary outcome was available in 430. There was no statistically significant difference in the primary outcome, found in 94 (45%) of 208 in the restrictive group and 82 (38%) of 213 in the liberal group. There were no statistically significant differences in preplanned secondary outcomes. However, the difference in cognitive delay (Mental Development Index score < 70) approached statistical significance. A posthoc analysis with cognitive delay redefined (Mental Development Index score < 85) showed a significant difference favoring the liberal threshold group.

CONCLUSIONS. Maintaining the hemoglobin of extremely low birth weight infants at these restrictive rather than liberal transfusion thresholds did not result in a statistically significant difference in combined death or severe adverse neurodevelopmental outcome.
Using a Count of Neonatal Morbidities to Predict Poor Outcome in Extremely Low Birth Weight Infants: Added Role of Neonatal Infection
Authors: Bassler Dirk , Stoll Barbara J. , Schmidt Barbara , Asztalos Elizabeth V. , Roberts Robin S. , Robertson Charlene M. T. , Sauve Reg S. ,   for the Trial of Indomethacin Prophylaxis in Preterms Investigators
Published: December 2008

OBJECTIVE. A count of 3 neonatal morbidities (bronchopulmonary dysplasia, brain injury, and severe retinopathy of prematurity) strongly predict the risk of death or neurosensory impairment in extremely low birth weight infants who survive to 36 weeks' postmenstrual age. Neonatal infection has also been linked with later impairment. We examined whether the addition of infection to the count of 3 neonatal morbidities further improves the prediction of poor outcome.

METHODS. We studied 944 infants who participated in the Trial of Indomethacin Prophylaxis in Preterms and survived to 36 weeks' postmenstrual age. Culture-proven sepsis, meningitis, and stage II or III necrotizing enterocolitis were recorded prospectively. We investigated the incremental prognostic importance of neonatal infection by adding terms for the different types of infection to a logistic model that already contained terms for the count of bronchopulmonary dysplasia, brain injury, and severe retinopathy. Poor outcome at 18 months of age was death or survival with 1 or more of the following: cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness.

RESULTS. There were 414 (44%) infants with at least 1 episode of infection or necrotizing enterocolitis. Meningitis and the presence of any type of infection added independent prognostic information to the morbidity-count model. The odds ratio associated with infection or necrotizing enterocolitis in this model was 50% smaller than the odds ratio associated with each count of the other 3 neonatal morbidities. Meningitis was rare and occurred in 22 (2.3%) of 944 infants.

CONCLUSIONS. In this cohort of extremely low birth weight infants who survived to 36 weeks' postmenstrual age, neonatal infection increased the risk of a late death or survival with neurosensory impairment. However, infection was a weaker predictor of poor outcome than bronchopulmonary dysplasia, brain injury, and severe retinopathy.
Family Burden After Traumatic Brain Injury in Children
Authors: Aitken Mary E. , McCarthy Melissa L. , Slomine Beth S. , Ding Ru , Durbin Dennis R. , Jaffe Kenneth M. , Paidas Charles N. , Dorsch Andrea M. , Christensen James R. , MacKenzie Ellen J. ,   and the CHAT Study Group
Published: December 2008

OBJECTIVE. Traumatic brain injury has a substantial impact on caregivers. This study describes the burden experienced by caregivers of children with traumatic brain injury and examines the relationship between child functioning and family burden during the first year after injury.

PATIENTS AND METHODS. Children aged 5 to 15 years hospitalized for traumatic brain injury at 4 participating trauma centers were eligible. Caregivers completed baseline and 3- and 12-month telephone interviews measuring the child's health-related quality of life using the Pediatric Quality of Life Inventory. The emotional impact scale of the Child Health Questionnaire was used to identify caregivers with substantial distress, including general worry or interference with family routine. Caregiver perceptions of whether health care needs were met or unmet and days missed from work were also measured.

RESULTS. A total of 330 subjects enrolled; follow-up was conducted with 312 at 3 months and 288 at 12 months. Most subjects were white (68%) and male (69%). Abnormal Pediatric Quality of Life Inventory subscores were related to substantial caregiver burden (either general worry or interference in routine). These abnormalities were reported by >75% of patients at 3 months and persisted to 1 year in some patients. Parental perception of unmet health care needs was strongly related to family burden outcomes, with up to 69% of this subset of parents reporting substantial worry, and nearly one quarter reporting interference with daily routine/concentration 1 year after injury. Child dysfunction predicted parental burden at 3 and 12 months. Burden was greater when health care need was unmet. Abnormalities on the Pediatric Quality of Life Inventory predicted the amount of work missed by parents, especially in the presence of unmet needs.

CONCLUSIONS. Caregivers are more likely to report family burden problems when child functioning is poorer and health care needs are unmet. Improved identification and provision of services is a potentially modifiable factor that may decrease family burden after pediatric traumatic brain injury.