Maternal parechovirus A (PeV-A) shedding, serostatus, and the risk of central nervous system PeV-A infections in infants.

BACKGROUND: Parechovirus A (PeV-A) has emerged as a leading cause of infant central nervous system (CNS) infections. Risk factors associated with infant acquisition of PeV-A are not well understood. METHODS: We conducted prospective PeV-A/enterovirus (EV) CNS infection surveillance, enrolling 461 hospitalized infants <90 days old who underwent sepsis evaluations and lumbar puncture during 2011-2012. Infants were grouped by RT-PCR detection of PeV-A, EV, or neither virus (Neg) in CSF. We collected demographic/clinical data and tested specimens from all infants. For 427 mothers, we collected demographic/clinical data and evaluated PeV-A3 and EV shedding, and PeV-A3 neutralizing antibody for 147 mothers. RESULTS: PeV-A was detected in 40 infants (8.7%), 4 in 2011 and 36 in 2012. EV was detected in 35 infants (7.6%), 16 in 2011, and 19 in 2012. PeV-A infected infants presented with irritability, abdominal discomfort, fever, and tachycardia, plus both lymphopenia and absence of CSF pleocytosis which help differentiate PeV-A from EV CNS infection. PeV-A was detected in 9/427 maternal throat swabs; eight of their infants also had PeV-A CNS infection. Infants whose mothers had PeV-A3-positive throat swabs were more likely to be PeV-A3-positive than infants whose mothers had negative throat swabs (relative risk [RR], 13.4 [95% CI, 8.6 - 20.7]). Maternal PeV-A3 seropositivity decreased with increasing maternal age. Mothers of PeV-A-positive infants had lower median PeV-A3 neutralizing titers and were more likely seronegative. CONCLUSIONS: Maternal viral shedding, serostatus and neutralization titers appear to be important factors in infant PeV-A3 CNS infections.

Clinical Practice Guideline for the Management of Infantile Hemangiomas.

Infantile hemangiomas (IHs) occur in as many as 5% of infants, making them the most common benign tumor of infancy. Most IHs are small, innocuous, self-resolving, and require no treatment. However, because of their size or location, a significant minority of IHs are potentially problematic. These include IHs that may cause permanent scarring and disfigurement (eg, facial IHs), hepatic or airway IHs, and IHs with the potential for functional impairment (eg, periorbital IHs), ulceration (that may cause pain or scarring), and associated underlying abnormalities (eg, intracranial and aortic arch vascular abnormalities accompanying a large facial IH). This clinical practice guideline for the management of IHs emphasizes several key concepts. It defines those IHs that are potentially higher risk and should prompt concern, and emphasizes increased vigilance, consideration of active treatment and, when appropriate, specialty consultation. It discusses the specific growth characteristics of IHs, that is, that the most rapid and significant growth occurs between 1 and 3 months of age and that growth is completed by 5 months of age in most cases. Because many IHs leave behind permanent skin changes, there is a window of opportunity to treat higher-risk IHs and optimize outcomes. Early intervention and/or referral (ideally by 1 month of age) is recommended for infants who have potentially problematic IHs. When systemic treatment is indicated, propranolol is the drug of choice at a dose of 2 to 3 mg/kg per day. Treatment typically is continued for at least 6 months and often is maintained until 12 months of age (occasionally longer). Topical timolol may be used to treat select small, thin, superficial IHs. Surgery and/or laser treatment are most useful for the treatment of residual skin changes after involution and, less commonly, may be considered earlier to treat some IHs.

Clinical Impact of an Antimicrobial Stewardship Program on Pediatric Hospitalist Practice, a 5-Year Retrospective Analysis.

BACKGROUND AND OBJECTIVES: Hospitalists increasingly serve as the primary physicians for children hospitalized with infections. Consequently, hospitalists frequently interact with institutional antimicrobial stewardship programs (ASPs). Understanding how these services interact can inform ongoing practice improvement efforts. The objectives of this study were to identify factors associated with ASP recommendations among hospitalist-managed children, and to determine the association of ASP interventions with clinical outcomes for hospitalist-managed patients. METHODS: We retrospectively analyzed ASP reviews of hospitalist patients from a children's hospital from March 2008 to June 2013. Clinical factors associated with an ASP recommendation were determined. Length of stay and 30-day readmission were compared between cases of agreement and disagreement with ASP recommendations. RESULTS: The ASP reviewed 2163 hospitalist patients, resulting in 350 recommendations (16.2% of reviews). Hospitalists agreed with ASP recommendations in 86.9% of cases. The odds of an ASP recommendation decreased during the study period. Ceftriaxone was the most common antibiotic associated with a recommendation (154/350, 44.0%); community-acquired pneumonia was the most common diagnosis (105/350, 30.0%). Antibiotic discontinuation was the most often recommendation; hospitalists most often disagreed with consulting infectious diseases. Disagreement with ASP recommendations was associated with a decreased length of stay of 15.4 (95% confidence interval -33.2 to 1.1) hours but not 30-day readmission prevalence. CONCLUSIONS: Pediatric hospitalists and ASPs can form an effective collaboration that improves antibiotic use while providing safe care. Better characterization of the areas of disagreement between hospitalists and ASPs is needed. Future studies are needed to identify ASP strategies that will be beneficial in other hospitalist settings.

Variability of intensive care management for children with bronchiolitis.

OBJECTIVE: To determine the extent of variability in testing and treatment of children with bronchiolitis requiring intensive care. METHODS: This prospective, multicenter observational study included 16 academic children's hospitals across the United States during the 2007 to 2010 fall and winter seasons. The study included children<2 years old hospitalized with bronchiolitis who required admission to the ICU and/or continuous positive airway pressure (CPAP) within 24 hours of admission. Among the 2207 enrolled patients with bronchiolitis, 342 children met inclusion criteria. Clinical data and nasopharyngeal aspirates were collected. RESULTS: Respiratory distress severity scores and intraclass correlation coefficients were calculated. The study patients' median age was 2.6 months, and 59% were male. Across the 16 sites, the median respiratory distress severity score was 5.1 (interquartile range: 4.5-5.4; P<.001). The median value of the percentages for all sites using CPAP was 15% (range: 3%-100%), intubation was 26% (range: 0%-100%), and high-flow nasal cannula (HFNC) was 24% (range: 0%-94%). Adjusting for site-specific random effects (as well as children's demographic characteristics and severity of bronchiolitis), the intraclass correlation coefficient for CPAP and/or intubation was 21% (95% confidence interval: 8-44); for HFNC, it was 44.7% (95% confidence interval: 24-67). CONCLUSIONS: In this multicenter study of children requiring intensive care for bronchiolitis, we identified substantial institutional variability in testing and treatment, including use of CPAP, intubation, and HFNC. These differences were not explained by between-site differences in patient characteristics, including severity of illness. Further research is needed to identify best practices for intensive care interventions for this major cause of pediatric hospitalization.

Autonomic molecular transport by polymer films containing programmed chemical potential gradients.

Materials which induce molecular motion without external input offer unique opportunities for spatial manipulation of molecules. Here, we present the use of polyacrylamide hydrogel films containing built-in chemical gradients (enthalpic gradients) to direct molecular transport. Using a cationic tertiary amine gradient, anionic molecules were directionally transported up to several millimeters. A 40-fold concentration of anionic molecules dosed in aerosol form on a substrate to a small region at the center of a radially symmetric cationic gradient was observed. The separation of mixtures of charged dye molecules was demonstrated using a boronic acid-to-cationic gradient where one molecule was attracted to the boronic acid end of the gradient, and the other to the cationic end of the gradient. Theoretical and computational analysis provides a quantitative description of such anisotropic molecular transport, and reveals that the gradient-imposed drift velocity is in the range of hundreds of nanometers per second, comparable to the transport velocities of biomolecular motors. This general concept of enthalpy gradient-directed molecular transport should enable the autonomous processing of a diversity of chemical species.

Hospital course and discharge criteria for children hospitalized with bronchiolitis.

BACKGROUND: For children hospitalized with bronchiolitis, there is uncertainty about the expected inpatient clinical course and when children are safe for discharge. OBJECTIVES: Examine the time to clinical improvement, risk of clinical worsening after improvement, and develop discharge criteria. DESIGN: Prospective multiyear cohort study. SETTING: Sixteen US hospitals. PARTICIPANTS: Consecutive hospitalized children age <2 years with bronchiolitis. MEASUREMENT: We defined clinical improvement using: (1) retraction severity, (2) respiratory rate, (3) room air oxygen saturation, and (4) hydration status. After meeting improvement criteria, children were considered clinically worse based on the inverse of ≥1 of these criteria or need for intensive care. RESULTS: Among 1916 children, the median number of days from onset of difficulty breathing until clinical improvement was 4 (interquartile range, 3-7.5 days). Of the total, 1702 (88%) met clinical improvement criteria, with 4% worsening (3% required intensive care). Children who worsened were age <2 months (adjusted odds ratio [AOR]: 3.51; 95% confidence interval [CI]: 2.07-5.94), gestational age <37 weeks (AOR: 1.94; 95% CI: 1.13-3.32), and presented with severe retractions (AOR: 5.55; 95% CI: 2.12-14.50), inadequate oral intake (AOR: 2.54; 95% CI: 1.39-4.62), or apnea (AOR: 2.87; 95% CI: 1.45-5.68). Readmissions were similar for children who did and did not worsen. CONCLUSIONS: Although children hospitalized with bronchiolitis had wide-ranging recovery times, only 4% worsened after initial improvement. Children who worsened were more likely to be younger, premature infants presenting in more severe distress. For children hospitalized with bronchiolitis, these data may help establish more evidence-based discharge criteria, reduce practice variability, and safely shorten hospital length-of-stay.

Risk factors for requiring intensive care among children admitted to ward with bronchiolitis.

OBJECTIVE: To examine risk factors for transfer of bronchiolitis patients from the ward to the intensive care unit (ICU) and/or initiation of critical care interventions. METHODS: We performed a 16-center, prospective cohort study of hospitalized children age <2 years with bronchiolitis. During the winters of 2007 to 2010, researchers collected clinical data and nasopharyngeal aspirates from study participants. The primary outcome was late intensive care use, defined as a transfer to the ICU and/or use of mechanical ventilation (regardless of location) after the child's first inpatient day. RESULTS: Among 2104 children hospitalized with bronchiolitis, 1762 (84%) were identified as initial ward patients, comprising the analysis cohort. The median age was 4 months (interquartile range, 2-9 months), and 1048 (59%) were boys. The most frequently detected pathogens were respiratory syncytial virus (72%) and rhinovirus (25%). After the first inpatient day, 47 (3%; 95% confidence interval, 2-4) were subsequently transferred to the ICU or required mechanical ventilation. In the multivariable logistic regression model predicting subsequent transfer to the ICU or mechanical ventilation use, the significant predictors were birth weight <5 pounds (odds ratio, 2.28; 95% confidence interval, 1.30-4.02; P = .004) and respiratory rate high of ≥ 70 breaths/min on the first inpatient day (odds ratio, 4.64; 95% confidence interval, 2.86-7.53; P < .001). CONCLUSIONS: In this multicenter study of children hospitalized with bronchiolitis, low birth weight and tachypnea were significantly associated with subsequent transfer to the ICU and/or use of mechanical ventilation.

Change to a standardized airway clearance protocol for children with bronchiolitis leads to improved care.

Nurses at a pediatric hospital identified the liberal utilization of deep nasopharyngeal (NP) suction as the primary airway clearance modality in young children with bronchiolitis. This invasive practice lacked supporting evidence and a standardized approach. Nurses created an interdisciplinary team to develop a less invasive airway clearance protocol. Data from 2years, both pre and post protocol implementation, were analyzed. An 11% decrease in deep NP suctioning resulted in improved or unchanged balancing measures and perceptions of quality of care.

Diagnosis and acute management of patients with concussion at children's hospitals.

OBJECTIVES: To describe the number of hospital admissions for concussion at paediatric hospitals in the USA. To describe the use of imaging and medications for acute concussion paediatric patients. DESIGN: Cross-sectional study. SETTING: Children's hospitals participating in the Pediatric Health Information System in the USA during a 10-year period. PATIENTS: All emergency department (ED) visits and inpatient admissions with the primary diagnosis of concussion, defined as International Classification of Diseases, Ninth Revision, Clinical Modification codes for: (1) concussion, (2) postconcussion syndrome or (3) skull fracture without mention of intracranial injury with concussion. MAIN OUTCOME MEASURES: The proportion of concussion patients who were hospitalised, underwent imaging or received medication, and the adjusted costs of visits for concussion. RESULTS: The number of ED visits for concussion increased between 2001 and 2010 (2126 (0.36% of all ED visits) vs 4967 (0.62% of all ED visits); p<0.001), while the number of admissions remained stable. Of ED visits for concussion, 59.9% received CT and 47.7% received medications or intravenous fluids. Non-narcotic analgesics were the most common medication administered. Adjusted costs of patient visits were significantly higher when imaging was obtained (US$695, IQR US$472-$1009, vs US$191, IQR US$114-$287). An ED visit with CT, however, cost less than a hospitalisation without CT (US$1907, IQR US$1292-$3770). CONCLUSIONS: Although the number of ED patients diagnosed with concussion has increased, the number admitted has remained stable. Concussion patients at paediatric hospitals in the USA commonly undergo CT imaging and receive medication.

Chemical gradients on graphene to drive droplet motion.

This work demonstrates the production of a well-controlled, chemical gradient on the surface of graphene. By inducing a gradient of oxygen functional groups, drops of water and dimethyl-methylphosphonate (a nerve agent simulant) are "pulled" in the direction of increasing oxygen content, while fluorine gradients "push" the droplet motion in the direction of decreasing fluorine content. The direction of motion is broadly attributed to increasing/decreasing hydrophilicity, which is correlated to high/low adhesion and binding energy. Such tunability in surface chemistry provides additional capabilities in device design for applications ranging from microfluidics to chemical sensing.

Decreasing unnecessary utilization in acute bronchiolitis care: results from the value in inpatient pediatrics network.

BACKGROUND: Acute viral bronchiolitis is the most common diagnosis resulting in hospital admission in pediatrics. Utilization of non-evidence-based therapies and testing remains common despite a large volume of evidence to guide quality improvement efforts. OBJECTIVE: Our objective was to reduce utilization of unnecessary therapies in the inpatient care of bronchiolitis across a diverse network of clinical sites. METHODS: We formed a voluntary quality improvement collaborative of pediatric hospitalists for the purpose of benchmarking the use of bronchodilators, steroids, chest radiography, chest physiotherapy, and viral testing in bronchiolitis using hospital administrative data. We shared resources within the network, including protocols, scores, order sets, and key bibliographies, and established group norms for decreasing utilization. RESULTS: Aggregate data on 11,568 hospitalizations for bronchiolitis from 17 centers was analyzed for this report. The network was organized in 2008. By 2010, we saw a 46% reduction in overall volume of bronchodilators used, a 3.4 dose per patient absolute decrease in utilization (95% confidence interval [CI] 1.4-5.8). Overall exposure to any dose of bronchodilator decreased by 12 percentage points as well (95% CI 5%-25%). There was also a statistically significant decline in chest physiotherapy usage, but not for steroids, chest radiography, or viral testing. CONCLUSIONS: Benchmarking within a voluntary pediatric hospitalist collaborative facilitated decreased utilization of bronchodilators and chest physiotherapy in bronchiolitis.

Effect of film thickness on the columnar packing structures of discotic supramolecules in thin films.

The effects of film thickness on the columnar packing structure of discotic supramolecules in a thin supported film have been investigated by grazing-incidence small-angle X-ray scattering technique using magnetically aligned cobalt octa(n-decylthio)porphyrazine (CoS10) films on octadecyltrichlorosilane (OTS)-functionalized substrates as model systems. Magnetically aligned CoS10 films with a range of film thicknesses (49-845 nm) form uniaxially oriented 'edge-on' columnar superstructures with their columnar directors perpendicular to the applied magnetic field. However, the orientational ordering of the columnar packing in the plane perpendicular to the applied magnetic field is strongly dependent on the film thickness. While being damped by the elasticity of the side chains of CoS10, the strong interfacial interaction at the film-substrate interface propagates up to 50-100 nm from the substrate, maintaining the orientation of columnar packing in the plane perpendicular to the applied magnetic field. When the distance from the film-substrate interface becomes larger than about 100 nm, symmetric tilting of columnar layer orientation, which saturates at 11.5 degrees , occurs due to longitudinal edge dislocations induced by accumulated elastic deformation.

Fabrication of 2D ordered films of tobacco mosaic virus (TMV): processing morphology correlations for convective assembly.

Biological colloids, and in particular viruses, have demonstrated substantial potential as scaffolds for nanoparticle arrays. However, the large-area, low-cost, and rapid assembly of viruses, such as by traditional colloidal processing techniques, is not well-established. Systematic exploration of processing space (virus concentration, assembly speed, and substrate surface energy) for the convective assembly method enables the fabrication of films of rod-shaped viruses (tobacco mosaic virus, TMV) with a high degree of long-range order. Monolayer assemblies several centimeters in length are comprised of TMV aligned parallel to the direction of assembly. Increasing TMV concentration and reducing assembly speed resulted in well-ordered viral layering ( N = 2 to N = 12); however, the top virus layer exhibits varying degrees of in-plane disorder.

perpendicular organization of macromolecules: synthesis and alignment studies of a soluble poly(iptycene).

We describe herein a polymeric material that prefers to align perpendicular to a stretch-aligned polymer host in the solid state. Poly(iptycene) poly-1 was synthesized from monomer 1 under hyperbaric techniques via a Diels-Alder polymerization. Polarized excitation spectra of the anthracene end groups in this material in a stretch-aligned, solution-cast poly(vinyl chloride) (PVC) film showed that the poly(iptycene) prefers to align normal (counter aspect ratio) to the stretching direction of the PVC. This is explained by a "threading" mechanism, whereby the PVC intercalates through the internal free volume presented by poly-1, similar to effects observed in small molecule iptycenes under similar conditions.

Cations M2(O2CtBu)4+, where M = Mo and W, and MoW(O2CtBu)4+. Theoretical, spectroscopic, and structural investigations.

With the aid of density function theory, the molecular and electronic structures of the molecules Mo2(O2CMe)4, MoW(O2CMe)4, and W2(O2CMe)4 and their single-electron oxidized radical cations have been determined; this includes calculated observables such as v(MM) and the delta --> delta* electronic transition energies. The calculated properties are compared with those for the corresponding pivalates, M2(O2CtBu)4 (M = Mo or W) and MoW(O2CtBu)4 and their radical cations prepared in situ by oxidation with Cp2FePF6. The EPR spectra of the radical cations are also reported. The EPR spectrum of the MoW(O2CtBu)4+ cation reveals that the unpaired electron is in a polarized MM delta orbital having 70% Mo and 30% W character. The MM stretching frequencies show good correlation with the MM bond lengths obtained from single-crystal X-ray diffraction studies of MoW(O2CtBu)4, W2(O2CtBu)4, and W2(O2CtBu)4+PF6- compounds, along with previously reported structures. These data provide benchmark parameters for valence trapped dicarboxylate bridged radical cations of the type [(tBuCO2)3M2]2(micro-O2C-X-CO2)+ (X = conjugated spacer).

9,10-Anthracene dicarboxylate bridged complexes with M2 quadruply bonded dimetal units: [[M2(O2CtBu)3]2(mu-9,10-An(CO2)2)], where M = Mo or W.

From the reactions between [M2(O2CtBu)4] and 9,10-anthracenedicarboxylic acid in toluene, the dicarboxylate bridged complexes [[M2(O2CtBu)3]2(mu-9,10An(CO2)2)], have been obtained as microcrystalline yellow (M = Mo) and red (M = W) powders. The powders are soluble in THF forming intense red (M = Mo) and green (M = W) solutions. The electronic absorption spectra in 2-MeTHF have been recorded as a function of temperature (2-298 K) and show a small bathochromic shift on cooling. The electronic structures have been investigated by molecular orbital calculations employing density functional theory on the model compounds [(HCO2)3M2]2(mu-9,10-An(CO2)2) where the M4 unit is constrained to lie in a plane. These reveal a minimum energy, gas-phase structure wherein the plane of the anthracene is twisted by ca. 54 degrees with respect to its 9,10-carboxylate units for both Mo and W. The results of these calculations are correlated with the electronic absorption spectral data and the electrochemical measurements (CV and DPV) of the first and second oxidation waves. The EPR spectra of the radical cations formed by single-electron oxidation with [Cp2Fe](+)[PF6]- in a THF-CH2Cl2 solvent mixture show that the complexes are valence trapped at ambient temperature on the EPR timescale. These results are discussed in the light of recent studies of dicarboxylate-linked MM quadruple bonds.

On the electron delocalization in the radical cations formed by oxidation of MM quadruple bonds linked by oxalate and perfluoroterephthalate bridges.

Electron paramagnetic resonance, electronic absorption, and resonance Raman spectroscopy reveal that in the oxalate-bridged compounds, [[(tBuCO2)3M2]2(mu-O2CCO2)]+[PF6]-, the unpaired electron is delocalized over four metal centers (M = Mo or W) as a result of M2 delta to bridge pi conjugation, but in the related cationic perfluoroterephthalate-bridged species, the tungsten complex is delocalized and the molybdenum analogue valence trapped.

Third-order nonlinear optical properties of complexes with MM triple and quadruple bonds (M = Mo, W) at 1064 nm by degenerate four-wave mixing.

Measurements of the third-order nonlinear optical responses of solutions of the metal-metal multiply bonded complexes Mo(2)(OPr(i))(6), W(2)(OBu(t))(6), M(2)(NMe(2))(6), M(2)(O(2)CBu(t))(4), and M(2)Cl(4)(PMe(3))(4) (M = Mo, W), using picosecond degenerate four-wave mixing at 1064 nm, are reported. These complexes display only very small instantaneous electronic polarizations when excited with cross-polarized beams. When the excitation beams are similarly polarized, a significant third-order optical response is detected, which is attributable to the formation of bulk thermal excitation gratings. Time-dependent measurements support this view.