Neural Processing of Repetition and Non-Repetition Grammars in 7- and 9-Month-Old Infants

An essential aspect of infant language development involves the extraction of meaningful information from a continuous stream of auditory input. Studies have identified early abilities to differentiate auditory input along various dimensions, including the presence or absence of structural regularities. In newborn infants, frontal and temporal regions were found to respond differentially to these regularities (Gervain et al., 2008), and in order to examine the development of this abstract rule learning we presented 7- and 9-month-old infants with syllables containing an ABB pattern (e.g., “balolo”) or an ABC pattern (e.g., “baloti”) and measured activity in left and right lateral brain regions using near-infrared spectroscopy (NIRS). While prior newborn work found increases in oxyhemoglobin (oxyHb) activity in response to ABB blocks as compared to ABC blocks in anterior regions, 7- and 9-month-olds showed no differentiation between grammars in oxyHb. However, changes in deoxyhemoglobin (deoxyHb) pointed to a developmental shift, whereby 7-month-olds showed deoxyHb responding significantly different from zero for ABB blocks, but not ABC blocks, and 9-month-olds showed the opposite pattern, with deoxyHb responding significantly different from zero for the ABC blocks but not the ABB blocks. DeoxyHb responses were more pronounced over anterior regions. A grammar by time interaction also illustrated that during the early blocks, deoxyHb was significantly greater to ABC than in later blocks, but there was no change in ABB activation over time. The shift from stronger activation to ABB in newborns (Gervain et al., 2008) and 7-month-olds in the present study to stronger activation to ABC by 9-month-olds here is discussed in terms of changes in stimulus salience and novelty preference over the first year of life. The present discussion also highlights the importance of future work exploring the coupling between oxyHb and deoxyHb activation in infant NIRS studies

Timing of Intervention Affects Brain Electrical Activity in Children Exposed to Severe Psychosocial Neglect

Background: Early psychosocial deprivation has profound effects on brain activity in the young child. Previous reports have shown increased power in slow frequencies of the electroencephalogram (EEG), primarily in the theta band, and decreased power in higher alpha and beta band frequencies in infants and children who have experienced institutional care. Methodology/Principal Findings: We assessed the consequences of removing infants from institutions and placing them into a foster care intervention on brain electrical activity when children were 8 years of age. We found the intervention was successful for increasing high frequency EEG alpha power, with effects being most pronounced for children placed into foster care before 24 months of age. Conclusions/Significance: The dependence on age of placement for the effects observed on high frequency EEG alpha power suggests a sensitive period after which brain activity in the face of severe psychosocial deprivation is less amenable to recover

Determination of Optimal Deployment Strategy For Reboa in Patients With Non-Compressible Hemorrhage Below the Diaphragm

BACKGROUND: Non-compressible truncal hemorrhage (NCTH) is the leading cause of preventable death after trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) achieves temporary hemorrhage control, supporting cardiac and cerebral perfusion prior to definitive hemostasis. Aortic zone selection algorithms vary among institutions. We evaluated the efficacy of an algorithm for REBOA use. METHODS: A multicenter prospective, observational study conducted at six level 1 trauma centers over 12 months. Inclusion criteria were age \u3e15 years with evidence of infradiaphragmatic NCTH needing emergent hemorrhage control within 60 min of ED arrival. An algorithm characterized by the results of focused assessment with sonography in trauma and pelvic X-ray was assessed post hoc for efficacy in a cohort of patients receiving REBOA. RESULTS: Of the 8166 patients screened, 78 patients had a REBOA placed. 21 patients were excluded, leaving 57 patients for analysis. The algorithm ensures REBOA deployment proximal to hemorrhage source to control bleeding in 98.2% of cases and accurately predicts the optimal REBOA zone in 78.9% of cases. If the algorithm was violated, bleeding was optimally controlled in only 43.8% (p=0.01). Three (75.0%) of the patients that received an inappropriate zone 1 REBOA died, two from multiple organ failure (MOF). All three patients that died with an inappropriate zone 3 REBOA died from exsanguination. DISCUSSION: This algorithm ensures proximal hemorrhage control and accurately predicts the primary source of hemorrhage. We propose a new algorithm that will be more inclusive. A zone 3 REBOA should not be performed when a zone 1 is indicated by the algorithm as 100% of these patients exsanguinated. MOF, perhaps from visceral ischemia in patients with an inappropriate zone 1 REBOA, may have been prevented with zone 3 placement or limited zone 1 occlusion time. LEVEL OF EVIDENCE: Level III

Endurance of SN 2005ip after a decade: X-rays, radio, and H-alpha like SN 1988Z require long-lived pre-supernova mass loss

SN2005ip was a TypeIIn event notable for its sustained strong interaction with circumstellar material (CSM), coronal emission lines, and IR excess, interpreted as shock interaction with the very dense and clumpy wind of an extreme red supergiant. We present a series of late-time spectra of SN2005ip and a first radio detection of this SN, plus late-time X-rays, all of which indicate that its CSM interaction is still strong a decade post-explosion. We also present and discuss new spectra of geriatric SNe with continued CSM interaction: SN1988Z, SN1993J, and SN1998S. From 3-10 yr post-explosion, SN2005ip's H-alpha luminosity and other observed characteristics were nearly identical to those of the radio-luminous SN1988Z, and much more luminous than SNe1993J and 1998S. At 10 yr after explosion, SN2005ip showed a drop in H$\alpha$ luminosity, followed by a quick resurgence over several months. We interpret this variability as ejecta crashing into a dense shell located at around 0.05 pc from the star, which may be the same shell that caused the IR echo at earlier epochs. The extreme H-alpha luminosities in SN2005ip and SN1988Z are still dominated by the forward shock at 10 yr post-explosion, whereas SN1993J and SN1998S are dominated by the reverse shock at a similar age. Continuous strong CSM interaction in SNe~2005ip and 1988Z is indicative of enhanced mass loss for about 1e3 yr before core collapse, longer than Ne, O, or Si burning phases. Instead, the episodic mass loss must extend back through C burning and perhaps even part of He burning.Comment: 14 pages, 8 figs. accepted in MNRA

Assessing protocol adherence in a clinical trial with ordered treatment regimens: Quantifying the pragmatic, randomized optimal platelet and plasma ratios (PROPPR) trial experience

AbstractBackgroundMedication dispensing errors are common in clinical trials, and have a significant impact on the quality and validity of a trial. Therefore, the definition, calculation and evaluation of such errors are important for supporting a trial’s conclusions. A variety of medication dispensing errors can occur. In this paper, we focus on errors in trials where the intervention includes multiple therapies that must be given in a pre-specified order that varies across treatment arms and varies in duration.MethodsThe Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was a Phase III multi-site, randomized trial to compare the effectiveness and safety of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with a 1:1:2 ratio. In this trial, these three types of blood products were to be transfused in a pre-defined order that differed by treatment arm. In this paper, we present approaches from the PROPPR trial that we used to define and calculate the occurrence of out of order blood transfusion errors. We applied the proposed method to calculate protocol adherence to the specified order of transfusion in each treatment arm.ResultsUsing our proposed method, protocol adherence was greater in the 1:1:1 group than in the 1:1:2 group (96% vs 93%) (p<0.0001), although out of order transfusion errors in both groups were low. Final transfusion ratios of plasma to platelets to red blood cells for the 1:1:1 ratio group was 0.93:1.32:1, while the transfusion ratio for the 1:1:2 ratio group was 0.48:0.48:1.ConclusionsOverall, PROPPR adherence to blood transfusion order pre-specified in the protocol was high, and the required order of transfusions for the 1:1:2 group was more difficult to achieve. The approaches proposed in this manuscript were useful in evaluating the PROPPR adherence and are potentially useful for other trials where a specific treatment orders with varying durations must be maintained

SN2013fs and SN2013fr: Exploring the circumstellar-material diversity in Type II supernovae

We present photometry and spectroscopy of SN2013fs and SN2013fr in the first 100 days post-explosion. Both objects showed transient, relatively narrow H$\alpha$ emission lines characteristic of SNeIIn, but later resembled normal SNeII-P or SNeII-L, indicative of fleeting interaction with circumstellar material (CSM). SN2013fs was discovered within 8hr of explosion. Its light curve exhibits a plateau, with spectra revealing strong CSM interaction at early times. It is a less luminous version of the transitional SNIIn PTF11iqb, further demonstrating a continuum of CSM interaction intensity between SNeII-P and IIn. It requires dense CSM within 6.5$\times$10$^{14}$~cm of the progenitor, from a phase of advanced pre-SN mass loss shortly before explosion. Spectropolarimetry of SN2013fs shows little continuum polarization, but noticeable line polarization during the plateau phase. SN2013fr morphed from a SNIIn at early times to a SNII-L. After the first epoch its narrow lines probably arose from host-galaxy emission, but the bright, narrow H$\alpha$ emission at early times may be intrinsic. As for SN2013fs, this would point to a short-lived phase of strong CSM interaction if proven to be intrinsic, suggesting a continuum between SNeIIn and II-L. It is a low-velocity SNII-L, like SN2009kr but more luminous. SN2013fr also developed an IR excess at later times, due to warm CSM dust that require a more sustained phase of strong pre-SN mass loss.Comment: MNRAS accepted. 28 pages, 23 figures, 8 table

C-Reactive Protein Gene Variants Are Associated with Postoperative C-reactive Protein Levels After Coronary Artery Bypass Surgery

Background: Elevated baseline C-reactive protein (CRP) levels are associated with increased risk for developing cardiovascular disease. Several CRP gene variants have been associated with altered baseline CRP levels in ambulatory populations. However, the influence of CRP gene variants on CRP levels during inflammatory states, such as surgery, is largely unexplored. We describe the association between candidate CRP gene variants and postoperative plasma CRP levels in patients undergoing primary, elective coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). Methods: Using a multicenter candidate gene association study design, we examined the association between seventeen candidate CRP single nucleotide polymorphisms (SNPs) and inferred haplotypes, and altered postoperative CRP levels in 604 patients undergoing CABG surgery with CPB. Perioperative CRP levels were measured immediately prior to surgery, post-CPB and on postoperative days (POD) 1–4. Results: CRP levels were significantly elevated at all postoperative time points when compared with preoperative levels (P < 0.0001). After adjusting for clinical covariates, the minor allele of the synonymous coding SNP, rs1800947 was associated with lower peak postoperative CRP levels ($P = 2.4 × 10^{-4}$) and lower CRP levels across all postoperative time points ($P = 4.8 × 10^{-5}$). rs1800947 remained highly significant after Bonferroni adjustment for multiple comparisons. Conclusion: We identified a CRP gene SNP associated with lower postoperative CRP levels in patients undergoing CABG surgery with CPB. Further investigation is needed to clarify the significance of this association between CRP gene variants and the acute-phase rise in postoperative CRP levels with regard to the risk of adverse postoperative outcomes

Early deprivation alters structural brain development from middle childhood to adolescence

Hypotheses concerning the biologic embedding of early adversity via developmental neuroplasticity mechanisms have been proposed on the basis of experimental studies in animals. However, no studies have demonstrated a causal link between early adversity and neural development in humans. Here, we present evidence from a randomized controlled trial linking psychosocial deprivation in early childhood to changes in cortical development from childhood to adolescence using longitudinal data from the Bucharest Early Intervention Project. Changes in cortical structure due to randomization to foster care were most pronounced in the lateral and medial prefrontal cortex and in white matter tracts connecting the prefrontal and parietal cortex. Demonstrating the causal impact of exposure to deprivation on the development of neural structure highlights the importance of early placement into family-based care to mitigate lasting neurodevelopmental consequences associated with early-life deprivation

Adolescent Medicine at the Crossroads: A Review of Fellowship Training and Recommendations for Reform

This report examines the current state of adolescent medicine fellowship programs -- including the supply and recruitment of fellows; the nature and content of clinical, research, and leadership training; and the institutional and financial challenges facing training programs today -- and offers recommendations for building the field. The report is based on findings from the first comprehensive national survey of adolescent medicine fellowship program directors, conducted in the spring of 2007 by Incenter Strategies. The document also presents selected findings from two other Incenter Strategies’ surveys conducted in 2007: one of pediatric residency program directors and the other of adolescent medicine faculty responsible for the one-month pediatric residency rotation. In addition, the report presents findings from key informant interviews and an extensive literature review

Towards the Development of Peptide Nanfilaments and Nanoropes as Smart Materials

Protein design studies using coiled coils have illustrated the potential of engineering simple peptides to self-associate into polymers and networks. Although basic aspects of self-assembly in protein systems have been demonstrated, it remains a major challenge to create materials whose large-scale structures are well determined from design of local protein–protein interactions. Here, we show the design and characterization of a helical peptide, which uses phased hydrophobic interactions to drive assembly into nanofilaments and fibrils (“nanoropes”). Using the hydrophobic effect to drive self-assembly circumvents problems of uncontrolled self-assembly seen in previous approaches that used electrostatics as a mode for self-assembly. The nanostructures designed here are characterized by biophysical methods including analytical ultracentrifugation, dynamic light scattering, and circular dichroism to measure their solution properties, and atomic force microscopy to study their behavior on surfaces. Additionally, the assembly of such structures can be predictably regulated by using various environmental factors, such as pH, salt, other molecular crowding reagents, and specifically designed “capping” peptides. This ability to regulate self-assembly is a critical feature in creating smart peptide biomaterials