Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning.

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk.

Alumina Incorporation in Self-Supported Poly(ethylenimine) Sorbents for Direct Air Capture.

Self-supported branched poly(ethylenimine) scaffolds with ordered macropores are synthesized with and without Al2O3 powder additive by cross-linking poly(ethylenimine) (PEI) with poly(ethylene glycol) diglycidyl ether (PEGDGE) at -196 °C. The scaffolds' CO2 uptake performance is compared with a conventional sorbent, i.e., PEI impregnated on an Al2O3 support. PEI scaffolds with Al2O3 additive show narrow pore size distribution and thinner pore walls than alumina-free materials, facilitating higher CO2 uptake at conditions relevant to direct air capture. The PEI scaffold containing 6.5 wt % Al2O3 had the highest CO2 uptake of 1.23 mmol/g of sorbent under 50% RH 400 ppm of CO2 conditions. In situ DRIFT spectroscopy and temperature-programmed desorption experiments show a significant CO2 uptake contribution via physisorption as well as carbamic acid formation, with lower CO2 binding energies in PEI scaffolds relative to conventional PEI sorbents, likely a result of a lower population of primary amines due to the amine cross-linking reactions during scaffold synthesis. The PEI scaffold containing 6.5 wt % Al2O3 is estimated to have the lowest desorption energy penalty under humid conditions, 4.6 GJ/tCO2, among the sorbents studied.

The dynamic responses of mood and sleep physiology to chronic sleep restriction and subsequent recovery sleep.

Healthy sleep of sufficient duration preserves mood and disturbed sleep is a risk factor for a range of psychiatric disorders. As adults commonly experience chronic sleep restriction (SR), an enhanced understanding of the dynamic relationship between sleep and mood is needed, including whether susceptibility to SR-induced mood disturbance differs between sexes. To address these gaps, data from N=221 healthy adults who completed one of two multi-day laboratory studies with identical 9-day SR protocols were analyzed. Participants randomized to the SR (n=205) condition underwent 5 nights of SR to 4 h time-in-bed and were then randomized to one of seven sleep doses that ranged from 0 h to 12 h in 2 h increments; participants randomized to the control (n=16) condition received 10 h time-in-bed on all study nights. The Profile of Mood States (POMS) was used to assess mood every 2 h during wakefulness and markers of sleep homeostasis (EEG slow-wave activity) were derived via polysomnography. Mood progressively deteriorated across SR with marked disturbances in somatic mood components. Altered sleep physiology contributed to mood disturbance whereby increased EEG slow-wave activity was associated with increased POMS Total Mood Disturbance scores, a finding specific to males. Mood was restored in a dose-response fashion where improvements were greater with longer sleep doses. These findings suggest that when lifestyle and environmental factors are inhibited in the laboratory, the affective consequences of chronic sleep loss are primarily somatic mood disturbances. Altered sleep homeostasis may contribute to mood disturbance, yet sleep-dependent mechanisms may be sex-specific.

Fine-scale foraging ecology and habitat use of sympatric green and hawksbill turtles in the Western Indian ocean.

Using stable isotope analysis of carbon and nitrogen of turtle tissues and putative prey items, we investigated the diet of immature green turtles and hawksbill turtles foraging in the lagoon of Aldabra Atoll, a relatively undisturbed atoll in the southern Seychelles. Aldabra offers a unique environment for understanding sea turtle ecology. Green turtles mostly consumed seagrass and brown algae while hawksbill turtles mainly consumed mangroves and invertebrates. Green turtles showed a dietary shift with size (a proxy for age). There was minimal niche overlap between species and evidence of small-scale foraging site fidelity with turtle tissue reflecting site-specific prey. This highlights the ecological importance of seagrass and mangrove habitats and suggests that turtles play a role in controlling algal biomass at Aldabra. This study is the first to closely examine the foraging ecology of these sympatric turtle species in the Western Indian Ocean, a globally important region for both species.

Sex differences in response inhibition-related neural predictors of PTSD in recent trauma-exposed civilians.

BACKGROUND: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as mechanism for PTSD development, but studies on the potential sex differences of this neurobiological mechanism and how it relates to PTSD severity and progression are sparse. Here we examined sex differences in neural activation during response inhibition and PTSD following recent trauma. METHODS: Participants (N= 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2-weeks and 6-months post-trauma. A Go/NoGo task was performed 2-weeks post-trauma in a 3T MRI scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex (vmPFC), right inferior frontal gyrus (rIFG), and the bilateral hippocampus. General Linear models were used to examine the interaction effect of sex on the relationship between our regions of interest (ROIs) and the whole brain, and PTSD symptoms at 6-months, and symptom progression between 2-weeks and 6-months. RESULTS: Lower response-inhibition-related vmPFC activation 2-weeks post-trauma predicted more PTSD symptoms at 6-months in females but not in males, while greater response-inhibition-related rIFG activation predicted lower PTSD symptom progression in males but not females. Whole brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus. CONCLUSIONS: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions.

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.

Isomorphous Substitution in ZSM-5 in Tandem Methanol/Zeolite Catalysts for the Hydrogenation of CO2 to Aromatics.

Intensified reactors for conversion of CO2 to methanol (via hydrogenation) using metal oxide catalysts coupled with methanol conversion to aromatics in the presence of zeolites (e.g., H-ZSM-5) in a single step are investigated. Brønsted acid sites (BAS) in H-ZSM-5 are important sites in methanol aromatization reactions, and correlations of the reactivity with zeolite acid properties can guide reaction optimization. A classical way of tuning the acidity of zeolites is via the effect of the isomorphous substitution of the heteroatom in the framework. In this work, H-[Al/Ga/Fe]-ZSM-5 zeolites are synthesized with Si/T ratios = 80, 300, affecting the acid site strength as well as distribution of Brønsted and Lewis acid sites. On catalytic testing of the H-[Al/Ga/Fe]-ZSM-5/ZnO-ZrO2 samples for tandem CO2 hydrogenation and methanol conversion, the presence of weaker Brønsted acid sites improves the aromatics selectivity (CO2 to aromatics selectivity ranging from 13 to 47%); however, this effect of acid strength was not observed at low T atom content. Catalytic testing of H-[B]-ZSM-5/ZnO-ZrO2 provides no conversion of CO2 to hydrocarbons, showing that there is a minimum acid site strength needed for measurable aromatization reactivity. The H-[Fe]-ZSM-5-80/ZnO-ZrO2 catalyst shows the best catalytic activity with a CO2 conversion of ∼10% with a CO2 to aromatics selectivity of ∼51%. The catalyst is shown to provide stable activity and selectivity over more than 250 h on stream.

Utilizing Stems in Primary Total Knee Arthroplasty: Analysis of the Australian Orthopaedic Association National Joint Replacement Registry Data.

BACKGROUND: We compared revision rates and reasons for revision for primary total knee arthroplasty (TKA) performed for osteoarthritis with and without tibial stem extensions. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry were used to compare all-cause revision, reason, and type of revision between primary TKA using stemmed tibial prostheses and non-stemmed prostheses. RESULTS: All-cause revision for TKA with stem extension was higher for the first 6 months (hazard ratio [HR] 1.47; 95% confidence interval [CI]1.19 to 1.82; P < .001); while after 1.5 years TKA with stem extension had a lower rate of revision (HR 0.84; 95% CI 0.73 to 0.97; P = .01). Stemmed components were more likely to be revised for infection between 3 months and 1.5 years after surgery (HR 1.39; 95% CI 1.05 to 1.83; P = .02). The revision rate for aseptic loosening was lower in the stemmed group beyond 2 years (HR = 0.45; 95% CI 0.31 to 0.63; P < .001). Insert-only revision was higher in the stemmed group at all times (HR = 1.42; 95% CI 1.21 to 1.66, P < .001). Isolated tibial component revision was lower in the stemmed group at all times (HR 0.47; 95% CI 0.29 to 0.74; P = .001). Aseptic loosening for tibial component-only revision was significantly lower in the stemmed group at all times (HR 0.23; 95% CI 0.11 to 0.50; P < .001). CONCLUSIONS: Patients undergoing primary stemmed TKA have lower rates of all-cause revision beyond 1.5 years and tibial component-only revision at all times. Further investigation is required to preoperatively select patients that benefit from augmentation with stems.

The Clinical Frailty Scale is a Strong Predictor of 1-Year Mortality in Surgically Managed Hip Periprosthetic Fracture: An Analysis From a High-Volume Institution.

BACKGROUND: Hip periprosthetic fractures (PPFs) after primary total hip arthroplasty are increasing with the number of primary implants and aging population. Mortality has been reported up to 34% at 1-year. The aim of this study was to evaluate the association of Clinical Frailty Scale (CFS) and 1-year mortality, complication rate, and length of stay (LOS) in surgically managed hip PPFs. METHODS: This was a retrospective study of prospectively collected data from January 2008 to January 2021. A total of 282 surgically managed hip PPFs were identified. Mean age was 79 years (range, 42 to 106). Preoperative scores were analyzed through linear regression to identify significant association with mortality, complication and LOS. Receiver operating characteristic curve and Area Under the Curve (AUC) were generated to evaluate the quality of the models and the discriminatory ability of each clinical score. Significance was considered at P values < .05. RESULTS: Mortality was 7.8% at 3-months and 15.7% at 1-year. Complication rate requiring surgery was 19.5% and mean LOS was 8.9 ± 7 days. The CFS was significantly associated with 3-month (odds ratio 2.23, P < .001) and 1-year mortality (odds ratio 2.01, P < .001). The receiver operating characteristic curve test for 1-year mortality showed a greater AUC for the CFS when compared with American Society for Anesthesiologists score and age-adjusted Charlson Comorbidity Index (AUC 0.80 versus 0.68 versus 0.72, respectively). CONCLUSIONS: Frailty is a syndrome with increased risk of mortality after surgically managed PPF. The CFS can be easily assessed at the time of admission and could be considered as a strong and reliable predictor of 1-year mortality with a greater AUC than the conventionally used American Society for Anesthesiologists score.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Application of bone cement directly to the implant in primary total knee arthroplasty. Short-term radiological and clinical follow-up of two different cementing techniques.

PURPOSE: This study aimed to optimize cement application techniques in fully cemented primary total knee arthroplasty (TKA) by comparing the effects of two different approaches: cement on bone surface (CoB) versus cement on bone surface and implant surface (CoBaI) on the short-term presence of radiolucent lines (RLL) as indicators of potential complications. METHODS: In this monocentric study, a total of 379 fully cemented primary TKAs (318 patients) were included. The two study groups were differentiated by the technique of cement application: CoB group (cement applied only on bone surface) and CoBaI group (cement applied on both bone surface and implant surface). The presence of RLL or osteolysis was evaluated using the updated Knee Society Radiographic Evaluation System. RESULTS: In the whole study population, RLL were present in 4.7% of cases, with a significantly higher incidence in the CoBaI group (10.5%) at the 4-week follow-up. At the 12-month follow-up, RLL were observed in 29.8% of TKAs in the CoBaI group, while the incidence was lower in the CoB group (24.0%) (not statistically significant). There were two revisions in each group, none of which were due to aseptic loosening. CONCLUSION: The findings of this study suggest that the application of bone cement on bone surface only (CoB) may be more beneficial than applying it on both bone surface and implant surface (CoBaI) in terms of short-term presence of RLL in fully cemented primary TKA. Long-term results, especially with regard to aseptic loosening, will be of interest and may provide valuable guidance for future directions in bone cement applications in TKA.

Endoscopic Tendon Release for Iliopsoas Impingement After Total Hip Arthroplasty-Excellent Clinical Outcomes and Low Failure Rates at Short-Term Follow-Up.

PURPOSE: To investigate the clinical effectiveness of endoscopic iliopsoas tendon release (IPR) at the lesser trochanter (LT) in patients with iliopsoas impingement (IPI) after total hip arthroplasty (THA). METHODS: Between November 2017 and March 2021, a consecutive series of 36 patients were treated with endoscopic IPR for diagnosed IPI. Patients included had acetabular cup position confirmed by functional imaging (OPS, Corin, Pymble, NSW), typical clinical symptoms of IPI, and a positive response to diagnostic injection. Clinical assessment included validated patient-reported outcome measures (PROMs) along with hip flexion strength and active range of motion at different time marks up to 2-year follow-up, as well as surgical complications. RESULTS: Overall, 36 consecutive patients (11 males) with a mean age of 62 ± 12 years were included. All patients had failed nonoperative management. Dynamic computed tomography assessment was available in 89% of the patients, edge loading was reported in 10%, and variable cup overhang was reported in 50%. Clinically, PROMs were significantly improved at every time mark when compared with preoperative values (P < .001), showing the biggest improvement within the first 4 weeks after surgery. At the 6-month follow-up, peak isometric hip flexion strength on the operated side was 20% lower than the contralateral side (P < .001). Failure rate of the procedure was 2.8% (1 case). Linear regression showed no association between cup overhang and clinical outcomes. CONCLUSIONS: Endoscopic IPR at the LT is a safe and reproducible technique associated with significant and immediate improvement in pain, functional outcomes, and high patient satisfaction. With minimal short-term weakness, no complications, and only a single revision, even in cases with cup malposition and/or edge loading, we believe that endoscopic IPR can be considered as one of the first-line operative options in patients with symptomatic IPI, irrespective of component position. LEVEL OF EVIDENCE: Level IV, case series.

Stemmed Tibial Fixation for Primary Total Knee Arthroplasty in Obese Patients-A National Registry Study.

BACKGROUND: We investigated if the use of augmented tibial fixation with stems in primary total knee arthroplasty (TKA) in obese patients was associated with a difference in reason for revision, type of revision, or overall revision rate. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry compared reason for revision, rate, and type of revision between primary TKA using stemmed tibial prostheses to nonstemmed prostheses, stratified by body mass index (BMI) and obesity. The cumulative percent revision was obtained using the Kaplan-Meier method, and Cox proportional hazards models estimated hazard ratios (HRs) adjusted for age and sex with 95% confidence intervals (CIs). All tests were 2-tailed at 5% statistical significance (P < .05). There were 66,508 procedures available for analyses. RESULTS: Obese class 2 (BMI 35 to 39.99) had higher rates of revision in the stemmed group compared to the nonstemmed group (HR 1.44, 95% CI 1.00, 2.05, P = .047). There was no significant difference in revision rates between stemmed and nonstemmed tibial prostheses in any other BMI group. Primary TKA in obese patients (BMI ≥30) with a stem extension had a significantly higher rate of minor revisions compared to no stem extension (HR 1.31, 95% CI 1.03, 1.66, P = .025). There was no significant difference between stemmed and nonstemmed groups for major revision in obese patients and for minor or major revision in nonobese patients. CONCLUSION: Using a tibial stem during primary TKA in obese patients is not associated with a lower rate of revision.

What are the Outcomes of Secondary Patella Resurfacing for Dissatisfaction Following Primary Knee Arthroplasty? A Systematic Review and Meta-Analysis of 604 Knees.

BACKGROUND: Secondary patella resurfacing is often performed for dissatisfaction following primary knee arthroplasty where the native patella was retained. The purpose of this meta-analysis was to evaluate outcomes of secondary patella resurfacing. METHODS: The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting on patients who underwent secondary patella resurfacing after previous primary knee arthroplasty with retention of the native patella were considered eligible. The risk of bias was assessed using the Methodological Index for Non-Randomized studies tool. A random-effects model and the inverse-variance weighting method was used for meta-analysis. There were sixteen retrospective studies including 604 knees (594 patients) with a mean follow up of 42 months (range, 2 to 197). RESULTS: An overall improvement in patient-reported outcomes (PROMs) was achieved in 53% of cases from pooled data available for 293 knees [95% Confidence Interval (CI) (0.44, 0.62), I2=68% - moderate heterogeneity]. The pooled proportion of patients satisfied with the procedure was 59% [95% CI (48, 68), I2 = 70% - moderate heterogeneity] in a sample size of 415. There was a minimal rate (2%) of complication incidence when performing secondary patella resurfacing and a pooled rate of revision surgery of 10%. CONCLUSIONS: An improvement in pain, satisfaction, and PROMs was achieved in slightly more than half of the patients following secondary patella resurfacing. However, studies lacked standardized objective selection criteria for the procedure and the available data was predominantly retrospective, with high heterogeneity and variation in outcome reporting.

Cold Temperature Direct Air CO2 Capture with Amine-Loaded Metal-Organic Framework Monoliths.

Zeolites, silica-supported amines, and metal-organic frameworks (MOFs) have been demonstrated as promising adsorbents for direct air CO2 capture (DAC), but the shaping and structuring of these materials into sorbent modules for practical processes have been inadequately investigated compared to the extensive research on powder materials. Furthermore, there have been relatively few studies reporting the DAC performance of sorbent contactors under cold, subambient conditions (temperatures below 20 °C). In this work, we demonstrate the successful fabrication of adsorbent monoliths composed of cellulose acetate (CA) and adsorbent particles such as zeolite 13X and MOF MIL-101(Cr) by a 3D printing technique: solution-based additive manufacturing (SBAM). These monoliths feature interpenetrated macroporous polymeric frameworks in which microcrystals of zeolite 13X or MIL-101(Cr) are evenly distributed, highlighting the versatility of SBAM in fabricating monoliths containing sorbents with different particle sizes and density. Branched poly(ethylenimine) (PEI) is successfully loaded into the CA/MIL-101(Cr) monoliths to impart CO2 uptakes of 1.05 mmol gmonolith-1 at -20 °C and 400 ppm of CO2. Kinetic analysis shows that the CO2 sorption kinetics of PEI-loaded MIL-101(Cr) sorbents are not compromised in the monoliths compared to the powder sorbents. Importantly, these monoliths exhibit promising working capacities (0.95 mmol gmonolith-1) over 14 temperature swing cycles with a moderate regeneration temperature of 60 °C. Dynamic breakthrough experiments at 25 °C under dry conditions reveal a CO2 uptake capacity of 0.60 mmol gmonolith-1, which further increases to 1.05 and 1.43 mmol gmonolith-1 at -20 °C under dry and humid (70% relative humidity) conditions, respectively. Our work showcases the successful implementation of SBAM in making DAC sorbent monoliths with notable CO2 capture performance over a wide range of sorption temperatures, suggesting that SBAM can enable the preparation of efficient sorbent contactors in various form factors for other important chemical separations.

Long-term influence of sleep/wake history on the dynamic neurobehavioural response to sustained sleep restriction.

Chronic sleep restriction, common in today's 24/7 society, causes cumulative neurobehavioural impairment, but the dynamics of the build-up and dissipation of this impairment have not been fully elucidated. We addressed this knowledge gap in a laboratory study involving two, 5-day periods of sleep restriction to 4 hr per day, separated by a 1-day dose-response intervention sleep opportunity. We measured sleep physiological and waking neurobehavioural responses in 70 healthy adults, each randomized to one of seven dose-response intervention sleep doses ranging from 0 to 12 hr, or a non-sleep-restricted control group. As anticipated, sleep physiological markers showed homeostatic dynamics throughout the study, and waking neurobehavioural impairment accumulated across the two sleep restriction periods. Unexpectedly, there was only a slight and short-lived effect of the 1-day dose-response intervention sleep opportunity. Whether the dose-response intervention sleep opportunity involved extension, further restriction or total deprivation of sleep, neurobehavioural functioning during the subsequent second sleep restriction period was dominated by prior sleep-wake history. Our findings revealed a profound and enduring influence of long-term sleep-wake history as a fundamental aspect of the dynamic regulation of the neurobehavioural response to sleep loss.

Impact of Peptide Sequence on Functional siRNA Delivery and Gene Knockdown with Cyclic Amphipathic Peptide Delivery Agents.

Short-interfering RNA (siRNA) oligonucleotide therapeutics that modify gene expression by accessing RNA-interference (RNAi) pathways have great promise for the treatment of a range of disorders; however, their application in clinical settings has been limited by significant challenges in cellular delivery. Herein, we report a structure-function study using a series of modified cyclic amphipathic cell-penetrating peptides (CAPs) to determine the impact of peptide sequence on (1) siRNA-binding efficiency, (2) cellular delivery and knockdown efficiency, and (3) the endocytic uptake mechanism. Nine cyclic peptides of the general sequence Ac-C[XZ]4CG-NH2 in which X residues are hydrophobic/aromatic (Phe, Tyr, Trp, or Leu) and Z residues are charged/hydrophilic (Arg, Lys, Ser, or Glu) are assessed along with one acyclic peptide, Ac-(WR)4G-NH2. Cyclization is enforced by intramolecular disulfide bond formation between the flanking Cys residues. Binding analyses indicate that strong cationic character and the presence of aromatic residues that are competent to participate in CH-π interactions lead to CAP sequences that most effectively interact with siRNA. CAP-siRNA binding increases in the following order as a function of CAP hydrophobic/aromatic content: His < Phe < Tyr < Trp. Both cationic charge and disulfide-constrained cyclization of CAPs improve uptake of siRNA in vitro. Net neutral CAPs and an acyclic peptide demonstrate less-efficient siRNA translocation compared to the cyclic, cationic CAPs tested. All CAPs tested facilitated efficient siRNA target gene knockdown of at least 50% (as effective as a lipofectamine control), with the best CAPs enabling >80% knockdown. Significantly, gene knockdown efficiency does not strongly correlate with CAP-siRNA internalization efficiency but moderately correlates with CAP-siRNA-binding affinity. Finally, utilization of small-molecule inhibitors and targeted knockdown of essential endocytic pathway proteins indicate that most CAP-siRNA nanoparticles facilitate siRNA delivery through clathrin- and caveolin-mediated endocytosis. These results provide insight into the design principles for CAPs to facilitate siRNA delivery and the mechanisms by which these peptides translocate siRNA into cells. These studies also demonstrate the nature of the relationships between peptide-siRNA binding, cellular delivery of siRNA cargo, and functional gene knockdown. Strong correlations between these properties are not always observed, which illustrates the complexity in the design of optimal next-generation materials for oligonucleotide delivery.

Effects of Aircraft Noise on Sleep: Federal Aviation Administration National Sleep Study Protocol.

Aircraft noise can disrupt sleep and impair recuperation. The last U.S. investigation into the effects of aircraft noise on sleep dates back more than 20 years. Since then, traffic patterns and the noise levels produced by single aircraft have changed substantially. It is therefore important to acquire current data on sleep disturbance relative to varying degrees of aircraft noise exposure in the U.S. that can be used to check and potentially update the existing noise policy. This manuscript describes the design, procedures, and analytical approaches of the FAA's National Sleep Study. Seventy-seven U.S. airports with relevant nighttime air traffic from 39 states are included in the sampling frame. Based on simulation-based power calculations, the field study aims to recruit 400 participants from four noise strata and record an electrocardiogram (ECG), body movement, and sound pressure levels in the bedroom for five consecutive nights. The primary outcome of the study is an exposure-response function between the instantaneous, maximum A-weighted sound pressure levels (dBA) of individual aircraft measured in the bedroom and awakening probability inferred from changes in heart rate and body movement. Self-reported sleep disturbance due to aircraft noise is the secondary outcome that will be associated with long-term average noise exposure metrics such as the Day-Night Average Sound Level (DNL) and the Nighttime Equivalent Sound Level (Lnight). The effect of aircraft noise on several other physiological and self-report outcomes will also be investigated. This study will provide key insights into the effects of aircraft noise on objectively and subjectively assessed sleep disturbance.