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.

A Pilot Randomized Controlled Trial Evaluating Essential Oils for Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, debilitating consequence of cancer treatment affecting up to 60% of patients. Pharmacological approaches to CIPN are often ineffective and cause adverse effects. Essential oils are an underutilized non-pharmacological approach to pain reduction. AIMS: To ascertain the efficacy of an essential oil intervention to reduce CIPN. DESIGN: A single-blind, pilot randomized controlled trial. METHODS: Participants (n = 27) were stratified by baseline pain scores and randomized to intervention (n = 13) and placebo groups (n = 14). Participants topically-applied the essential oil intervention or placebo every eight hours for six weeks. Pain was assessed using the Short-Form-McGill Pain Questionnaire-2 weekly and the Visual Analogue Scale daily. Quality-of-life was assessed using the Quality-of-Life: CIPN-20 and Quality-of-Life Adult Cancer Survivor questionnaires. Data were analyzed in SPSS using generalized estimating equations. RESULTS: No significant difference was observed between groups in pain or quality-of-life scores over seven weeks, but improvement was observed in both groups. Participants using the intervention with pain medications showed a significant reduction in pain compared to placebo (p = .001). Educational level (p = .041) and annual income (p = .005) were significant covariates mirroring these social determinates of pain. Older participants felt less negatively about their CIPN (p = .002). Positive placebo effect and spatiotemporal interactions were observed. CONCLUSIONS: This pilot study demonstrated that participants adhered to the intervention for six weeks. Essential oils have potential direct and adjuvant pain-reducing effects and should be studied further.

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).

Validation of a self-report home food availability checklist against in-home food inventories conducted in low-income Black/African American and Hispanic/Latinx households with preschool-age children.

Home food availability (HFA) checklists can be completed by self-report to assess the home food environment. Checklists developed for Black/African American (B/AA) and Hispanic/Latinx (H/L) households are seldom validated against objective approaches such as exhaustive in-home food inventories. This study validated a self-report HFA checklist developed for B/AA and H/L households (n = 97) against researcher-completed HFA checklists verified by exhaustive in-home food inventories. Mean estimates of sensitivity, specificity, and area of the receiver operating curve (ROC), and interrater agreement (Gwet AC1) were calculated to examine the accuracy and agreement of self-reported checklists against direct observation of individual food items. Mean differences in HFA food group scores were compared (self-report vs observed) to examine group-level relative validity. The predictive validity of this self-reported measure on observed scores and dietary intake were also examined with linear regression. The average values for ROC area (average of sensitivity and specificity) ranged from acceptable (0.76 for sweets) to excellent (0.81 for vegetables, fruits). Average interrater agreement values ranged from moderate (0.41-0.60: sweets) to substantial (0.61-0.79: vegetables, fruit, SSBs, savory foods). Self-reported mean scores, compared to observed scores, were higher for vegetables (mean diff: 1.04) and lower for sweets (mean diff: 0.38, p = 0.01), but regression analyses demonstrated that self-reported scores were good predictors of observed scores with absolute error (based on standard deviation of residuals) ranging from ±1.27 to 1.69 points. Self-reported scores also predicted multiple aspects of dietary intake but more so among H/L households. In conclusion, the HFA checklist obtained via self-report performed well based on multiple indicators of validity suggesting that this self-reported measure can be used to assess home food environments among of B/AA and H/L households.

Prognostic accuracy of triage tools for adults with suspected COVID-19 in a prehospital setting: an observational cohort study.

BACKGROUND: Tools proposed to triage patient acuity in COVID-19 infection have only been validated in hospital populations. We estimated the accuracy of five risk-stratification tools recommended to predict severe illness and compared accuracy to existing clinical decision making in a prehospital setting. METHODS: An observational cohort study using linked ambulance service data for patients attended by Emergency Medical Service (EMS) crews in the Yorkshire and Humber region of England between 26 March 2020 and 25 June 2020 was conducted to assess performance of the Pandemic Respiratory Infection Emergency System Triage (PRIEST) tool, National Early Warning Score (NEWS2), WHO algorithm, CRB-65 and Pandemic Medical Early Warning Score (PMEWS) in patients with suspected COVID-19 infection. The primary outcome was death or need for organ support. RESULTS: Of the 7549 patients in our cohort, 17.6% (95% CI 16.8% to 18.5%) experienced the primary outcome. The NEWS2 (National Early Warning Score, version 2), PMEWS, PRIEST tool and WHO algorithm identified patients at risk of adverse outcomes with a high sensitivity (>0.95) and specificity ranging from 0.3 (NEWS2) to 0.41 (PRIEST tool). The high sensitivity of NEWS2 and PMEWS was achieved by using lower thresholds than previously recommended. On index assessment, 65% of patients were transported to hospital and EMS decision to transfer patients achieved a sensitivity of 0.84 (95% CI 0.83 to 0.85) and specificity of 0.39 (95% CI 0.39 to 0.40). CONCLUSION: Use of NEWS2, PMEWS, PRIEST tool and WHO algorithm could improve sensitivity of EMS triage of patients with suspected COVID-19 infection. Use of the PRIEST tool would improve sensitivity of triage without increasing the number of patients conveyed to hospital.

Analysis of Epistasis in Natural Traits Using Model Organisms.

The ability to detect and understand epistasis in natural populations is important for understanding how biological traits are influenced by genetic variation. However, identification and characterization of epistasis in natural populations remains difficult due to statistical issues that arise as a result of multiple comparisons, and the fact that most genetic variants segregate at low allele frequencies. In this review, we discuss how model organisms may be used to manipulate genotypic combinations to power the detection of epistasis as well as test interactions between specific genes. Findings from a number of species indicate that statistical epistasis is pervasive between natural genetic variants. However, the properties of experimental systems that enable analysis of epistasis also constrain extrapolation of these results back into natural populations.

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.

Do Relaxation Exercises Decrease Pain After Arthroscopic Rotator Cuff Repair? A Randomized Controlled Trial.

BACKGROUND: Pain after rotator cuff repair is commonly managed with opioid medications; however, these medications are associated with serious adverse effects. Relaxation exercises represent a potential nonpharmacologic method of pain management that can be easily implemented without substantial adverse effects; however, the effects of relaxation exercises have not been studied in a practical, reproducible protocol after arthroscopic rotator cuff repair. QUESTIONS/PURPOSES: (1) Does performing relaxation exercises after arthroscopic rotator cuff repair (ARCR) decrease pain compared with standard pain management medication? (2) Does performing relaxation exercises after ARCR decrease opioid consumption? (3) What proportion of patients who used the relaxation techniques believed they decreased their pain level, and what proportion continued using these techniques at 2 weeks? (4) Does performing relaxation exercises after ARCR affect shoulder function? METHODS: During the study period, 563 patients were eligible for inclusion; however, only 146 were enrolled, randomized, and postoperatively followed (relaxation group: 74, control group: 72); 68% (384 of 563) of patients were not contacted due to patient and research staff availability. Thirty-three patients were unenrolled preoperatively or immediately postoperatively due to change in operative procedure (such as, only debridement) or patient request; no postoperative data were collected from these patients. Follow-up proportions were similar between the relaxation and control groups (relaxation: 80%, control: 81%; p = 0.90). The relaxation group received and reviewed educational materials consisting of a 5-minute video and an educational pamphlet explaining relaxation breathing techniques, while the control group did not receive relaxation education materials. Patients recorded their pain levels and opioid consumption during the 5 days after ARCR. Patients also completed the American Shoulder and Elbow Surgeons shoulder score preoperatively and 2, 6, 13, 18, and 26 weeks postoperatively. Linear mixed models were created to analyze postoperative pain, opioid consumption measured in morphine milligram equivalents (MMEs), and shoulder function outcomes. A per-protocol approach was used to correct for patients who were enrolled but subsequently underwent other procedures. RESULTS: There was no difference in pain scores between the relaxation and control groups during the first 5 days postoperatively. There was no difference in pain scores at 2 weeks postoperatively between the relaxation and control groups (3.3 ± 3 versus 3.5 ± 2, mean difference -0.22 [95% CI -1.06 to 0.62]; p = 0.60). There was no difference in opioid consumption during the first 5 days postoperatively between the relaxation and control groups. The use of relaxation exercises resulted in lower 2-week narcotics consumption in the relaxation group than in the control group (309 ± 241 MMEs versus 442 ± 307 MMEs, mean difference -133 [95% CI -225 to -42]; p < 0.01). Sixty-two percent (41 of 66) of patients in the relaxation group believed the relaxation exercises decreased their pain levels. Fifty-two percent (34 of 66) were still performing the exercises at 2 weeks postoperatively. During the 6-month follow-up period, there was no difference in shoulder function between the relaxation and control groups. CONCLUSION: The preoperative administration of quick, basic relaxation exercises allowed patients to use appreciably lower opioid analgesic doses over the first 2 weeks after ARCR, without any worsening of pain scores. We consider this result promising but preliminary; it is possible that a more intense mindfulness intervention-the one we studied here was disseminated using only a 5-minute video-would deliver reductions in pain and further reductions in opioid usage. LEVEL OF EVIDENCE: Level II, therapeutic study.

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.

Are Patient and Surgeon Expectations after ACL Reconstruction Realistic?

BACKGROUND: Patient expectations may affect their satisfaction and functional outcomes after treatment of musculoskeletal injuries. Although there is evidence that patient expectations of ACL reconstruction (ACLR) are inflated, there is limited knowledge about the relationship between physician and patient expectations and patient outcomes after they completely recover from ACLR. Furthermore, it is unclear if specific patient factors influence these expectations. QUESTIONS/PURPOSES: (1) Are patient and surgeon expectations of knee function 18 months after ACLR similar? (2) Are patients' and surgeons' expectations of outcomes similar to patients' actual 2-year outcomes? (3) Is there a relationship between preoperative or intraoperative parameters and expectations? (4) Is there a relationship between preoperative or intraoperative parameters and 2-year ACLR outcomes? METHODS: One-hundred twenty-nine patients undergoing primary ACLR were prospectively enrolled in this study, with 98 (76%) completing 2-year follow-up. Patients completed the IKDC Subjective Knee Evaluation preoperatively and at 3, 6, 12, and 24 months postoperatively. Patients also completed the same questionnaires preoperatively to evaluate expected knee function 18 months after surgery. Immediately postoperatively, surgeons completed the same questionnaires regarding the expected postoperative outcome at 18 months postoperative. Preoperative and intraoperative data were collected to determine an association between expectations and outcomes. Nonparametric analysis was performed using the Mann-Whitney U test, the paired Wilcoxon signed ranks tests and Spearman's correlations, as applicable. RESULTS: There was no difference between patient and surgeon expectations (patient, 94.8 [range 47.4-100] versus surgeon, 94.3 [range 46-100]; p = 0.283), and there was no correlation between higher patient expectations and higher surgeon expectations (r = 0.168, p = 0.078). Patient and surgeon expectations were greater than the actual postoperative outcomes (2-year postoperative: 89.7 [range 32.2 to 100]; p < 0.0001); however, the differences are unlikely to be perceived. There was no correlation between higher 2-year postoperative outcomes and higher patient expectations (r = 0.14, p = 0.186) or higher surgeon expectations (r = 0.019, p = 0.86). Arthroscopic evidence of cartilage damage was independently associated with the worst patient and surgeon expectations. The surgeons themselves were also independently associated with surgeon expectation (p < 0.001). No parameters were associated with postoperative outcomes. CONCLUSIONS: There are no clinically significant differences between surgeon expectations, patient expectations, and 2-year actual outcomes. However, there is also no correlation between the patient expectations, surgeon expectations, and actual outcomes. Although expectations are similar to actual outcomes for most patients, surgeons are unable to accurately predict outcomes for specific patients; thus, preventing adequate patient counseling. Surgeons should be cautious when evaluating and counseling patients preoperatively and avoid assuming high expectations. LEVEL OF EVIDENCE: Level II, therapeutic study.

Modeling of a negative feedback mechanism explains antagonistic pleiotropy in reproduction in domesticated Caenorhabditis elegans strains.

Most biological traits and common diseases have a strong but complex genetic basis, controlled by large numbers of genetic variants with small contributions to a trait or disease risk. The effect-size of most genetic variants is not absolute and is instead dependent upon multiple factors such as the age and genetic background of an organism. In order to understand the mechanistic basis of these changes, we characterized heritable trait differences between two domesticated strains of C. elegans. We previously identified a major effect locus, caused in part by a mutation in a component of the NURF chromatin remodeling complex, that regulates reproductive output in an age-dependent manner. The effect-size of this locus changes from positive to negative over the course of an animal's reproductive lifespan. Here, we use a previously published macroscale model of the egg-laying rate in C. elegans to show that time-dependent effect-size is explained by an unequal use of sperm combined with negative feedback between sperm and ovulation rate. We validate key predictions of this model with controlled mating experiments and quantification of oogenesis and sperm use. Incorporation of this model into QTL mapping allows us to identify and partition new QTLs into specific aspects of the egg-laying process. Finally, we show how epistasis between two genetic variants is predicted by this modeling as a consequence of the unequal use of sperm. This work demonstrates how modeling of multicellular communication systems can improve our ability to predict and understand the role of genetic variation on a complex phenotype. Negative autoregulatory feedback loops, common in transcriptional regulation, could play an important role in modifying genetic architecture in other traits.

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.