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We present a finite deformation generalization of the finite thickness embedded discontinuity formulation presented in our previous paper [A.E. Huespe, A. Needleman, J. Oliver, P.J. Sánchez, A finite thickness band method for ductile fracture analysis, Int. J. Plasticity 25 (2009) 2349-2365]. In this framework the transition from a weak discontinuity to a strong discontinuity can occur using a single constitutive relation which is of importance in a range of applications, in particular ductile fracture, where localization typically precedes the creation of new free surface. An embedded weak discontinuity is introduced when the loss of ellipticity condition is met. The resulting localized deformation band is given a specified thickness which introduces a length scale thus providing a regularization of the post-localization response. The methodology is illustrated through several example problems emphasizing finite deformation effects including the development of a cup-cone failure in round bar tension. Fil: Huespe, Alfredo Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina Fil: Needleman, A.. University Of North Texas; Estados Unidos Fil: Oliver, J.. Technical University of Catalonia; España Fil: Sánchez, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Candidiasis carries a significant risk of death or neurodevelopmental impairment (NDI) in extremely low birth weight infants (ELBW;1000 g). We sought to determine the impact of candiduria in ELBW preterm infants.Our study was a secondary analysis of the Neonatal Research Network study Early Diagnosis of Nosocomial Candidiasis. Follow-up assessments included Bayley Scales of Infant Development examinations at 18-22 months of corrected age. Risk factors were compared between groups using exact tests and general linear modeling. Death, NDI, and death or NDI were compared using generalized linear mixed modeling.Of 1515 infants enrolled, 34 (2.2%) had candiduria only. Candida was isolated from blood only (69 of 1515 [4.6%]), cerebrospinal fluid (CSF) only (2 of 1515 [0.1%]), other sterile site only (not urine, blood, or CSF; 4 of 1515 [0.3%]), or multiple sources (28 of 1515 [2%]). Eleven infants had the same Candida species isolated in blood and urine within 3 days; 3 (27%) had a positive urine culture result first. Most urine isolates were Candida albicans (21 of 34 [62%]) or Candida parapsilosis (7 of 34 [29%]). Rate of death or NDI was greater among those with candiduria (50%) than among those with suspected but not proven infection (32%; odds ratio, 2.5 [95% confidence interval, 1.2-5.3]) after adjustment. No difference in death and death or NDI was noted between infants with candiduria and those with candidemia.These findings provide compelling evidence that ELBW infants with candiduria are at substantial risk of death or NDI. Candiduria in ELBW preterm infants should prompt a systemic evaluation (blood, CSF, and abdominal ultrasound) for disseminated Candida infection and warrants treatment.

Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease.We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy.A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09).Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).

Background: Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. Methods: Premature and term infants 4 mu g/mL for 50% of the dose interval and > 2 mu g/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5-148). Conclusions: Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.

To evaluate the repeatability of ocular aberrometry at distance and near vision conditions provided by the latest version of a ray tracing aberrometer.A total of 22 healthy eyes of 22 patients with ages ranging from 21 to 65 years were included in this study. All eyes achieved a best spectacle corrected visual acuity of 20/20, and had not undergone previous ocular surgeries. Three consecutive aberrometric measurements were obtained with the iTrace system (Tracey Technologies) by an experienced examiner at distance (5 m) and near (40 cm).Low values of within-subject standard deviation (Sw) were found for sphere and cylinder at distance and near and for the power vector components of refraction. However, a more pronounced variability was observed for the coefficients associated with higher order aberrations, with the poorest repeatability for the vertical coma at near, Sw of 0.011 μm for a mean value of 0.018 μm. Additionally, Sw for vertical coma was significantly larger at near (p = 0.01). No significant differences between the distance and near values of Sw for the power vector components of refraction were found (p ≥ 0.08). The Sw values for the distance and near modulation transfer function parameters were low when compared with their corresponding mean values.The iTrace system provides repeatable measurements of the spherocylindrical refraction at near and distance, but consistency of aberrometric and optical quality measurements seems to be limited.

Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives--real-time polymerase-chain-reaction (PCR)-based testing of a liquid-saliva or dried-saliva specimen obtained at birth--have been developed.In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth.A total of 177 of 34,989 infants (0.5%; 95% confidence interval [CI], 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively.Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.).

The use of herpes simplex virus (HSV) polymerase chain reaction for diagnosis of HSV disease involving the central nervous system has not translated into widespread use for the detection of DNAemia. We report our 6-year experience using blood polymerase chain reaction testing for HSV infection in neonates and older children with HSV disease.

To describe the clinical characteristics and outcomes of infants hospitalized at6 months of age with 2009 influenza A infection.Prospective laboratory surveillance and discharge International Classification of Disease, 9th edition codes for influenza infection were used to identify all infants hospitalized at6 months of age with positive influenza A tests at Children's Medical Center Dallas from April 27, 2009 to March 23, 2010. Retrospective chart review then was performed.Seventy-three infants aged6 months were hospitalized with laboratory-confirmed influenza A infection at a median age of 48 days (range, 3-179 days). The most common clinical characteristics were fever and respiratory signs, and 53% were given a bolus of intravenous fluid. Median length of hospitalization was 2 days (range, 1-162 days). Twenty (27%) infants developed influenza-related complications, including pneumonia (n = 3), hypoxia (n = 18), seizures (n = 2), need for intensive care (n = 8), or death (n = 2). Oseltamivir was administered to 60 (82%) infants and was well tolerated.The majority of infants hospitalized with 2009 influenza A had community-acquired infection that was associated with short hospital stays and favorable short-term outcomes. Complications including death occurred, emphasizing the need for preventive strategies.

Ureaplasma urealyticum is a common inhabitant of the urogenital tract of pregnant women. This mycoplasma is transmitted from a colonized woman to her newborn infant in one of three ways: (1) in utero either transplacentally from the mother's blood or by an ascending route secondary to colonization of the mother's urogenital tract; (2) at delivery by passage through a colonized birth canal; and (3) postnatally by horizontal or nosocomial transmission. The rate of vertical transmission ranges from 18% to 55% among full-term infants and from 29% to 55% among preterm infants. The rate of vertical transmission is not affected by method of delivery but is significantly increased when chorioamnionitis is present. Moreover, colonization of the infant with U. urealyticum occurs despite delivery by cesarean section with intact fetal membranes; ureaplasmal infection of the amniotic sac without rupture of membranes has been well described. Ultimately, the prevalence of infant colonization will depend on the prevalence of maternal colonization in a given population. However, the rate of colonization appears to be higher in very-low-birth-weight (VLBW) infants. Given this finding, as well as the potential for serious disease that could be attributed to U. urealyticum in this population, it seems reasonable to target the VLBW infant for a clinical treatment trial to determine if eradication of this organism will decrease the incidence of chronic lung disease.

OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22–28 weeks) and very low birth weight (401–1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS: Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at ≤12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified. CONCLUSION: Although the majority of infants with GAs of ≥24 weeks survive, high rates of morbidity among survivors continue to be observed.

OBJECTIVES: To determine the frequency of congenital cytomegalovirus (CMV) infection in infants born to human immunodeficiency virus (HIV)-infected mothers and assess risk factors that may facilitate intrauterine transmission of CMV, including the role of perinatal HIV infection. METHODS: Retrospective cohort study of infants who were born to HIV-infected mothers at Parkland Memorial Hospital and screened for congenital CMV infection according to a standard nursery protocol between February 1, 1997 and May 31, 2005. RESULTS: During the 8-year study period that included 125,781 live births, there were 367 infants (0.3%) born to 303 HIV-infected mothers. Of 333 HIV-exposed infants who were screened for CMV, 10 (3%) had congenital CMV infection and 6 (60%) of these were identified only because of the CMV screening protocol. Four (1%) infants were infected with HIV, and none of these was CMV-infected. Compared with CMV-uninfected infants, CMV-infected, HIV-exposed newborns had lower mean birth weight (2508 versus 3148 g, P < 0.01), lower gestational age (37 vs. 39 weeks, P < 0.01), and higher median maternal HIV viral load at the start of prenatal care (15,411 vs. 2209 copies/mL, P = 0.02). CMV-infected infants were more likely to be born to mothers who were diagnosed with HIV during the pregnancy or at delivery (P = 0.03). CONCLUSIONS: The prevalence of congenital CMV infection among HIV-exposed newborns was 3%. Screening of these infants for CMV would allow identification of infants who are at risk for delayed onset of hearing loss and other neurodevelopmental impairment.

In this contribution, a finite element methodology devised to simulate the structural deterioration of corroded reinforced concrete members is presented. The proposed numerical strategy has the ability to reproduce many of the well-known (undesirable) mechanical effects induced by corrosion processes in the embedded steel bars, as for example: expansion of the reinforcements due to the corrosion product accumulation, damage and cracking patterns distribution in the surrounding concrete, degradation of steel–concrete bond stress transfer, net area reduction in the reinforcements and, mainly, the influence of all these mentioned mechanisms on the structural load carrying capacity predictions. At the numerical level, each component of the RC structure is represented by means of a suitable FE formulation. For the concrete, a cohesive model based on the Continuum Strong Discontinuity Approach (CSDA) is used. Steel bars are modeled by means of an elasto-plastic constitutive relation. The interface is simulated using contact-friction elements, with the friction degradation as a function of the degree of corrosion attack. Two different (and coupled) mesoscopic analyzes are considered in order to describe the main physical phenomena that govern the problem: (i) an analysis at the cross section level and (ii) an analysis at the structural member level. The resultant mechanical model can be used to simulate generalized reinforcement corrosion. Experimental and previous numerical results, obtained from the available literature, are used to validate the proposed strategy. Financial support from the Spanish Ministry of Science and Technology trough grant BIA2005-09250-C03-03 and from ANPCyT of Argentina through grant PICT-2005- 34273, are gratefully acknowledged.

Neonatal neutropenia occurs in ∼50% of newborns delivered by women with pregnancy-induced hypertension. It is thought to be transient, independent of birth weight and gestational age, and unassociated with significant risks, including infection. It recently was suggested that neonatal neutropenia occurs primarily in smaller, younger neonates, is related to the severity of pregnancy-induced hypertension, and importantly, may be associated with an increased risk for nosocomial infection. We examined these points in a large inborn population in consecutive years, performing retrospective (n = 110, 1989) and prospective (n = 151, 1990) studies in low birth weight (≤2200 g) neonates delivered by women with pregnancy-induced hypertension. Overall, 40% to 50% of neonates studied developed neonatal neutropenia, and they were younger and smaller (P < .01) than non-neutropenic neonates. In the prospective study, neutropenic neonates were more likely to have mothers with severe pregnancy-induced hypertension (P < .001), and the incidence of neonatal neutropenia was primarily among neonates

Given the risk of central nervous system infection, relatively high weight-based echinocandin dosages may be required for the successful treatment of invasive candidiasis and candidemia in young infants. This open-label study assessed the safety and pharmacokinetics (PK) of micafungin in 13 young infants (48 h and120 days of life) with suspected candidemia or invasive candidiasis. Infants of body weightor =1,000 and1,000 g received 7 and 10 mg/kg/day, respectively, for a minimum of 4-5 days. In the 7-mg/kg/day group, the mean baseline weight and gestational age were 2,101 g and 30 weeks, respectively; in the 10-mg/kg/day group, they were 688 g and 25 weeks, respectively. The median pharmacokinetic values for the 7- and 10-mg/kg/day groups, respectively, were as follows: area under the concentration-time curve from 0 to 24 h (AUC(0-24)), 258.1 and 291.2 microg x h/ml; clearance at steady state adjusted for body weight, 0.45 and 0.57 ml/min/kg; maximum plasma concentration, 23.3 and 24.9 micro g/ml; and volume of distribution at steady state adjusted for body weight, 341.4 and 542.8 ml/kg. No deaths or discontinuations from treatment occurred. These data suggest that micafungin dosages of 7 and 10 mg/kg/day are well tolerated and provide exposure levels that have been shown (in animal models) to be adequate for central nervous system coverage.

Background Ganciclovir protects against hearing deterioration in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system (CNS). Objectives To assess the neurodevelopmental impact of ganciclovir therapy in this population. Study design 100 neonates were enrolled into a controlled Phase III study of symptomatic congenital CMV involving the CNS, and were randomized to either 6 weeks of intravenous ganciclovir or no treatment. Denver developmental tests were performed at 6 weeks, 6 months, and 12 months. For each age, developmental milestones that ≥90% of normal children would be expected to have achieved were identified. The numbers of milestones not met (“delays”) were determined for each subject. The average number of delays per subject was compared for each treatment group. Results At 6 months, the average number of delays was 4.46 and 7.51, respectively, for ganciclovir recipients and “no treatment” subjects ( p = 0.02). At 12 months, the average number of delays was 10.06 and 17.14, respectively ( p = 0.007). In a multivariate regression model, the effect of ganciclovir therapy remained statistically significant at 12 months ( p = 0.007). Conclusions Infants with symptomatic congenital CMV involving the CNS receiving intravenous ganciclovir therapy have fewer developmental delays at 6 and 12 months compared with untreated infants. Based on these data as well as the previously published data regarding ganciclovir treatment and hearing outcomes, 6 weeks of intravenous ganciclovir therapy can be considered in the management of babies with symptomatic congenital CMV disease involving the CNS. If treatment is initiated, it should be started within the first month of life and patients should be monitored closely for toxicity, especially neutropenia. Since existing data only address the treatment of symptomatic congenital CMV disease involving the CNS, these data cannot be extrapolated to neonates with other manifestations of CMV disease, including asymptomatic babies and symptomatic babies who do not have CNS involvement.

UNLABELLED Alternative antimicrobial regimens are needed for treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated pulmonary exacerbations in children with cystic fibrosis (CF). There are no published pharmacokinetic (PK) and pharmacodynamic (PD) data for linezolid in children with CF. OBJECTIVES (1) To determine the PK and PD profile of linezolid among children with CF; (2) to characterize the effect of linezolid on MRSA infection; (3) to determine the effect of age and CF transmembrane regulator (CFTR) gene mutations on drug clearance. HYPOTHESES Linezolid clearance is enhanced in children with CF requiring a higher dosage regimen. Age and CFTR gene mutations affect drug clearance. METHODS This was a retrospective cohort study; medical records of children with MRSA-associated pulmonary exacerbations treated with linezolid (10 mg/kg/dose IV every 8h) were reviewed. Linezolid peak and trough concentrations in serum were determined by high performance liquid chromatography, PK profiles determined using standard noncompartmental method, and PD indices were evaluated. RESULTS 10 children (mean +/- SD, 10.2 +/- 5.5 years) received 14 courses of linezolid at 10 +/- 0.4 mg/kg/dose every 8h for 15.4 +/- 3.2 days. Seven had homozygous DeltaF508 CFTR mutation. Peak and trough linezolid concentrations varied widely (range, 8.4-20.5 and 0.1-11.5 mcg/mL respectively). The PK profile of children or=10 years). The PK indices of children with homozygous DeltaF508 differed marginally from those with heterozygous CFTR mutations, but there were too few subjects to allow separation of age and CFTR mutations effect. No patient achieved the target PD ratio of AUC/MIC >80. MRSA persisted in sputum or throat culture after treatment with linezolid. CONCLUSIONS Additional PK and PD data are needed to optimize linezolid therapy in children with cystic fibrosis; it is likely that higher doses will be needed.

The diagnosis of congenital syphilis continues to pose a difficult clinical challenge. Because the serodiagnosis of congenital syphilis has significant limitations, the direct detection of Treponema pallidum in suspect neonatal tissues or body fluids represents a desirable alternate diagnostic strategy. We developed and applied the polymerase chain reaction (PCR) for the detection of T. pallidum in clinical material relevant to the diagnosis of congenital syphilis but which typically contain factors inhibitory for the PCR. Four methods of specimen processing were examined to circumvent PCR inhibition; clinical materials included amniotic fluids, neonatal sera, and neonatal cerebrospinal fluids. The PCR was 100% specific for T. T. pallidum compared with the sensitive rabbit infectivity test (RIT) for all clinical materials tested. For amniotic fluids, the PCR was 100% sensitive when correlated with the RIT but had a lesser sensitivity when applied to sera or cerebrospinal fluids, which typically contain few treponemes. The combined sensitivity of the PCR for all clinical samples was 78%. Positive PCR results also were obtained among some clinical specimens for which RIT was not performed; these results correlated well with either stigmata or risk factors for congenital syphilis. The combined results suggest that the PCR can be a useful adjunct to the diagnosis and clinical management of congenital syphilis and that it will provide a valuable tool for investigations of the pathogenesis of the disorder.

OBJECTIVES. The objectives were to determine the frequency of congenital cytomegalovirus infection among newborns who did not pass hearing screening tests or had confirmed hearing loss and to determine how often abnormal hearing screening results were the only manifestation of congenital cytomegalovirus infection.METHODS. Retrospective chart review was performed for newborns who had abnormal hearing screening results and positive urine cytomegalovirus culture results at Parkland Memorial Hospital between September 1, 1999, and August 31, 2004.RESULTS. During the 5-year study period, 572 of 79047 newborns (7 of 1000 live births) did not pass hearing screening tests. Cytomegalovirus infection was identified in 24 (5%) of 483 tested infants and 16 (6%) of the 256 infants with subsequently confirmed hearing impairment. Of those 16 infants, 12 (75%) were identified as having congenital cytomegalovirus infection only because of failure to pass newborn hearing screening tests.CONCLUSIONS. Congenital cytomegalovirus infection was present for 6% of newborns with confirmed hearing impairment, and the majority of those infants were identified on the basis of abnormal newborn hearing screening results.

Background. Intravenous ganciclovir administered for 6 weeks improves hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system. Methods. Twenty-four subjects received antiviral therapy for 6 weeks. Serial pharmacokinetic assessments were performed after administration ofvalganciclovir oral solution and of intravenous ganciclovir. Results. On the basis of a previous pharmacokinetic study of the use of intravenous ganciclovir in this population, a target AUC 12 (area under the concentration-time curve over a 12-h period) of 27 mg X h/L was defined. The median dose of oral valganciclovir administered in the present trial was 16 mg/kg, which produced a geometric mean AUC 12 of 27.4 mg X h/L. The bioavailability of valganciclovir was 41.1%. Of the 18 subjects who had detectable CMV in whole blood at baseline or during therapy, 11 had

In this work, we analyze some aspects of the macroscopic Gurson-Tvergaard-Needleman (GTN) constitutive model when it is addressed to solve ductile fracture problems by means of numerical simulations:(i) The analytical solutions of the material discontinuous bifurcation problem is performed.Closed and exact formulas are obtained. The so determined critical conditions and the developed strain localization mode are afterward studied and compared in crack growth problems. Even when this methodology of analysis is rather standard at the present, the conclusions drawn from this study differ significantly from that obtained with a similar analysis in quasi-brittle fracture problems.(ii) A new very robust numerical integration method for the GTN model, namely the Impl-Ex Method, is proposed. It is a low computational cost algorithm, equivalent to a linear problem per each integration step, with a reasonable precision for engineering purposes. Its accuracy and convergence rate is assessed by means of an error study applied to a ductile fracture test simulation.(iii) A detailed analysis of a plane strain ductile crack growth problem is performed in a material containing two size-scale of voids. In the analysis, particular attention is given to the mesh size dependence and to the coalescence of the larger void. Fil: Sánchez, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina Fil: Oliver, Juan Pablo. Technical University of Catalonia; España Fil: Huespe, Alfredo Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Clinical improvement is often delayed among children with invasive infections caused by multidrug resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) despite use of standard antimicrobial therapy. Daptomycin, a bactericidal lipopeptide antibiotic, may prove useful for treatment of these infections in children, but clinical experience is lacking.Retrospective review of medical records of hospitalized children who received daptomycin for treatment of invasive Gram-positive bacterial infections at Children's Medical Center Dallas from December 2003 to March 2007. Bacterial isolates were tested for susceptibility to daptomycin and characterized by pulsed-field gel electrophoresis and polymerase chain reaction for staphylococcal cassette chromosome mec A.Sixteen children (10 male; median age, 6.5 years) received daptomycin. Fifteen (94%) children had invasive staphylococcal disease (14, MRSA, of which 13 were community-associated; 1, methicillin-susceptible S. aureus), and 1 had urinary tract infection caused by VRE. Twelve children with disseminated staphylococcal disease had bacteremia for 2-10 days despite therapy with 2 or more of the following: vancomycin, clindamycin, rifampin, aminoglycoside, or linezolid. The addition of daptomycin resulted in bacteriologic cure in 6 of 7 evaluable patients with persistent bacteremia. No adverse events were attributed to daptomycin. Overall, 14 patients improved and were discharged home, and 2 died of complications of their underlying medical conditions.The majority of patients demonstrated clinical improvement after addition of daptomycin to conventional antimicrobial therapy. Further studies are needed to assess the pharmacokinetics, pharmacodynamics, safety, and effectiveness of daptomycin in infants and children.

Treatment options for primary cutaneous aspergillosis in neonates are limited by the lack of pharmacokinetic and safety data of newer antifungal agents that are effective against Aspergillus spp. We report the successful treatment of cutaneous aspergillosis in an extremely low-birth-weight preterm infant with liposomal amphotericin B, voriconazole and micafungin, and provide pharmacokinetic profiles for voriconazole and micafungin.

Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research-grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty-four neonates received 6 weeks of antiviral therapy. Ganciclovir and valganciclovir were measured by liquid chromatography/tandem mass spectroscopy. NONMEM version VI beta was used for population analyses. All profiles were consistent with a one-compartment model. Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 x body weight (WT)(1.68), 1.15 x WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial-grade valganciclovir oral solution may be a viable option for administration to neonates.

Although infections due to Staphylococcus aureus are infrequent in the neonatal intensive care unit (NICU), they are associated with substantial morbidity and mortality. In this issue of JAMA Pediatrics, Ericson et al1 describe a 15-year (1997-2012) retrospective study with invasive S aureus infections, defined as a positive culture of blood, cerebrospinal fluid, normally sterile body fluid, or abscess for S aureus, in 348 NICUs managed by the Pediatrix Medical Group. Among 887 910 infants admitted to these NICUs, 3888 (0.4%) had at least 1 invasive S aureus infection, which occurred in 2.2% of very low-birth-weight (VLBW) infants (birth weight

This retrospective study characterized the clinical course of 13 neonates who died with herpes simplex virus infection from 2001 to 2011, representing a 26% case-fatality rate. Fatal disease developed at ≤ 48 hours of age in one-third of infants, was mostly disseminated disease, and occurred despite early administration of high-dose acyclovir therapy.

A comparative study on finite elements for capturing strong discontinuities by means of elemental (E-FEM) or nodal enrichments (XFEM) is presented. Based on the same constitutive model (continuum damage) and linear elements (triangles and tetrahedra) optimized implementations of both types of enrichments in the same non-linear code are tested for a representative set of 2D and 3D crack propagation examples. It is shown that both methods provide the same qualitative and quantitative results for enough refined meshes. For the performed tests, E-FEM exhibited, in general, a higher accuracy, mostly for coarse meshes, whereas, convergence rate with mesh refinement, which is super-linear, showed slightly higher for X-FEM. As for the computational costs for single crack modelling X-FEM showed, depending on the case, from 1.1 to about 2.5 times more expensive than E-FEM. For multiple cracks, the computational cost of E-FEM keeps constant, whereas the cost associated to X-FEM increases linearly with the number of modelled cracks. Fil: Oliver, J.. Universidad Politecnica de Catalunya; España Fil: Huespe, Alfredo Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina. Universidad Politecnica de Catalunya; España Fil: Sánchez, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Objective To measure the efficacy of valacyclovir suppression in late pregnancy to reduce the incidence of recurrent genital herpes in labor and subsequent cesarean delivery. Methods A total of 350 pregnant women with a history of genital herpes were assigned randomly to oral valacyclovir 500 mg twice a day or an identical placebo from 36 weeks of gestation until delivery. In labor, vulvovaginal herpes simplex virus (HSV) culture and polymerase chain reaction (PCR) specimens were collected. Vaginal delivery was permitted if no clinical recurrence or prodromal symptoms were present. Neonatal HSV cultures and laboratory tests were obtained, and infants were followed up for 1 month after delivery. Data were analyzed using chi2 and Student t tests. Results One hundred seventy women treated with valacyclovir and 168 women treated with placebo were evaluated. Eighty-two percent of the women had recurrent genital herpes; 12% had first episode, nonprimary genital herpes; and 6% had first episode, primary genital herpes. At delivery, 28 women (8%) had recurrent genital herpes requiring cesarean delivery: 4% in the valacyclovir group and 13% in the placebo group (P = .009). Herpes simplex virus was detected by culture in 2% of the valacyclovir group and 9% [corrected] of the placebo group (P =.02). No infants were diagnosed with neonatal HSV, and there were no significant differences in neonatal complications. There were no significant differences in maternal or obstetric complications in either group. Conclusion Valacyclovir suppression after 36 weeks of gestation significantly reduces HSV shedding and recurrent genital herpes requiring cesarean delivery. Level of evidence I.

A stabilized mixed finite element with elemental embedded strong discontinuities for shear band modeling is presented. The discrete constitutive model, representing the cohesive forces acting across the shear band, is derived from a rate-independent J2 plastic continuum material model with strain softening, by using a projection-type procedure determined by the Continuum-Strong Discontinuity Approach. The numerical examples emphasize the increase of the numerical solution accuracy obtained with the present strategy as compared with alternative procedures using linear triangles.

Foetal syphilis is the malady that most medical men think of when reference is made to foetal disease. It has been studied in all its aspects and at very considerable length by a multitude of careful observers. It has been taken as the type of antenatal maladies, as the typical disease of the foetus; it may almost be said that, to some investigators, foetal pathology and foetal syphilis have been synonymous terms. 1

Objective University of Alabama at Birmingham, Birmingham,AL1, University of Mississippi Medical Center, Jackson, MS2 Carolinas Medical Center, Charlotte, NC3, Nationwide Children’s Hospital, Columbus, OH4, Children’s Hospital of Pittsburgh, Pittsburgh, PA5, Cincinnati Children’s Medical Center, Cincinnati, OH6, Saint Peters University Hospital, New Brunswick, NJ7, University of Texas Southwestern Medical School, Dallas, TX8

To evaluate the safety and immunogenicity of palivizumab, 55 children who received palivizumab in the IMpact-RSV trial received 5 monthly doses of 15 mg/kg palivizumab (Synagis) during the subsequent year. The single child with an antipalivizumab titer of >1/40 had no associated serious adverse events and had expected serum palivizumab trough concentrations. Second year palivizumab prophylaxis was safe and well-tolerated.

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. It is associated with an increase in mortality, morbidity, and prolonged length of hospital stay. Thus, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a "real" blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics. As a result, antibiotic use is double the rate of "proven" sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose of this article is to describe simple changes in process, which when implemented, can reduce nosocomial infection rates in neonates and improve outcomes.

Objective The study sought to determine the relationship between cytomegalovirus (CMV) viremia during early infancy and clinical and laboratory outcome events, particularly hearing loss in infants with symptomatic congenital CMV infection involving the central nervous system (CNS). Study design A total of 147 infant patients were enrolled prospectively in 2 clinical trials evaluating ganciclovir for the treatment of symptomatic congenital CMV infection involving the CNS. Aliquots of serum collected at enrollment in either of the 2 trials were available from 50 of the infants, and the degree of viremia was determined by real-time quantitative polymerase chain reaction. Results Of the 50 infants from whom serum samples were available, 37 had detectable CMV DNA in the serum sample collected at enrollment and were classified as viremic. Viremic infants were more likely to have (1) hearing loss both at enrollment (P = .045) and at the 6-month follow-up testing (P = .035) and (2) other indicators of active CMV disease, including elevated levels of alanine aminotransferase, petechial rash, and organomegaly. Conclusion In children with symptomatic congenital CMV infection involving the CNS, viremia during early infancy is associated with hearing loss and systemic CMV disease.

A positive blood culture with a clinically recognized pathogen remains the gold standard for the diagnosis of neonatal sepsis. Debate continues as to whether multiple blood cultures should be performed. Certainly with bacterial organisms that are frequent blood culture contaminants, such as coagulase-negative staphylococci (CoNS), the diagnosis of sepsis is best confirmed by the finding of two or more positive cultures from multiple sites or body fluids that are normally sterile. The isolation of CoNS from only one blood culture when only one is obtained is problematic and of uncertain significance. Since many of these positive cultures represent contamination with skin microflora, the practice of obtaining only one blood culture often leads to prolonged and unnecessary antibiotic therapy. In our neonatal intensive care unit (NICU) at Parkland Memorial Hospital (PMH) in Dallas, Texas, we routinely obtain two blood cultures from all infants who are evaluated for possible sepsis.

Enterovirus (EV) meningitis is common in infants and may have neurologic complications. Treatment of older children and adults with pleconaril has been associated with reduced severity and duration of symptoms. This study evaluated the pharmacokinetics, safety and efficacy of pleconaril in infants with EV meningitis.Infantsor =12 months old with suspected EV meningitis were randomized 2:1 to receive pleconaril, 5 mg/kg/dose orally three times a day or placebo for 7 days. Evaluations included pharmacokinetic determinations, safety laboratory testing, serial culture and PCR assays and clinical evaluations.Of 21 evaluable subjects 20 were confirmed with EV infection (12 pleconaril, 8 placebo). Among pleconaril-treated subjects 26 of 29 peak and trough pleconaril levels exceeded the 90% inhibitory concentration for EVs. A median 3.5-fold drug accumulation occurred between Days 2 and 7. Pleconaril was well-tolerated, although twice as many adverse events occurred per subject in the pleconaril group. Serial cultures from the oropharynx, rectum and serum had low yield (or =50%) and positivity generally persisted for4 days in both groups. Serial PCR assays of culture-negative oropharyngeal and rectal specimens had high positivity rates (generallyor =50%) persisting through Day 14. No significant differences in duration of positivity by culture or PCR, hospitalization or symptoms were detected between groups.The dose of pleconaril studied provided sufficient plasma levels and was well-tolerated; however, drug accumulation was evident. The low yields of serial viral cultures, relatively short and benign clinical courses and the small number of subjects enrolled precluded demonstration of efficacy. If this medication is to be prescribed in infants, surveillance for toxicity related to drug accumulation will be necessary.

Objective. In January 1995, a combined maternal and neonatal protocol for prevention of early-onset group B streptococcal (GBS) infection was implemented that consisted of a risk factor-based approach for maternal intrapartum chemoprophylaxis using ampicillin combined with a single intramuscular dose of penicillin given to all newborns within 1 hour of delivery. The objective of this study was to review the cases of early-onset GBS infections that occurred from 1995 to 1999 to identify factors associated with their continued occurrence despite implementation of a GBS chemoprophylaxis protocol.Methods. Infants ≤72 hours of age with early-onset GBS infection born at Parkland Memorial Hospital in Dallas from January 1995 to December 1999 were identified through a prospective laboratory-based surveillance system. Maternal and infant medical records were reviewed for clinical and demographic data.Results. There were 32 cases (0.47/1000 live births) of early-onset GBS infection for the 5-year period. This represented a 76% reduction compared with the rate from 1986 to 1994 (1.95/1000), when there was no protocol for GBS chemoprophylaxis. Thirteen cases (41%) did not have any identifiable maternal risk factor. Of the 19 cases (59%) with risk factors, maternal intrapartum fever was the most frequent (15 [79%]), followed by prematurity (6 [32%]) and prolonged rupture of membranes (6 [32%]). Among the 19 mothers with risk factors, 15 (79%) mothers received intrapartum chemoprophylaxis, and 12 (80%) of the 15 mothers had intrapartum fever. Only 33% of mothers with risk factors received ≥2 doses of intrapartum chemoprophylaxis, and among those with intrapartum fever, 25% received ≥2 doses. None of the 32 infants with early-onset GBS infection received the combination of intrapartum ampicillin and postnatal penicillin.Conclusions. A combined obstetric and neonatal chemoprophylaxis protocol significantly reduced early-onset GBS infection. Maternal intrapartum fever was the most frequent risk factor associated with failure of chemoprophylaxis.

Antimicrobial therapy can ameliorate infection and prevent long-term morbidity caused by several pathogens that infect the fetus and neonate. Ultimately, however, preventive strategies need to be developed and incorporated into routine preconceptional care. The future of prevention lies in immunizations, and if past and current successes with smallpox, polio, rubella, and measles vaccination programs are any indication, the future is bright for the developing fetus.