Window Duration Research Articles

Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Novo Nordisk Foundation (Tandem Programme; #31634). Background Obstructive sleep apnea (OSA) creates a complex substrate for atrial fibrillation (AF), which is refractory to many clinically available pharmacological interventions. Purpose To investigate atrial antiarrhythmogenic properties and ventricular electrophysiological safety of small-conductance Ca2+ -activated K+ (SK)- channel inhibition in a porcine model for obstructive respiratory events. Methods In spontaneously breathing pigs, obstructive respiratory events were simulated by intermittent negative upper airway pressure (INAP) applied via a pressure device connected to the intubation tube. INAP was applied for 75 seconds, every 10 minutes, three times before and three times during infusion of the SK-channel inhibitor AP14145. Atrial effective refractory periods (AERP) were acquired before (Pre-INAP), during (INAP) and after (Post-) INAP. AF-inducibility was determined by a S1S2 atrial pacing protocol. For the purpose of drug safety, ventricular arrhythmicity was evaluated by heart rate adjusted QT-interval duration (QT-paced) and electromechanical window (EMW) calculation. Results During vehicle infusion, INAP transiently shortened AERP (Pre-INAP: 135±10 ms vs. Post-INAP 101±11 ms; p=0.008) and increased AF-inducibility. QT-paced prolonged during INAP (Pre-INAP 270±7 ms vs. INAP 275±7 ms; p=0.04) and EMW shortened progressively throughout INAP and Post-INAP (Pre-INAP 80±4 ms; INAP 59±6 ms, Post-INAP 46±10 ms). AP14145 prolonged baseline AERP, partially prevented INAP-induced AERP-shortening and reduced AF-susceptibility. AP14145 did neither alter QT-paced (Pre-AP14145 270±7 ms vs. AP14145 268±6 ms, p=0.83) nor INAP-induced QT-paced prolongation, but blunted Post-INAP associated EMW-shortening. Conclusion In a pig model for obstructive respiratory events, the SK-channel-inhibitor AP14145 prevented INAP-associated AERP-shortening and AF-susceptibility without impairing ventricular electrophysiology. Hence, SK-channels may represent a promising target for OSA-related AF.

Targeting river operations to the critical thermal window of fish incubation: Model and case study on Sacramento River winter‐run Chinook salmon

AbstractAllocating reservoir flows to meet societal and ecosystem needs under increasing water demands and climatic variability presents challenges to resource managers. Often, rivers have been regulated to meet flow and temperature compliance points or mimic historical patterns. Because it is difficult to assess if this approach is efficient, process‐based models are being used to design river operations. This paper describes a model for fish incubation survival based on the premise that mortality from thermal stress occurs over a critical window (CW) of embryo development. A model for the embryo CW based on metabolic studies of development is combined with density‐dependent and background mortalities to describe salmonid survival from egg fertilization to fry detection downstream. The model is calibrated with a two‐decade dataset of Sacramento River winter‐run Chinook salmon egg‐to‐fry survival. The effects of temperature exposure over a range of CWs were explored. Based on statistical and biological support, two alternative CWs were identified for temperature control: the entire incubation period and a short duration window prior to hatching. Survival under different CW assumptions and temperature control operations were simulated with an internet‐accessible form of the model. The analysis indicated that under years of limited cold‐water resources, targeting water releases to the CW prior to hatching would yield the highest incubation survival.

Relationship between QRS duration and resynchronization window for CRT optimization: Implications for CRT in narrow QRS patients

AimsCardiac resynchronization therapy (CRT) response is proportional to QRS duration (QRSd). We hypothesize that this is, in part, due to slower conduction velocity and hence wider range of programmed device settings that produce adequate electrical wavefront fusion and resynchronization in wider QRSd patients. MethodsCRT patients (n = 122) with left ventricular (LV) conduction delay, sinus rhythm and intact atrioventricular node conduction were studied. Patients were categorized by QRSd: narrow (<120 ms; n = 20); moderate (120–150 ms, n = 37); and prolonged (≥150 ms; n = 65). Electrocardiographic data was acquired during native rhythm and LV-only pacing at varying atrioventricular delays (AVDs). Electrical synchrony was quantified as cardiac resynchronization index (CRI) using multi‑lead electrocardiographic systems and a proprietary algorithm that quantified wavefront fusion. A Gaussian distribution equation was fitted to CRI response. ResultsPeak CRI was high (87.6 ± 6.3%) and similar (p = 0.716) across QRSd groups. The standard deviation of the Gaussian distribution significantly correlated with QRSd (R = 0.614, p < 0.001), and progressively and significantly (p < 0.001) increased as QRSd increased from narrow (34.8 ± 10.0 ms), to moderate (50.6 ± 8.4 ms), to prolonged (67.6 ± 18.3 ms). At AVDs 20 and 40 ms from optimal, CRI differed significantly (p < 0.001) between groups, with progressively higher CRI values as native QRSd increased. ConclusionElectrical resynchronization with optimally programmed LV-only pacing was similar between patients with varying QRSd, including patients with narrow QRSd. The resynchronization window that corresponded with optimal electrical resynchronization decreased as native QRSd decreased. This finding provides one potential explanation for the lack of significant benefit of CRT in narrow QRSd patients in previous studies.

Abstract MP58: Eating Behaviors Influence Diet Quality: Impact Of Sleep Restriction

Background: Eating behavior is an important construct with predictive value for energy intake and is associated with health. Two characteristics of eating behavior, eating window and eating frequency, are consistently associated with cardiometabolic risk across populations and have been shown to be related to sleep patterns. Both lifestyle factors have been related to cardiometabolic diseases but no long-term study has analyzed the association between sleep and eating behavior. Objective: To analyze the link between eating behavior and diet quality in a randomized, crossover study of sleep restriction (SR) vs adequate sleep (AS). Methods: Sixty-one participants (68% women, 20-73y) underwent 2 phases of 6 wk each, AS (sleep ≥7 h/night) and SR (-1.5 h/night relative to AS). Energy intake, diet quality, number of eating occasions (any eating/drinking episode providing at least 210kJ separated by &gt;15min) and eating window (time elapsed between the first and last eating occasion) were assessed at baseline, wk 3 and wk 6 of each phase using 3-d food records. Linear regression models were used to evaluate associations of eating behavior with diet quality by sleep condition, adjusting for confounding variables. Results: Participants had more eating occasions during SR compared to AS (β= 0.27±0.12, P=0.028). Duration of eating window also tended to be longer during SR compared to AS (β= 0.38±0.22, P=0.090). We then assessed the impact of these dietary behaviors on diet quality separately by condition. During AS, greater number of eating occasions was associated with greater energy intakes (β= 106.5±41.8, P=0.013), carbohydrates (β= 14.0±5.5, P=0.013), protein (β= 4.6±2.2, P=0.040), monounsaturated fat (β= 1.9±0.9, P=0.028), and fiber intakes (β= 2.1±0.8, P=0.010). Dietary glycemic index was also higher in those with greater eating occasions (β= 70.9±27.9, P=0.013). During SR, greater number of eating occasions was associated with greater energy intakes (β= 168.5±36.8, P&lt;0.001), fat (β= 6.3±2.1, P=0.004), carbohydrates (β= 19.7±4.7, P&lt;0.001), protein (β= 6.9±2.0, P&lt;0.001), saturated fat (β= 1.6±0.8, P=0.043), monounsaturated fat (β= 2.9±0.9, P=0.002), sugar (β= 6.5±1.8, P&lt;0.001), and fiber intakes (β= 2.2±0.7, P=0.003). Dietary glycemic index was also higher in those with greater eating occasions (β= 92.8±23.7, P&lt;0.001). Findings were similar but less pronounced for eating window duration. Conclusions: Higher eating frequency is associated with higher intakes of energy and several macronutrients. However, in the context of SR, more frequent eating occasions is associated with a worse dietary profile, namely greater intakes of saturated fat and sugar.

Abstract P208: The Impact Of Circadian Misalignment On Energy Metabolism And Substrate Oxidation In Adults With Adequate Sleep

Background: Circadian misalignment (CM), the mismatch between timing of behaviors and internal body clock, increases cardiometabolic risk, but the mechanisms are not fully understood. Population studies in night shift workers and intervention studies attempting to replicate CM have often been confounded by differences in energy intake, sleep duration and timing, and eating window duration. We aimed to investigate the effects of CM, induced by delaying mealtimes relative to wake time, independent of sleep timing and duration as well as duration of eating window, on energy expenditure (EE) and substrate oxidation. We hypothesized that CM would reduce EE and increase respiratory quotient (RQ) relative to meals closer to wake time (circadian alignment [CA]). Methods: We used a 2-phase, randomized, crossover study. Men and women (age 20-49 y) were studied under controlled feeding conditions (CA and CM). Each phase included a 10-h eating window at 0900-1900 h (CA) or 1300-2300 h (CM) with fixed mealtimes. Bedtimes were set at 2400-0800 h. Minute-by-minute EE, RQ, and substrate oxidation were obtained over 23 h in a metabolic chamber on d 3-4 and 14-15. Post-meal EE, RQ, and substrate oxidation were calculated as the average of 2-h, 1-h, and 30 min data collections following breakfast, dinner, and snack, respectively. Data were analyzed using a linear mixed effects model including condition, day, and day-by-condition interaction as main predictor variables, and phase as an adjusting covariate. As an exploratory aim, sex-by-condition interaction was also included in the model. Results: Three men and 4 women completed both study phases (age 37.6±8.8 y, BMI 30.8±3.2 kg/m 2 ). EE did not differ between CM and CA. Post-meal RQ for breakfast (p=0.06), dinner (p&lt;0.001), and snack (p&lt;0.001) were higher in CM vs CA. Glucose oxidation after dinner (p&lt;0.001) and snack (p&lt;0.01) were higher in CM vs CA. There were sex-by-condition interactions on EE and glucose oxidation after breakfast (both p=0.06) and dinner (p&lt;0.05), and on EE after snack (p&lt;0.01). In general, CA resulted in greater rise in EE and lesser reduction in glucose oxidation following meals in men compared to women. Conclusion: Delaying mealtimes by 4 h, independent of sleep duration, timing, or diet composition, shifts nutrient metabolism towards greater carbohydrate and lower fat oxidation. Sex may influence the effect of CM on energy metabolism and should be considered in investigations of cardiometabolic risk associated with shift work and late-night eating.

On the automatic detection of enacted compulsive hand washing using commercially available wearable devices

BackgroundCompulsive hand washing is one of the most frequent compulsions and includes highly ritualized, repetitive hand motions. Developing an algorithm that can automatically detect compulsive washing with off-the-shelf wearable devices is a first step toward developing more sophisticated sensor-based assessments and micro-interventions that might ultimately supplement cognitive behavioral therapy for obsessive-compulsive disorder (OCD). ObjectiveThe main objective was to establish whether enacted compulsive hand washing can be distinguished from routine hand washing. This distinction will inform future research on the development of an algorithm that can automatically detect compulsive hand washing. MethodTwenty-one participants were trained individually to wash their hands according to 1 of 5 scripted hand-washing procedures that were based on descriptions of pathological compulsive washes and additionally to wash their hands as they usually would, while wearing a smartwatch. Washes were video recorded to obtain validation data. To generate a baseline model, we opted to extract well-known features only (mean and variance of each sensor axis). We tested four classification models: linear support vector machine (SVM), SVM with radial basis functions, random forest (RF), and naive Bayes (NB). Leave-one-subject-out cross-validation was applied to gather F1, specificity, and sensitivity scores. ResultsThe best-performing parameters were a classification window duration of 10 s, with a mean-variance feature set calculated from quaternions, rate of turn, and magnetic flux measurements. The detection performance varied with the particular enacted compulsive hand wash (F1 range: 0.65–0.87). Overall, enacted compulsive and routine hand washing could be distinguished with an F1 score of 79% (user independent), a sensitivity of 84%, and a specificity of 30%. ConclusionsOur analysis of the sensor data demonstrates that enacted compulsive hand washing could be distinguished from routine hand washing with acceptable sensitivity. However, specificity was low. This study is a starting point for a series of follow-ups, including the application in individuals diagnosed with OCD.

Effects of feeding duration, implant dose, and terminal window duration on growth performance and carcass characteristics of feedyard steers and heifers

Our objective was to evaluate effects of feeding duration (days on feed, DOF), terminal window (TW), and implant program dose on growth performance and carcass characteristics of beef steers and heifers. Heifers in Exp. 1 (n = 3,360; 351 ± 31 kg) and Exp. 2 (n = 3,778; 310 ± 28 kg) were used in randomized complete block designs with 3 × 2 factorial treatment arrangements. In Exp. 1, factor 1 was DOF (139, 162, and 183) and factor 2 was TW (60 or 100). In Exp. 2, factor 1 was implant program {(1) IH/H—Component TE-IH with Tylan on d 0 followed by a Component TE-H with Tylan [140 mg of trenbolone acetate (TBA):14 mg of estradiol; Elanco], (2) IH/200—Component TE-IH with Tylan on d 0 followed by a Component TE-200 with Tylan, and (3) 200/200—Component TE-200 with Tylan on d 0 and at reimplant} and factor 2 was TW (60 or 100). In Exp. 3, feedlot data from an industry database (Benchmark, Elanco Knowledge Solutions, Kansas City, KS) was used in an observational study and organized by sex and implant program [steers = IS/200 (total of 280 mg of TBA and 36 mg of estradiol), XS (200 mg of TBA and 40 mg of estradiol), and 200/200 (a total dose of 400 mg of TBA and 40 to 56 mg of estradiol or estradiol benzoate); heifers = IH/200 (total of 280 mg of TBA and 28 mg of estradiol) and 200/200]. Repeated-measure and nonlinear broken-slope models were used to evaluate TW on live performance. In Exp. 1, ADG decreased ( P = 0.03) and final BW, marbling score, hot carcass weight (HCW), backfat thickness, and calculated empty body fat (EBF) increased ( P < 0.03) as DOF increased. In Exp. 2, greater implant program dose tended ( P ≤ 0.10) to increase ADG and DMI and increase ( P ≤ 0.02) G:F, HCW, DP, and LM area. Furthermore, overall dose reduced ( P ≤ 0.03) marbling score and EBF. In Exp. 3, interactions between implant program, live performance, and TW were detected ( P < 0.001). Steers given 200/200 exhibited the greatest ( P < 0.05) ADG, followed by XS and IS/200 from TW 50 to 100. Inversely, steers given XS had the greatest ( P < 0.05) F:G, followed by IS/200 and 200/200 from TW 50 to 90. Heifers administered 200/200 exhibited greater ( P < 0.05) ADG between TW 50 to 70 and reduced ( P < 0.05) F:G through TW 110 compared with IH/200. Increased DOF resulted in reduced ADG and increased HCW and EBF. Increased implant dose improved live performance and HCW. There is a finite number of TW days before growth suffers from inadequate stimuli. Furthermore, cattle type, implant program dose, DOF, and TW all require consideration when designing implant programs.

A single-center pilot study comparing dexmedetomidine continuous infusion versus propofol TCI for drug-induced sleep endoscopy (DISE)

Background: Drug-induced sleep endoscopy (DISE) has become a routine diagnostic tool to assess the upper airway in obstructive sleep apnea patients, enabling effective diagnosis and appropriate treatment of the obstruction site. A number of protocols with different drugs and availability of target-controlled infusion (TCI) systems have been reported and published, making comparisons between studies difficult. In recent years, dexmedetomidine has claimed a role as a potential alternative to propofol for DISE sedation. In a real-life study we compared the effects of dexmedetomidine continuous infusion or propofol-TCI in patients undergoing DISE on time to reach adequate observation conditions, cardio-respiratory parameters, and recovery. Methods: Pilot prospective, randomized not blinded, single center study. A total of 28 patients scheduled to have DISE were randomly assigned to either group P (N=14; propofol-TCI, initial propofol effect-site target concentration 2.0 µg/mL, increased by 0.3 µg/mL every 2 min) or group D (N=14; dexmedetomidine bolus 1 µg/kg over 10 min, followed by infusion at 0.7 µg/kg/h). Hemodynamic and respiratory variables (including SpO2 nadir), time to reach the observation window and overall DISE duration were recorded. Results: A total of 28 patients were enrolled and completed the study: the cohort included 26 males (92.85%) and 2 females (7.14%). The mean age was 45.4±11.1 years [interquartile (IQ), 25.0–65.0], body mass index 30.5±3.4 kg/m2 (IQ, 21.0–36.0), and apnea-hypopnea index 36.9±21.1 events/hour (IQ, 7.8–95.0). There were no statistically significant differences between the 2 groups in baseline apnea-hypopnea index, oxygen desaturation index, Epworth Sleepiness Scale score, preprocedural SpO2 nadir, age, sex, or body mass index. Compared with group P, group D showed significant differences in SpO2 (higher nadir during DISE, 87.09±5.4% vs. 75.0±11.0; P&lt;0.001) and heart rate (80.4±8.9 vs. 62.8±6.6; P&lt;0.001). While group D had longer duration of endoscopic examination times and emergence time from sedation, the grading of site of obstructions were similar in the 2 groups. Conclusions: Dexmedetomidine seems a limited, if viable, clinical alternative for DISE when propofol is contraindicated or not available: while causing higher SpO2 nadirs compared with propofol, it has a slow onset and longer recovery time, increasing total procedural time. Studies with greater patient numbers are needed to confirm these observations.

Effect of climate variability on water quality trends in New Zealand rivers

Associations between temporal variability in 10 water quality variables and the El Niño–Southern Oscillation (ENSO) climate pattern, quantified by the Southern Oscillation Index (SOI), were assessed at 56 river sites in New Zealand over a 31-year period (1989–2019). Fluctuations in monthly observations of water quality at each site were correlated to varying degrees with the corresponding SOI value (ro). Trends for rolling windows of 5-, 10- and 15-year duration were evaluated for each site and variable using Kendall’s tau (τw) and for the SOI using linear regression (δSOIw). Aggregate trends for each variable, duration and time window were quantified as proportions of site trends that were increasing (Pw). Fluctuations in τw and Pw between time windows for all durations were explained by the corresponding SOI trend (δSOIw). Between-site and between-variable differences in the trend responses to the SOI trends were explained by the corresponding ro values and the median of the ro values (MF21087_IE1.gif) respectively. These results indicate that climate variability makes a significant contribution to water quality trends, even at timescales longer than ENSO cycles. Our models can be used to quantify this contribution for individual sites (i.e. τw) and for aggregate trends (i.e. Pw).

Criterion Validity of an Automated Method of Detecting Live Play Periods in Basketball.

This study aimed to develop an automated method to detect live play periods from accelerometry-derived relative exercise intensity in basketball, and to assess the criterion validity of this method. Relative exercise intensity (% oxygen uptake reserve) was quantified for two men's semi-professional basketball matches. Live play period durations were automatically determined using a moving average sample window and relative exercise intensity threshold, and manually determined using annotation of video footage. The sample window duration and intensity threshold were optimised to determine the input parameters for the automated method that would result in the most similarity to the manual method. These input parameters were used to compare the automated and manual active play period durations in another men's semi-professional match and a women's professional match to assess the criterion validity of the automated method. The optimal input parameters were a 9-s sample window and relative exercise intensity threshold of 31% oxygen uptake reserve. The automated method showed good relative (ρ = 0.95–0.96 and ICC = 0.96–0.98, p < 0.01) and absolute (median bias = 0 s) agreement with the manual method. These findings support the use of an automated method using accelerometry-derived relative exercise intensity and a moving average sample window to detect live play periods in basketball.

A Novel Procedure of Enhancing the Throughput of a Mode-2 Sidelink Based on Partial Sensing.

Partial sensing is used to reduce the power consumption of pedestrian user equipment (P-UE) that operates in the signal environment of a mode-2 sidelink. However, because the data trans-mission is allowed only for the window duration of each corresponding P-UE, the throughput of the P-UE decreases by the ratio between the width of the window and the entire data period. This paper presents a novel method for enhancing the throughput of the P-UE that operates with partial sensing in the mode-2 sidelink. The proposed technique employs an additional UE, denoted the roadside unit (RSU), to collect the sensing results from each P-UE that operates with partial sensing. The proposed RSU sequentially aligns all of the partial sensing windows, such that the combination of each partial sensing window can eventually provide an almost complete sensing result. In this study, extensive computer simulations were performed. The results reveal that the proposed method enhances the throughput of each P-UE operating with partial sensing almost to that of full sensing without increasing the required power consumption.

Abstract 1337: Functional genomic characterization of the USP1 inhibitor KSQ-4279 reveals a distinct mechanism of action and resistance profile relative to other DDR targeting drugs

Abstract Genomic instability is a hallmark of most cancers that enables tumor cells to adapt and evolve, but also creates vulnerabilities that can be therapeutically exploited. Cancer therapies that target the DNA Damage Response (DDR) have proven to be efficacious across a broad range of cancer types, but often present a narrow therapeutic window and limited duration of response due to the development of resistance. Through mining our proprietary CRISPRomics® Oncology dataset we identified the ubiquitin protease, USP1, as an attractive target with activity in ovarian and triple negative breast cancers (TNBC). USP1 facilitates DNA repair via its role regulating the Fanconi anemia complex and translesion synthesis. We developed a series of potent, selective USP1 inhibitors to investigate the therapeutic potential of targeting USP1 in tumor settings dependent on those DNA repair processes. When profiled across a broad range of cancer cell line models, the USP1-inhibitor KSQ-4279 showed anti-proliferative effects in a subset of cell lines, often characterized by the presence of homologous recombination deficiencies (HRD), including mutations in BRCA1/2. To better understand the mechanism of action of KSQ-4279, we employed large scale functional genomic screens using KSQ-4279, olaparib, and cisplatin, in combination with a DNA-repair focused CRISPR library, to identify genetic determinants of sensitivity and anticipate modes of drug resistance. In addition to recovering genetic associations between KSQ-4279 and genes that modify USP1's direct substrates, our screens identified genetic interactions of KSQ-4279 with multiple DNA repair pathways, including genes involved in ubiquitin-mediated signaling events that regulate the response to DNA damage and replication stress. These studies revealed that the profile of resistance to KSQ-4279 is distinct from, and in some cases complementary to, other DNA damaging agents, and provide a mechanistic rationale for the use of KSQ-4279 in combination with other agents that target DNA repair. Consistent with the largely non-overlapping resistance profile of USP1 and PARP inhibitors, we found that the combination of KSQ-4279 with olaparib was able to induce strong and durable regressions across a number of ovarian and TNBC PDX models. Citation Format: Sol Shenker, Hugh Gannon, Alyssa Carlson, Paula Grasberger, Pamela Sullivan, Chris Middleton, Anne Dodson, Caroline Bullock, Michael McGuire, Erica Tobin, Kerstin Sinkevicius, Mike Schlabach, Frank Stegmeier, Louise Cadzow, Andrew Wylie. Functional genomic characterization of the USP1 inhibitor KSQ-4279 reveals a distinct mechanism of action and resistance profile relative to other DDR targeting drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1337.

Quantifying and modelling the game speed outputs of English Championship soccer players

ABSTRACT This study aims to quantify and model the game-speed demands of professional soccer players competing in the English Championship league, to compare the effect of match location and to examine the effect of playing position on game-speed outputs across the season. Twenty-eight male professional soccer players were enrolled. Moving average calculations were applied to the raw GNSS (STATSports) speed data of each player’s duration matches (home = 14 and away = 9). Positional groups were centre-back (CB), full-back (FB), centre-midfield (CM), wing-midfield (WM) and centre-forward (CF). The maximum value across each of the moving average window durations was extracted and converted to units of metres per minute. Power-law models were fitted to all observations (R2 = 0.64), home only (R2 = 0.98), and away only (R2 = 0.98). No significant effects are observed in game-speed outputs when home and away games are analysed. Significant differences were seen between the following positional groups; CBvs.CF (d = −0.323), CM (d = −0.530) and FB (d = −0.350). CM displayed positive difference compared to WM (d = 0.614). This study reported power-law model fitted game speed. Players’ positional groups have significantly different game-speed demands, which should be considered during match analysis and training periodization. This study found that game speed is not affected by the location of the match.

A two-stage hybrid heuristic solution for the container drayage problem with trailer reposition

Container drayage operations with tractor-trailer distinction and trailer reposition exist widely in real-world logistics yet have seldom been reported in the literature. This paper studies a container drayage problem with trailer reposition (CDPTR), in which trailers might be provided at pickup locations and kept at delivery locations. A two-stage solution framework is adopted to solve the problem. The first stage generates tractor schedules to maximize profit, and the second stage aims to ensure sufficient trailers at each trailer depot during the container drayage operation. A hybrid large neighborhood search and tabu search (LNS-TS) heuristic is developed to solve the problem. We construct 72 instances with different characteristics, for example, time window duration, initial trailer resource and distribution, and the number of requests. Results show that our solutions outperform the solutions obtained from the solver. A detailed analysis of the results also reveals several insights for container drayage operators.

Dynamic theta/beta ratio of clinical EEG in Alzheimer's disease

BackgroundEEG of a resting state in Alzheimer disease (AD) patients and healthy controls (HC) are analyzed to identify the characteristics of EEG in AD. New methodA dynamic box plot approach to the theta/beta ratio with various window durations is proposed to analyze EEG. ResultsSpectral results during a resting state in AD patients demonstrate the effect of relatively greater power in the low-frequency bands (i.e. ‘slowing down’ of the EEG). A significant difference is observed in the dynamic distribution of the theta/beta ratio in the AD and HC groups, which is related to the effect of ‘slowing down’. There is a more obvious visual separation between the theta/beta ratio results for the AD and HC groups with increasing window durations. Variability of the theta/beta ratio can be observed with shorter window durations with a dynamic functional box plot. This provides a better classification accuracy by using the dynamic theta/beta ratio as a sensor to discriminate AD EEG from HC EEG by using the receiver operating characteristics (ROC) curve and the area under curve (AUC) with various window durations. Comparison with existing method(s)EEG spectral analysis and theta/beta ratio used to evaluate EEG typically rely on long time averaging. ConclusionsThe dynamic box plot approach to the theta/beta ratio with various window durations provides the possibility of observing features of the EEG. The dynamic theta/beta ratio is a better sensor to discriminate AD EEG from HC EEG. Moreover, the reliability and accuracy of results can be increased by combining spectral analysis and the dynamic box plot approach to theta/beta ratio with various window durations.

359 Tailoring of Cognitive Behavior Therapy for Insomnia for Patients with Kidney Failure Undergoing Hemodialysis: The SLEEP-HD Study

Abstract Introduction Patients with kidney failure treated with hemodialysis (HD) frequently report insomnia symptoms. Cognitive-behavior therapy for insomnia (CBT-I) is a first line treatment for insomnia but there are unique issues surrounding kidney failure and HD that impact patients’ ability to access CBT-I and follow standard treatment recommendations. This presentation describes CBT-I protocol modifications made to address these issues as part of an ongoing multi-center clinical trial testing the efficacy of telehealth CBT-I compared to trazodone or medication placebo control. Methods CBT-I protocol modifications were made prior to starting the SLEEP-HD randomized trial based upon unique clinical considerations for HD patients, e.g., irregular sleep-wake scheduling that HD treatment demands, and napping during HD sessions or afterwards due to post-HD treatment fatigue. Participants in the SLEEP-HD study are undergoing thrice-weekly maintenance hemodialysis for &amp;gt;3 months and have baseline Insomnia Severity Index scores &amp;gt;10 with sleep disturbances &amp;gt;3 nights/week for &amp;gt;3 months. Participants randomized into the modified CBT-I protocol receive six weekly sessions, delivered by trained CBT-I therapists (1 MSW, 1 PhD) face-to-face via a HIPPA-compliant video telehealth platform. Participants keep a daily sleep diary throughout the CBT-I treatment period. Results To date, 91 patients (mean age=56.5 years [SD=14.7], 48.4% female) recruited from community-based dialysis facilities in Seattle and Albuquerque have been randomized into the SLEEP-HD study (n=31 CBT-I). Forty-eight percent of CBT-I clients have chosen to conduct their telehealth sessions during dialysis with the remainder choosing a different location. CBT-I adaptations include therapists developing weekly bed restriction recommendations based on non-dialysis treatment days; allowing shifts in dialysis day “bed window” scheduling for patients with very early or very late dialysis schedules so long as a consistent total time in bed in maintained; and including napping during early/late dialysis sessions as part of the allowable bed window duration. Treatment modifications were also designed to accommodate the diverse socioeconomic circumstances of dialysis patients, including housing instability, which can impact adherence to some standard stimulus control and bed restriction CBT-I recommendations. Conclusion It is feasible to deliver CBT-I via telehealth to HD patients but modifications to standard protocols are required. Support (if any) This work was supported by PHS grant 5R01AG053221.

Analysis of correlation between window duration for kurtosis computation and accuracy of noise-induced hearing loss prediction.

Kurtosis is considered an important metric for evaluating noise-induced hearing loss (NIHL). However, how to select window duration to calculate kurtosis remains unsolved. In this study, two algorithms were designed to investigate the correlation between window duration for kurtosis computation and the accuracy of NIHL prediction using a Chinese industrial database. Pure-tone hearing threshold levels (HTLs) and full-shift noise were recorded from each subject. In the statistical comparison, subjects were divided into high- and low-kurtosis groups based on kurtosis values computed over different window durations. Mann-Whitney U test was used to compare the difference in group HTLs to find the optimal window duration to best distinguish these two groups. In the support vector machine NIHL prediction model, kurtosis obtained from different window durations was used as a feature of the model for NIHL evaluation. The area under the curve was used to evaluate the performances of models. Fourteen window durations were tested for each algorithm. Results showed that 60 s was an optimal window duration that allows for both efficient computation and high accuracy for NIHL evaluation at test frequencies of 3, 4 and 6 kHz, and the geometric mean of kurtosis sequence was the best metric in NIHL evaluation.

Position specific peak impact and running demands of professional rugby union players during game play

This study quantifies the maximum number of impacts and peak running demands during 1– to 10– minute rolling window periods in elite rugby union matches using a multi-team dataset (n = 2232 player-games). Maximum values for impacts (impacts·min−1) and running (m·min−1) were calculated for 161 athletes from four teams across the 2018 and 2019 Super Rugby seasons. The effect of window duration and playing position on peak impact and running demands were estimated using linear mixed effect models and prediction intervals. The peak impact and running demands for a 1-min period were 4.5 – 5.5 impacts·min−1 and 150 – 180 m·min−1, depending on playing position. While small variations in mean impact and running movements could be observed by position, the large prediction interval and individual player variation meant that there was no practically meaningful difference by position. As such, when prescribing training drills to replicate the peak demands in rugby union, impact and running movements of players can be similar, regardless of position. Using a prediction interval allows us to identify the range where the demands in a future game may fall, and are beneficial to use when also trying to prepare players for the demands of rugby union.

Real-world emissions from modern heavy-duty vehicles: Sensitivity analysis of in-use emissions analysis methods

This study presents an analysis of real-world emissions from two heavy-duty trucks using the Not-To-Exceed (NTE) and the European based Work-Based-Window (WBW) methodologies. The study also presents a sensitivity analysis of the NTE and WBW approach to key parameters such as window duration, torque, power, and exhaust aftertreatment thresholds. The analysis is performed on data collected from two heavy-duty diesel vehicles operated under real-world conditions in California over various routes that include a combination of urban and freeway type operation. The results presented show that only 10–30% of the total data meets the required exclusion criteria prescribed by the current NTE regulation. Reducing the NTE window duration from the existing 30 to 10 s increases the number of windows available to perform NTE analysis. The study also shows that exempting data that correspond to exhaust aftertreatment system (EATS) temperature threshold of below 250 °C is the most dominant parameter influencing the number of available windows in an urban-type operation. The WBW approach produces a rich collection of data points that are representative of the in-use emissions characteristic of the vehicle. The results of NOx vs CO2 using a 4-quadrant analysis from the WBW approach is indicative of a difference in engine manufacturer design and emissions control strategy pertaining to real-world operation. The results of the study show that revisions to the boundaries and exclusions to the NTE zone would contribute to broadening the scope of in-use assessment of heavy-duty vehicle operation. However, even with such modifications, the NTE may not apply to highly transient urban vocations such as delivery, refuse and transit bus vocations. While comparing the moving average WBW approach to the NTE, the former approach produces a significantly larger number of data points for in-use assessment.

Association between Time Restricted Feeding and Cognitive Status in Older Italian Adults.

Background: Due to the increased life expectancy, the prevalence of aging-related health conditions, such as cognitive impairment, dementia and Alzheimer’s disease is increasing. Among the modifiable risk factors, dietary factors have proved to be of primary importance in preserving and improving mental health and cognitive status in older adults, possibly through the modulation of adult neurogenesis, neuronal plasticity and brain signaling. Feeding/fasting timing manipulation has emerged as an innovative strategy to counteract and treat cognitive decline. The aim of this study was to investigate the association between the timing of the feeding period and cognitive status in a cross-sectional cohort of adults living in the Mediterranean area. Methods: Demographic and dietary characteristics of 883 adults living in Southern Italy (Sicily) were analyzed. Food frequency questionnaires were used to calculate the time window between the first and the last meal of an average day. Participants with an eating time window duration of more than 10 h were then identified, as well as those with eating time restricted to less than 10 h (TRF). Results: After adjusting for potential confounding factors, individuals adherent to TRF were less likely to have cognitive impairment, compared to those with no eating time restrictions [odds ratio (OR) = 0.28; 95% confidence intervals (CI): 0.07–0.90]; a similar association was found for individuals having breakfast (OR = 0.37, 95% CI: 0.16–0.89), but not for those having dinner. Conclusions: The results of this study reveal that time restricted eating may be positively associated with cognitive status, and thus exert plausible effects on brain health.