Dynamic Functional Connectivity in Pediatric Mild Traumatic Brain Injury.

Resting-state fMRI can be used to identify recurrent oscillatory patterns of functional connectivity within the human brain, also known as dynamic brain states. Alterations in dynamic brain states are highly likely to occur following pediatric mild traumatic brain injury (pmTBI) due to the active developmental changes. The current study used resting-state fMRI to investigate dynamic brain states in 200 patients with pmTBI (ages 8-18 years, median = 14 years) at the subacute (∼1-week post-injury) and early chronic (∼ 4 months post-injury) stages, and in 179 age- and sex-matched healthy controls (HC). A k-means clustering analysis was applied to the dominant time-varying phase coherence patterns to obtain dynamic brain states. In addition, correlations between brain signals were computed as measures of static functional connectivity. Dynamic connectivity analyses showed that patients with pmTBI spend less time in a frontotemporal default mode/limbic brain state, with no evidence of change as a function of recovery post-injury. Consistent with models showing traumatic strain convergence in deep grey matter and midline regions, static interhemispheric connectivity was affected between the left and right precuneus and thalamus, and between the right supplementary motor area and contralateral cerebellum. Changes in static or dynamic connectivity were not related to symptom burden or injury severity measures, such as loss of consciousness and post-traumatic amnesia. In aggregate, our study shows that brain dynamics are altered up to 4 months after pmTBI, in brain areas that are known to be vulnerable to TBI. Future longitudinal studies are warranted to examine the significance of our findings in terms of long-term neurodevelopment.

Neural correlates of cognitive control deficits in pediatric mild traumatic brain injury.

There is a growing body of research showing that cerebral pathophysiological processes triggered by pediatric mild traumatic brain injury (pmTBI) may extend beyond the usual clinical recovery timeline. It is paramount to further unravel these processes, because the possible long-term cognitive effects resulting from ongoing secondary injury in the developing brain are not known. In the current fMRI study, neural processes related to cognitive control were studied in 181 patients with pmTBI at sub-acute (SA; ~1 week) and early chronic (EC; ~4 months) stages post-injury. Additionally, a group of 162 age- and sex-matched healthy controls (HC) were recruited at equivalent time points. Proactive (post-cue) and reactive (post-probe) cognitive control were examined using a multimodal attention fMRI paradigm for either congruent or incongruent stimuli. To study brain network function, the triple-network model was used, consisting of the executive and salience networks (collectively known as the cognitive control network), and the default mode network. Additionally, whole-brain voxel-wise analyses were performed. Decreased deactivation was found within the default mode network at the EC stage following pmTBI during both proactive and reactive control. Voxel-wise analyses revealed sub-acute hypoactivation of a frontal area of the cognitive control network (left pre-supplementary motor area) during proactive control, with a reversed effect at the EC stage after pmTBI. Similar effects were observed in areas outside of the triple-network during reactive control. Group differences in activation during proactive control were limited to the visual domain, whereas for reactive control findings were more pronounced during the attendance of auditory stimuli. No significant correlations were present between task-related activations and (persistent) post-concussive symptoms. In aggregate, current results show alterations in neural functioning during cognitive control in pmTBI up to 4 months post-injury, regardless of clinical recovery. We propose that subacute decreases in activity reflect a general state of hypo-excitability due to the injury, while early chronic hyperactivation represents a compensatory mechanism to prevent default mode interference and to retain cognitive control.

Photo-Responsive Control of Adsorption and Structure Formation at the Air-Water Interface with Arylazopyrazoles.

Smart interfaces that are responsive to external triggers such as light are of great interest for the development of responsive or adaptive materials and interfaces. Using alkyl-arylazopyrazole butyl sulfonate surfactants (alkyl-AAP) that can undergo E/Z photoisomerization when irradiated with green (E) and UV (Z) lights, we demonstrate through a combination of experiments and computer simulations that there can be surprisingly large changes in surface tension and in the molecular structure and order at air-water interfaces. Surface tensiometry, vibrational sum-frequency generation (SFG) spectroscopy, and neutron reflectometry (NR) are applied to the study of custom-synthesized AAP surfactants with octyl- and H-terminal groups at air-water interfaces as a function of their bulk concentration and E/Z configuration. Upon photoswitching, a drastic influence of the alkyl chain on both the surface activity and the responsiveness of interfacial surfactants is revealed from changes in the surface tension, γ, where the largest changes in γ are observed for octyl-AAP (Δγ ∼ 23 mN/m) in contrast to H-AAP with Δγ < 10 mN/m. Results from vibrational SFG spectroscopy and NR show that the interfacial composition and the molecular order of the surfactants drastically change with E/Z photoisomerization and surface coverage. Indeed, from analysis of the S-O (head group) and C-H vibrational bands (hydrophobic tail), a qualitative analysis of orientational and structural changes of interfacial AAP surfactants is provided. The experiments are complemented by resolution of thermodynamic parameters such as equilibrium constants from ultra-coarse-grained simulations, which also capture details like island formation and interaction parameters of interfacial molecules. Here, the interparticle interaction ("stickiness") and the interaction with the surface are adjusted, closely reflecting experimental conditions.

Effects of Charge Density on Spread Hyperbranched Polyelectrolyte/Surfactant Films at the Air/Water Interface.

The interfacial structure and morphology of films spread from hyperbranched polyethylene imine/sodium dodecyl sulfate (PEI/SDS) aggregates at the air/water interface have been resolved for the first time with respect to polyelectrolyte charged density. A recently developed method to form efficient films from the dissociation of aggregates using a minimal quantity of materials is exploited as a step forward in enhancing understanding of the film properties with a view to their future use in technological applications. Interfacial techniques that resolve different time and length scales, namely, ellipsometry, Brewster angle microscopy, and neutron reflectometry, are used. Extended structures of both components are formed under a monolayer of the surfactant with bound polyelectrolytes upon film compression on subphases adjusted to pH 4 or 10, corresponding to high and low charge density of the polyelectrolyte, respectively. A rigid film is related to compact conformation of the PEI in the interfacial structure at pH 4, while it is observed that aggregates remain embedded in mobile films at pH 10. The ability to compact surfactants in the monolayer to the same extent as its maximum coverage in the absence of polyelectrolyte is distinct from the behavior observed for spread films involving linear polyelectrolytes, and intriguingly evidence points to the formation of extended structures over the full range of surface pressures. We conclude that the molecular architecture and charge density can be important parameters in controlling the structures and properties of spread polyelectrolyte/surfactant films, which holds relevance to a range of applications, such as those where PEI is used, including CO2 capture, electronic devices, and gene transfection.

Multicompartmental models and diffusion abnormalities in paediatric mild traumatic brain injury.

The underlying pathophysiology of paediatric mild traumatic brain injury and the time-course for biological recovery remains widely debated, with clinical care principally informed by subjective self-report. Similarly, clinical evidence indicates that adolescence is a risk factor for prolonged recovery, but the impact of age-at-injury on biomarkers has not been determined in large, homogeneous samples. The current study collected diffusion MRI data in consecutively recruited patients (n = 203; 8-18 years old) and age and sex-matched healthy controls (n = 170) in a prospective cohort design. Patients were evaluated subacutely (1-11 days post-injury) as well as at 4 months post-injury (early chronic phase). Healthy participants were evaluated at similar times to control for neurodevelopment and practice effects. Clinical findings indicated persistent symptoms at 4 months for a significant minority of patients (22%), along with residual executive dysfunction and verbal memory deficits. Results indicated increased fractional anisotropy and reduced mean diffusivity for patients, with abnormalities persisting up to 4 months post-injury. Multicompartmental geometric models indicated that estimates of intracellular volume fractions were increased in patients, whereas estimates of free water fractions were decreased. Critically, unique areas of white matter pathology (increased free water fractions or increased neurite dispersion) were observed when standard assumptions regarding parallel diffusivity were altered in multicompartmental models to be more biologically plausible. Cross-validation analyses indicated that some diffusion findings were more reproducible when ∼70% of the total sample (142 patients, 119 controls) were used in analyses, highlighting the need for large-sample sizes to detect abnormalities. Supervised machine learning approaches (random forests) indicated that diffusion abnormalities increased overall diagnostic accuracy (patients versus controls) by ∼10% after controlling for current clinical gold standards, with each diffusion metric accounting for only a few unique percentage points. In summary, current results suggest that novel multicompartmental models are more sensitive to paediatric mild traumatic brain injury pathology, and that this sensitivity is increased when using parameters that more accurately reflect diffusion in healthy tissue. Results also indicate that diffusion data may be insufficient to achieve a high degree of objective diagnostic accuracy in patients when used in isolation, which is to be expected given known heterogeneities in pathophysiology, mechanism of injury and even criteria for diagnoses. Finally, current results indicate ongoing clinical and physiological recovery at 4 months post-injury.

Aqueous Radical Initiated Oxidation of an Organic Monolayer at the Air-Water Interface as a Proxy for Thin Films on Atmospheric Aerosol Studied with Neutron Reflectometry.

Neutron reflectometry has been used to study the radical initiated oxidation of a monolayer of the lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) at the air-solution interface by aqueous-phase hydroxyl, sulfate, and nitrate radicals. The oxidation of organic films at the surface of atmospheric aqueous aerosols can influence the optical properties of the aerosol and consequently can impact Earth's radiative balance and contribute to modern climate change. The amount of material at the air-solution interface was found to decrease on exposure to aqueous-phase radicals which was consistent with a multistep degradation mechanism, i.e., the products of reaction of the DSPC film with aqueous radicals were also surface active. The multistep degradation mechanism suggests that lipid molecules in the thin film degrade to form progressively shorter chain surface active products and several reactive steps are required to remove the film from the air-solution interface. Bimolecular rate constants for oxidation via the aqueous phase OH radical cluster around 1010 dm3 mol-1 s-1. Calculations to determine the film lifetime indicate that it will take ∼4-5 days for the film to degrade to 50% of its initial amount in the atmosphere, and therefore attack by aqueous radicals on organic films could be atmospherically important relative to typical atmospheric aerosol lifetimes.

Test-Retest Reliability of a Semi-Structured Interview to Aid in Pediatric Traumatic Brain Injury Diagnosis.

OBJECTIVE: Retrospective self-report is typically used for diagnosing previous pediatric traumatic brain injury (TBI). A new semi-structured interview instrument (New Mexico Assessment of Pediatric TBI; NewMAP TBI) investigated test-retest reliability for TBI characteristics in both the TBI that qualified for study inclusion and for lifetime history of TBI. METHOD: One-hundred and eight-four mTBI (aged 8-18), 156 matched healthy controls (HC), and their parents completed the NewMAP TBI within 11 days (subacute; SA) and 4 months (early chronic; EC) of injury, with a subset returning at 1 year (late chronic; LC). RESULTS: The test-retest reliability of common TBI characteristics [loss of consciousness (LOC), post-traumatic amnesia (PTA), retrograde amnesia, confusion/disorientation] and post-concussion symptoms (PCS) were examined across study visits. Aside from PTA, binary reporting (present/absent) for all TBI characteristics exhibited acceptable (≥0.60) test-retest reliability for both Qualifying and Remote TBIs across all three visits. In contrast, reliability for continuous data (exact duration) was generally unacceptable, with LOC and PCS meeting acceptable criteria at only half of the assessments. Transforming continuous self-report ratings into discrete categories based on injury severity resulted in acceptable reliability. Reliability was not strongly affected by the parent completing the NewMAP TBI. CONCLUSIONS: Categorical reporting of TBI characteristics in children and adolescents can aid clinicians in retrospectively obtaining reliable estimates of TBI severity up to a year post-injury. However, test-retest reliability is strongly impacted by the initial data distribution, selected statistical methods, and potentially by patient difficulty in distinguishing among conceptually similar medical concepts (i.e., PTA vs. confusion).

Severity of Ongoing Post-Concussive Symptoms as a Predictor of Cognitive Performance Following a Pediatric Mild Traumatic Brain Injury.

OBJECTIVE: This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury. METHOD: 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8-18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1-11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (~4 months) phase. RESULTS: Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not. CONCLUSIONS: The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.

Resting-State Power and Regional Connectivity After Pediatric Mild Traumatic Brain Injury.

BACKGROUND: Physiological recovery from pediatric mild traumatic brain injury (pmTBI) as a function of age remains actively debated, with the majority of studies relying on subjective symptom report rather than objective markers of brain physiology. PURPOSE: To examine potential abnormalities in fractional amplitude of low-frequency fluctuations (fALFF) or regional homogeniety (ReHo) during resting-state fMRI following pmTBI. STUDY TYPE: Prospective cohort. POPULATION: Consecutively recruited pmTBI (N = 105; 8-18 years old) and age- and sex-matched healthy controls (HC; N = 113). FIELD STRENGTH/SEQUENCE: 3T multiecho gradient T1 -weighted and single-shot gradient-echo echo-planar imaging. ASSESSMENT: All pmTBI participants were assessed 1 week and 4 months postinjury (HC assessed at equivalent timepoints after the first visit). Comprehensive demographic, clinical, and cognitive batteries were performed in addition to primary investigation of fALFF and ReHo. All pmTBI were classified as "persistent" or "recovered" based on both assessment periods. STATISTICAL TESTS: Chi-square, nonparametric, and generalized linear models for demographic data. Generalized estimating equations for clinical and cognitive data. Voxelwise general linear models (AFNI's 3dMVM) for fALFF and ReHo assessment. RESULTS: Evidence of recovery was observed for some, but not all, clinical and cognitive measures at 4 months postinjury. fALFF was increased in the left striatum for pmTBI relative to HC both at 1 week and 4 months postinjury; whereas no significant group differences (P > 0.001) were observed for ReHo. Age-at-injury did not moderate either resting-state metric across groups. In contrast to analyses of pmTBI as a whole, there were no significant (P > 0.001) differences in either fALFF or ReHo in patients with persistent postconcussive symptoms compared to recovered patients and controls at 4 months postinjury. DATA CONCLUSIONS: Our findings suggest prolonged clinical recovery and alterations in the relative amplitude of resting-state fluctuations up to 4 months postinjury, but no clear relationship with age-at-injury or subjective symptom report. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 2 J. MAGN. RESON. IMAGING 2020;52:1701-1713.

The reaction of oleic acid monolayers with gas-phase ozone at the air water interface: the effect of sub-phase viscosity, and inert secondary components.

Organic films that form on atmospheric particulate matter change the optical and cloud condensation nucleation properties of the particulate matter and consequently have implications for modern climate and climate models. The organic films are subject to attack from gas-phase oxidants present in ambient air. Here we revisit in greater detail the oxidation of a monolayer of oleic acid by gas-phase ozone at the air-water interface as this provides a model system for the oxidation reactions that occur at the air-water interface of aqueous atmospheric aerosol. Experiments were performed on monolayers of oleic acid at the air-liquid interface at atmospherically relevant ozone concentrations to investigate if the viscosity of the sub-phase influences the rate of the reaction and to determine the effect of the presence of a second component within the monolayer, stearic acid, which is generally considered to be non-reactive towards ozone, on the reaction kinetics as determined by neutron reflectometry measurements. Atmospheric aerosol can be extremely viscous. The kinetics of the reaction were found to be independent of the viscosity of the sub-phase below the monolayer over a range of moderate viscosities, , demonstrating no involvement of aqueous sub-phase oxidants in the rate determining step. The kinetics of oxidation of monolayers of pure oleic acid were found to depend on the surface coverage with different behaviour observed above and below a surface coverage of oleic acid of ∼1 × 1018 molecule m-2. Atmospheric aerosol are typically complex mixtures, and the presence of an additional compound in the monolayer that is inert to direct ozone oxidation, stearic acid, did not significantly change the reaction kinetics. It is demonstrated that oleic acid monolayers at the air-water interface do not leave any detectable material at the air-water interface, contradicting the previous work published in this journal which the authors now believe to be erroneous. The combined results presented here indicate that the kinetics, and thus the atmospheric chemical lifetime for unsaturated surface active materials at the air-water interface to loss by reaction with gas-phase ozone, can be considered to be independent of other materials present at either the air-water interface or in the aqueous sub-phase.

Neurosensory Screening and Symptom Provocation in Pediatric Mild Traumatic Brain Injury.

OBJECTIVE: To evaluate diagnostic/prognostic implications of neurosensory testing during the subacute stage in patients with pediatric mild traumatic brain injury (pmTBI). SETTING: Recruitment from pediatric emergency department and urgent care clinics, assessment in a controlled environment. PARTICIPANTS: In total, 146 pmTBI patients evaluated 7.4 ± 2.3 days and approximately 4 months postinjury; 104 age/sex-matched healthy controls (HCs) at equivalent time points. DESIGN: Prospective cohort study. MAIN MEASURES: Neurosensory examination based on sequence of 10 established tests of vestibular-ocular, oculomotor, vestibulospinal, and visual functioning. RESULTS: The amount of symptom provocation (positive change from pretest symptomatology) was significantly increased in pmTBI relative to HCs on every subtest 1 week postinjury, as were deficits in monocular accommodative amplitude and King-Devick Test errors. However, symptom provocation did not meaningfully alter diagnostic sensitivity/specificity relative to more easily obtained pretest symptom ratings. Evidence of clinically significant symptom provocation 1 week postinjury improved sensitivity (Δ = +12.9%) of identifying patients with persistent postconcussive symptoms 4 months postinjury on an independent symptom measure. CONCLUSIONS: The diagnostic sensitivity/specificity of neurosensory testing in acutely concussed youth may be limited at 1 week postinjury as a function of natural recovery occurring in most emergency department cohorts. Neurosensory screening may have greater utility for identifying patients who experience delayed recovery.

Proactive inhibition deficits with normal perfusion after pediatric mild traumatic brain injury.

Although much attention has been generated in popular media regarding the deleterious effects of pediatric mild traumatic brain injury (pmTBI), a paucity of empirical evidence exists regarding the natural course of biological recovery. Fifty pmTBI patients (12-18 years old) were consecutively recruited from Emergency Departments and seen approximately 1 week and 4 months post-injury in this prospective cohort study. Data from 53 sex- and age-matched healthy controls (HC) were also collected. Functional magnetic resonance imaging was obtained during proactive response inhibition and at rest, in conjunction with independent measures of resting cerebral blood flow. High temporal resolution imaging enabled separate modeling of neural responses for preparation and execution of proactive response inhibition. A priori predictions of failed inhibitory responses (i.e., hyperactivation) were observed in motor circuitry (pmTBI>HC) and sensory areas sub-acutely and at 4 months post-injury. Paradoxically, pmTBI demonstrated hypoactivation (HC>pmTBI) during target processing, along with decreased activation within prefrontal cognitive control areas. Functional connectivity within motor circuitry at rest suggested that deficits were limited to engagement during the inhibitory task, whereas normal resting cerebral perfusion ruled out deficits in basal perfusion. In conclusion, current results suggest blood oxygen-level dependent deficits during inhibitory control may exceed commonly held beliefs about physiological recovery following pmTBI, potentially lasting up to 4 months post-injury.

Bayesian determination of the effect of a deep eutectic solvent on the structure of lipid monolayers.

In this work, we present the first example of the self-assembly of phospholipid monolayers at the interface between air and an ionic solvent. Deep eutectic solvents are a novel class of environmentally friendly, non-aqueous, room temperature liquids with tunable properties, that have wide-ranging potential applications and are capable of promoting the self-assembly of surfactant molecules. We use a chemically-consistent Bayesian modelling of X-ray and neutron reflectometry measurements to show that these monolayers broadly behave as they do on water. This method allows for the monolayer structure to be determined, alongside the molecular volumes of the individual monolayer components, without the need for water-specific constraints to be introduced. Furthermore, using this method we are able to better understand the correlations present between parameters in the analytical model. This example of a non-aqueous phospholipid monolayer has important implications for the potential uses of these solvents and for our understanding of how biomolecules behave in the absence of water.

Reflectometry Reveals Accumulation of Surfactant Impurities at Bare Oil/Water Interfaces.

Bare interfaces between water and hydrophobic media like air or oil are of fundamental scientific interest and of great relevance for numerous applications. A number of observations involving water/hydrophobic interfaces have, however, eluded a consensus mechanistic interpretation so far. Recent theoretical studies ascribe these phenomena to an interfacial accumulation of charged surfactant impurities in water. In the present work, we show that identifying surfactant accumulation with X-ray reflectometry (XRR) or neutron reflectometry (NR) is challenging under conventional contrast configurations because interfacial surfactant layers are then hardly visible. On the other hand, both XRR and NR become more sensitive to surfactant accumulation when a suitable scattering length contrast is generated by using fluorinated oil. With this approach, significant interfacial accumulation of surfactant impurities at the bare oil/water interface is observed in experiments involving standard cleaning procedures. These results suggest that surfactant impurities may be a limiting factor for the investigation of fundamental phenomena involving water/hydrophobic interfaces.

A Versatile Method for the Distance-Dependent Structural Characterization of Interacting Soft Interfaces by Neutron Reflectometry.

Interactions between soft interfaces govern the behavior of emulsions and foams and crucially influence the functions of biological entities like membranes. To understand the character of these interactions, detailed insight into the interfaces' structural response in terms of molecular arrangements and conformations is often essential. This requires the realization of controlled interaction conditions and surface-sensitive techniques capable of resolving the structure of buried interfaces. Here, we present a new approach to determine the distance-dependent structure of interacting soft interfaces by neutron reflectometry. A solid/water interface and a water/oil interface are functionalized independently and initially macroscopically separated. They are then brought into contact and structurally characterized under interacting conditions. The nanometric distance between the two interfaces can be varied via the exertion of osmotic pressures. Our first experiments on lipid-anchored polymer brushes interacting across water with solid-grafted polyelectrolyte brushes and with bare silicon surfaces reveal qualitatively different interaction scenarios depending on the chemical composition of the two involved interfaces.

Effects of Aggregate Charge and Subphase Ionic Strength on the Properties of Spread Polyelectrolyte/Surfactant Films at the Air/Water Interface under Static and Dynamic Conditions.

We demonstrate the ability to tune the formation of extended structures in films of poly(sodium styrenesulfonate)/dodecyltrimethylammonium bromide at the air/water interface through control over the charge/structure of aggregates as well as the ionic strength of the subphase. Our methodology to prepare loaded polyelectrolyte/surfactant films from self-assembled liquid crystalline aggregates exploits their fast dissociation and Marangoni spreading of material upon contact with an aqueous subphase. This process is proposed as a potential new route to prepare cheap biocompatible films for transfer applications. We show that films spread on water from swollen aggregates of low/negative charge have 1:1 charge binding and can be compressed only to a monolayer, beyond which material is lost to the bulk. For films spread on water from compact aggregates of positive charge, however, extended structures of the two components are created upon spreading or upon compression of the film beyond a monolayer. The application of ellipsometry, Brewster angle microscopy, and neutron reflectometry as well as measurements of surface pressure isotherms allow us to reason that formation of extended structures is activated by aggregates embedded in the film. The situation upon spreading on 0.1 M NaCl is different as there is a high concentration of small ions that stabilize loops of the polyelectrolyte upon film compression, yet extended structures of both components are only transient. Analogy of the controlled formation of extended structures in fluid monolayers is made to reservoir dynamics in lung surfactant. The work opens up the possibility to control such film dynamics in related systems through the rational design of particles in the future.

Adsorption of Denaturated Lysozyme at the Air-Water Interface: Structure and Morphology.

The application of protein deuteration and high flux neutron reflectometry has allowed a comparison of the adsorption properties of lysozyme at the air-water interface from dilute solutions in the absence and presence of high concentrations of two strong denaturants: urea and guanidine hydrochloride (GuHCl). The surface excess and adsorption layer thickness were resolved and complemented by images of the mesoscopic lateral morphology from Brewster angle microscopy. It was revealed that the thickness of the adsorption layer in the absence of added denaturants is less than the short axial length of the lysozyme molecule, which indicates deformation of the globules at the interface. Two-dimensional elongated aggregates in the surface layer merge over time to form an extensive network at the approach to steady state. Addition of denaturants in the bulk results in an acceleration of adsorption and an increase of the adsorption layer thickness. These results are attributed to incomplete collapse of the globules in the bulk from the effects of the denaturants as a result of interactions between remote amino acid residues. Both effects may be connected to an increase of the effective total volume of macromolecules due to the changes of their tertiary structure, that is, the formation of molten globules under the influence of urea and the partial unfolding of globules under the influence of GuHCl. In the former case, the increase of globule hydrophobicity leads to cooperative aggregation in the surface layer during adsorption. Unlike in the case of solutions without denaturants, the surface aggregates are short and wormlike, their size does not change with time, and they do not merge to form an extensive network at the approach to steady state. To the best of our knowledge, these are the first observations of cooperative aggregation in lysozyme adsorption layers.

Attention-Deficit/Hyperactivity Disorder (ADHD): Interaction between socioeconomic status and parental history of ADHD determines prevalence.

BACKGROUND: Many studies have reported a higher prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) among disadvantaged populations, but few have considered how parental history of ADHD might modify that relationship. We evaluated whether the prevalence of ADHD varies by socioeconomic status (SES) and parental history of ADHD in a population-sample of elementary school children age 6-14 years. METHODS: We screened all children in grades 1-5 in 17 schools in one North Carolina (U.S.) county for ADHD using teacher rating scales and 1,160 parent interviews, including an ADHD structured interview (DISC). We combined parent and teacher ratings to determine DSM-IV ADHD status. Data analysis was restricted to 967 children with information about parental history of ADHD. SES was measured by family income and respondent education. RESULTS: We found an interaction between family income and parental history of ADHD diagnosis (p = .016). The SES gradient was stronger in families without a parental history and weaker among children with a parental history. Among children without a parental history of ADHD diagnosis, low income children had 6.2 times the odds of ADHD (95% CI 3.4-11.3) as high income children after adjusting for covariates. Among children with a parental history, all had over 10 times the odds of ADHD as high income children without a parental history but the SES gradient between high and low income children was less pronounced [odds ratio (OR) = 1.4, 95% CI 0.6-3.5]. CONCLUSIONS: Socioeconomic status and parental history of ADHD are each strong risk factors for ADHD that interact to determine prevalence. More research is needed to dissect the components of SES that contribute to risk of ADHD. Future ADHD research should evaluate whether the strength of other environmental risk factors vary by parental history. Early identification and interventions for children with low SES or parental histories of ADHD should be explored.

Risk of Concussion During Sports Versus Physical Education Among New Mexico Middle and High School Students.

OBJECTIVES: To measure the risk of concussion among New Mexico middle and high school students during both sports and physical education. METHODS: Athletic directors or athletic trainers in 147 schools were asked to report the number of concussions occurring during sports and physical education in the 2013 to 2014 school year. We calculated 1-year cumulative incidence rates. RESULTS: Of the 147 schools, 99 responded (67%). During the school year, 598 students were removed from athletics because of a concussion, a 1-year cumulative incidence of 3.5 per 100. The concussion rate during sports was 3.0: 3.5 for boys and 2.4 for girls (relative risk [RR] = 1.5; 95% confidence interval [CI] = 1.2, 1.7). An additional 335 students experienced concussions during physical education. Concussion rates during physical education were 60% higher than during sports (RR = 1.6; 95% CI = 1.4, 1.8). CONCLUSIONS: In our data, the risk of concussion was higher in physical education than in sports. This suggests that concussions should be tracked for a wide range of youth athletic activities, not just for sports. Monitoring cumulative incidence, in addition to other measures, may allow comparisons across schools and regions. More prevention efforts are needed.

Towards optimised drug delivery: structure and composition of testosterone enanthate in sodium dodecyl sulfate monolayers.

Surface tension and specular neutron reflectivity measurements have been used, for the first time to systematically study both the interfacial structure and composition of monolayers of the soluble surfactant, sodium dodecyl sulfate containing a low-dose, poorly water soluble drug, testosterone enanthate. Modelling of the specular neutron reflectivity data suggests that the hydrophobic testosterone enanthate was adsorbed in the C12 hydrophobic tail region of the surfactant monolayer, regardless of the concentration of surfactant at the interface and whether or not additional drug was added to the interface. The location of the hydrophobic drug in the tail region of the surfactant monolayer is supported by the results of classical, large-scale molecular dynamics simulations. The thickness of the surfactant monolayer obtained, in the presence and absence of drug, using molecular dynamics simulations was in good agreement with the corresponding values obtained from the specular neutron reflectivity measurements. The stoichiometry of surfactant:drug at the air-water interface at sodium dodecyl sulfate concentrations above the critical micelle concentration was determined from specular neutron reflectivity measurements to be approximately 3 : 1, and remained constant after the spreading of further testosterone enanthate at the interface. Significantly, this stoichiometry was the same as that obtained in the micelles from bulk solubilisation studies. Important insights into the preferred location of drug in surfactant monolayers at the air-water interface as well as its effect on the structure of the monolayer have been obtained from our combined use of experimental and simulation techniques.