Creating and studying ion acoustic waves in ultracold neutral plasmas

We excite ion acoustic waves in ultracold neutral plasmas by imprinting density modulations during plasma creation. Laser-induced fluorescence is used to observe the density and velocity perturbations created by the waves. The effect of expansion of the plasma on the evolution of the wave amplitude is described by treating the wave action as an adiabatic invariant. After accounting for this effect, we determine that the waves are weakly damped, but the damping is significantly faster than expected for Landau damping

Towards the “Baby Connectome”: Mapping the Structural Connectivity of the Newborn Brain

Defining the structural and functional connectivity of the human brain (the human “connectome”) is a basic challenge in neuroscience. Recently, techniques for noninvasively characterizing structural connectivity networks in the adult brain have been developed using diffusion and high-resolution anatomic MRI. The purpose of this study was to establish a framework for assessing structural connectivity in the newborn brain at any stage of development and to show how network properties can be derived in a clinical cohort of six-month old infants sustaining perinatal hypoxic ischemic encephalopathy (HIE). Two different anatomically unconstrained parcellation schemes were proposed and the resulting network metrics were correlated with neurological outcome at 6 months. Elimination and correction of unreliable data, automated parcellation of the cortical surface, and assembling the large-scale baby connectome allowed an unbiased study of the network properties of the newborn brain using graph theoretic analysis. In the application to infants with HIE, a trend to declining brain network integration and segregation was observed with increasing neuromotor deficit scores

3D global and regional patterns of human fetal subplate growth determined in utero

The waiting period of subplate evolution is a critical phase for the proper formation of neural connections in the brain. During this time, which corresponds to 15 to 24 postconceptual weeks (PCW) in the human fetus, thalamocortical and cortico-cortical afferents wait in and are in part guided by molecules embedded in the extracellular matrix of the subplate. Recent advances in fetal MRI techniques now allow us to study the developing brain anatomy in 3D from in utero imaging. We describe a reliable segmentation protocol to delineate the boundaries of the subplate from T2-W MRI. The reliability of the protocol was evaluated in terms of intra-rater reproducibility on a subset of the subjects. We also present the first 3D quantitative analyses of temporal changes in subplate volume, thickness, and contrast from 18 to 24 PCW. Our analysis shows that firstly, global subplate volume increases in proportion with the supratentorial volume; the subplate remained approximately one-third of supratentorial volume. Secondly, we found both global and regional growth in subplate thickness and a linear increase in the median and maximum subplate thickness through the waiting period. Furthermore, we found that posterior regions—specifically the occipital pole, ventral occipito-temporal region, and planum temporale—of the developing brain underwent the most statistically significant increases in subplate thickness. During this period, the thickest region was the developing somatosensory/motor cortex. The subplate growth patterns reported here may be used as a baseline for comparison to abnormal fetal brain development

White matter injury in term neonates with congenital heart diseases: Topology & comparison with preterm newborns

Background: Neonates with congenital heart disease (CHD) are at high risk of punctate white matter injury (WMI) and impaired brain development. We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age (GA) is associated with larger WMI volume. Objective: (1) To quantitatively assess the volume and location of WMI in CHD neonates across three centres. (2) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping. Methods: In 216 term born CHD neonates from three prospective cohorts (mean birth GA: 39 weeks), WMI was identified in 86 neonates (UBC: 29; UCSF: 43; UCZ: 14) on pre- and/or post-operative T1 weighted MRI. WMI was manually segmented and volumes were calculated. A standard brain template was generated. Probabilistic WMI maps (total, pre- and post-operative) were developed in this common space. Using these maps, WMI in the term CHD neonates was compared with that in preterm neonates: 58 at early-in-life (mean postmenstrual age at scan 32.2 weeks); 41 at term-equivalent age (mean postmenstrual age at scan 40.1 weeks). Results: The total WMI volumes of CHD neonates across centres did not differ (p = 0.068): UBC (median = 84.6 mm 3 , IQR = 26–174.7 mm 3 ); UCSF (median = 104 mm 3 , IQR = 44–243 mm 3 ); UCZ (median = 121 mm 3 , IQR = 68–200.8 mm 3 ). The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions. Predominance of anterior lesions was apparent on the post-operative WMI map relative to the pre-operative map. Lower GA at birth predicted an increasing volume of WMI across the full cohort (41.1 mm 3 increase of WMI per week decrease in gestational age; 95% CI 11.5–70.8; p = 0.007), when accounting for centre and heart lesion. While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms. Conclusions: WMI in term neonates with CHD occurs in a characteristic topology. The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre-oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates

Renal and neurological side effects of colistin in critically ill patients

Colistin is a complex polypeptide antibiotic composed mainly of colistin A and B. It was abandoned from clinical use in the 1970s because of significant renal and, to a lesser extent, neurological toxicity. Actually, colistin is increasingly put forward as salvage or even first-line treatment for severe multidrug-resistant, Gram-negative bacterial infections, particularly in the intensive care setting. We reviewed the most recent literature on colistin treatment, focusing on efficacy and toxicity issues. The method used for literature search was based on a PubMed retrieval using very precise criteria

Diffusion tensor imaging of the cortical plate and subplate in very-low-birth-weight infants

Background: Many intervention studies in preterm infants aim to improve neurodevelopmental outcome, but short-term proxy outcome measurements are lacking. Cortical plate and subplate development could be such a marker. Objective: Our aim was to provide normal DTI reference values for the cortical plate and subplate of preterm infants. Materials and methods: As part of an ongoing study we analysed diffusion tensor imaging (DTI) images of 19 preterm infants without evidence of injury on conventional MRI, with normal outcome (Bayley-II assessed at age 2), and scanned in the first 4 days of life. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in the frontal and temporal subplate and cortical plate were measured in single and multiple voxel regions of interest (ROI) placed on predefined regions. Results: Using single-voxel ROIs, statistically significant inverse correlation was found between gestational age (GA) and FA of the frontal (r = -0.5938, P = 0.0058) and temporal (r = -0.4912, P = 0.0327) cortical plate. ADC values had a significant positive correlation with GA in the frontal (r = 0.5427, P = 0.0164) and temporal (r = 0.5540, P = 0.0138) subplate. Conclusion: Diffusion tensor imaging allows in vivo exploration of the evolving cortical plate and subplate. We provide FA and ADC values of the subplate and cortical plate in very-low-birth-weight (VLBW) infants with normal developmental outcome that can be used as reference values

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children’s hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P = 0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P = 0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P = 0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087.

Adherence to recommendations by infectious disease consultants and its influence on outcomes of intravenous antibiotic-treated hospitalized patients

BACKGROUND: Consultation to infectious diseases specialists (ID), although not always performed by treating physicians, is part of hospital's daily practice. This study analyses adherence by treating physicians to written ID recommendations (inserted in clinical records) and its effect on outcome in hospitalized antibiotic-treated patients in a tertiary hospital in Spain. METHODS: A prospective, randomized, one-year study was performed. Patients receiving intravenous antimicrobial therapy prescribed by treating physicians for 3 days were identified and randomised to intervention (insertion of written ID recommendations in clinical records) or non-intervention. Appropriateness of empirical treatments (by treating physicians) was classified as adequate, inadequate or unnecessary. In the intervention group, adherence to recommendations was classified as complete, partial or non-adherence. RESULTS: A total of 1173 patients were included, 602 in the non-intervention and 571 in the intervention group [199 (34.9%) showing complete adherence, 141 (24.7%) partial adherence and 231 (40.5%) non-adherence to recommendations]. In the multivariate analysis for adherence (R2 Cox=0.065, p=0.009), non-adherence was associated with prolonged antibiotic prophylaxis (p=0.004; OR=0.37, 95%CI=0.19-0.72). In the multivariate analysis for clinical failure (R2 Cox=0.126, p<0.001), Charlson index (p<0.001; OR=1.19, 95%CI=1.10-1.28), malnutrition (p=0.006; OR=2.00, 95%CI=1.22-3.26), nosocomial infection (p<0.001; OR=4.12, 95%CI=2.27-7.48) and length of hospitalization (p<0.001; OR=1.01, 95%CI=1.01-1.02) were positively associated with failure, while complete adherence (p=0.001; OR=0.35, 95%CI=0.19-0.64) and adequate initial treatment (p=0.010; OR=0.39, 95%CI=0.19-0.80) were negatively associated. CONCLUSIONS: Adherence to ID recommendations by treating physicians was associated with favorable outcome, in turn associated with shortened length of hospitalization. This may have important health-economic benefits and stimulates further investigation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN83234896. http://www.controlled-trials.com/isrctn/sample_documentation.asp

The Meningococcal Vaccine Candidate Neisserial Surface Protein A (NspA) Binds to Factor H and Enhances Meningococcal Resistance to Complement

Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH) to fH-binding protein (fHbp) is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a ∼17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA), a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep) I chain of lipooligosaccharide (LOS), or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6–7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components