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Abstract Background cis-Regulatory modules (CRMs) of eukaryotic genes often contain multiple binding sites for transcription factors. The phenomenon that binding sites form clusters in CRMs is exploited in many algorithms to locate CRMs in a genome. This gives rise to the problem of calculating the statistical significance of the event that multiple sites, recognized by different factors, would be found simultaneously in a text of a fixed length. The main difficulty comes from overlapping occurrences of motifs. So far, no tools have been developed allowing the computation of p-values for simultaneous occurrences of different motifs which can overlap. Results We developed and implemented an algorithm computing the p-value that s different motifs occur respectively k1, ..., ks or more times, possibly overlapping, in a random text. Motifs can be represented with a majority of popular motif models, but in all cases, without indels. Zero or first order Markov chains can be adopted as a model for the random text. The computational tool was tested on the set of cis-regulatory modules involved in D. melanogaster early development, for which there exists an annotation of binding sites for transcription factors. Our test allowed us to correctly identify transcription factors cooperatively/competitively binding to DNA. Method The algorithm that precisely computes the probability of simultaneous motif occurrences is inspired by the Aho-Corasick automaton and employs a prefix tree together with a transition function. The algorithm runs with the O(n|Σ|(m|ℋ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaat0uy0HwzTfgDPnwy1egaryqtHrhAL1wy0L2yHvdaiqaacqWFlecsaaa@3762@| + K|σ|K) ∏i ki) time complexity, where n is the length of the text, |Σ| is the alphabet size, m is the maximal motif length, |ℋ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaat0uy0HwzTfgDPnwy1egaryqtHrhAL1wy0L2yHvdaiqaacqWFlecsaaa@3762@| is the total number of words in motifs, K is the order of Markov model, and ki is the number of occurrences of the ith motif. Conclusion The primary objective of the program is to assess the likelihood that a given DNA segment is CRM regulated with a known set of regulatory factors. In addition, the program can also be used to select the appropriate threshold for PWM scanning. Another application is assessing similarity of different motifs. Availability Project web page, stand-alone version and documentation can be found at http://bioinform.genetika.ru/AhoPro/

Purpose: Optimal ankle dorsiflexion range of motion plays a vital role in attaining the essential crouched posture necessary for excelling in speed skating. The purpose of this study was to determine how the ankle dorsiflexion angle evolves throughout a day of training and to identify the factors that influence this angle. Methods: Thirty short-track speed skaters, from 2 teams, participated in this study. The maximum ankle dorsiflexion angle was obtained in a lunge position facing a wall, using a digital inclinometer. All measures were obtained 3 times per side, 6 times per day, on 2 training days separated by at least a week. We conducted multiple tests to study the impact of repetition, day, side, team level, sex, and moment on the ankle dorsiflexion angle. Results: The 3 times repeated measures and the 2 days of training did not have a significant influence on the results. There was a statistically significant difference between the first time point of the day and the 5 other time points for both ankles. Moreover, the influence of sex and team level was not statistically significant. Conclusions: The results indicate that there are significant changes in ankle dorsiflexion range of motion but only after the first warm-up of the day. Such findings could enable team staff to enhance athletes' precompetition preparation and tailor ankle mobility training regimens more effectively. [ABSTRACT FROM AUTHOR]

In this paper, we propose a new algorithm for solving convex-concave saddle-point problems using regret minimization in the repeated game framework. To do so, we introduce the Conic Blackwell Algorithm+ (CBA+), a new parameter- and scale-free regret minimizer for general convex compact sets. CBA+ is based on Blackwell approachability and attains O(T) regret. We show how to efficiently instantiate CBA+ for many decision sets of interest, including the simplex, ℓp norm balls, and ellipsoidal confidence regions in the simplex. Based on CBA+ , we introduce SP-CBA+ , a new parameter-free algorithm for solving convex-concave saddle-point problems achieving a O(1/T) ergodic convergence rate. In our simulations, we demonstrate the wide applicability of SP-CBA+ on several standard saddle-point problems from the optimization and operations research literature, including matrix games, extensive-form games, distributionally robust logistic regression, and Markov decision processes. In each setting, SP-CBA+ achieves state-of-the-art numerical performance and outperforms classical methods, without the need for any choice of step sizes or other algorithmic parameters. Funding: J. Grand-Clément is supported by the Agence Nationale de la Recherche [Grant 11-LABX-0047] and by Hi! Paris. C. Kroer is supported by the Office of Naval Research [Grant N00014-22-1-2530] and by the National Science Foundation [Grant IIS-2147361]. [ABSTRACT FROM AUTHOR]

The article focuses on evaluating the effectiveness of a provincial prehospital trauma triage protocol (EQTPT) in identifying patients needing urgent trauma care, assessing its sensitivity and specificity in a regional context. Topics include the protocol's performance in distinguishing between different levels of trauma severity based on patient outcomes and the implications for improving prehospital triage practices to enhance timely.

Biomechanics and training load monitoring are important for performance evaluation and injury prevention in elite swimming. Monitoring of performance and swim stroke parameters is possible with inertial measurement units (IMU) but has not been validated in para-swimmers. The purpose of this study was to validate a single IMU-based system to accurately estimate pool-swam lap time, stroke count (SC), stroke duration, instantaneous stroke rate (ISR), and distance per stroke (DPS). Eight Paralympic athletes completed 4 × 50 m swims with an IMU worn on the sacrum. Strokes cycles were identified using a zero-crossing algorithm on the medio-lateral (freestyle and backstroke) or forward-backward (butterfly and breaststroke) instantaneous velocity data. Video-derived metrics were estimated using Dartfish and Kinovea. Agreement analyses, including Bland–Altman and Intraclass Correlation Coefficient (ICC), were performed on all outcome variables. SC Bland–Altman bias was 0.13 strokes, and ICC was 0.97. ISR Bland–Altman biases were within 1.5 strokes/min, and ICCs ranged from 0.26 to 0.96. DPS Bland–Altman biases were within 0.20 m, and ICCs ranged from 0.39 to 0.93. A single-IMU system can provide highly valid performance and swim stroke monitoring data for elite para-swimmers for the majority of strokes, with the exception of backstroke. Future work should improve bilateral stroke detection algorithms in this population. [ABSTRACT FROM AUTHOR]

Patients whose transfer to the intensive care unit (ICU) is unplanned are prone to higher mortality rates. In "Robustness of Proactive Intensive Care Unit Transfer Policies," the authors study the problem of finding robust patient transfer policies to the ICU, which account for uncertainty in statistical estimates because of data limitations when optimizing to improve overall patient care. Under general assumptions, it is shown that an optimal transfer policy has a threshold structure. A robust policy also has a threshold structure, and it is more aggressive in transferring patients than the optimal nominal policy, which does not consider parameter uncertainty. The sensitivity of various hospital metrics to small changes in the parameters is highlighted using a data set of close to 300,000 hospitalizations at 21 Kaiser Permanente Northern California hospitals. This work provides useful insights into the impact of parameter uncertainty on deriving simple policies for proactive ICU transfer that have strong empirical performance and theoretical guarantees. Patients whose transfer to the intensive care unit (ICU) is unplanned are prone to higher mortality rates and longer length of stay. Recent advances in machine learning to predict patient deterioration have introduced the possibility of proactive transfer from the ward to the ICU. In this work, we study the problem of finding robust patient transfer policies that account for the important problem of uncertainty in statistical estimates because of data limitations when optimizing to improve overall patient care. We propose a Markov decision process model to capture the evolution of patient health, where the states represent a measure of patient severity. Under fairly general assumptions, we show that an optimal transfer policy has a threshold structure (i.e., that it transfers all patients above a certain severity level to the ICU (subject to available capacity)). As model parameters are typically determined based on statistical estimations from real-world data, they are inherently subject to misspecification and estimation errors. This is an important issue, which can lead to choosing significantly suboptimal policies. We account for this parameter uncertainty by deriving a robust policy that optimizes the worst-case reward across all plausible values of the model parameters. We are able to show that the robust policy also has a threshold structure under fairly general assumptions and that it is more aggressive in transferring patients than the optimal nominal policy, which does not take into account parameter uncertainty. We present computational experiments using a data set of hospitalizations at 21 Kaiser Permanente Northern California hospitals and present empirical evidence of the sensitivity of various hospital metrics (mortality, length of stay, and average ICU occupancy) to small changes in the parameters. Although threshold policies are a simplification of the actual complex sequence of decisions leading (or not) to a transfer to the ICU, our work provides useful insights into the impact of parameter uncertainty on deriving simple policies for proactive ICU transfer that have strong empirical performance and theoretical guarantees. Funding: J. Grand-Clément is a Hi! Paris chair holder and is supported by the Agence Nationale de la Recherche [Grant ANR-11-LABX-0047]. The research of V. Goyal was supported in part by the Defense Advanced Research Projects Agency [Grant Lagrange] and the Division of Civil, Mechanical and Manufacturing Innovation [Grant 1636046]. This work was also supported by the Division of Civil, Mechanical and Manufacturing Innovation [Grants 1350059 and 1351838] and the Columbia Business School [Deming Fellowship 2019]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/opre.2022.2403. [ABSTRACT FROM AUTHOR]

Markov decision processes (MDPs) are used to model stochastic systems in many applications, but computing good policies becomes hard when the effective horizon become very large. In "A First-Order Approach to Accelerated Value Iteration," Goyal and Grand-Clément present a connection between value iteration (VI) algorithms and gradient descent methods from convex optimization and use acceleration and momentum to design faster algorithms, with convergence guarantees for the computation of the value function of a fixed policy for reversible MDP instances. The authors provide a lower bound on the convergence properties of any first-order algorithm for solving MDPs, where no algorithm can converge faster than VI. Finally, the authors introduce safe accelerated value iteration (S-AVI), which alternates between accelerated updates and value iteration updates. The algorithm S-AVI is worst-case optimal and retains the theoretical convergence properties of VI while exhibiting strong empirical performances and providing significant speedups when compared with classical approaches for a large test bed of MDP instances. Markov decision processes (MDPs) are used to model stochastic systems in many applications. Several efficient algorithms to compute optimal policies have been studied in the literature, including value iteration (VI) and policy iteration. However, these do not scale well, especially when the discount factor for the infinite horizon discounted reward, λ, gets close to one. In particular, the running time scales as O (1 / (1 − λ)) for these algorithms. In this paper, our goal is to design new algorithms that scale better than previous approaches when λ approaches 1. Our main contribution is to present a connection between VI and gradient descent and adapt the ideas of acceleration and momentum in convex optimization to design faster algorithms for MDPs. We prove theoretical guarantees of faster convergence of our algorithms for the computation of the value function of a policy, where the running times of our algorithms scale as O (1 / 1 − λ ) for reversible MDP instances. The improvement is quite analogous to Nesterov's acceleration and momentum in convex optimization. We also provide a lower bound on the convergence properties of any first-order algorithm for solving MDPs, presenting a family of MDPs instances for which no algorithm can converge faster than VI when the number of iterations is smaller than the number of states. We introduce safe accelerated value iteration (S-AVI), which alternates between accelerated updates and value iteration updates. Our algorithm S-AVI is worst-case optimal and retains the theoretical convergence properties of VI while exhibiting strong empirical performances and providing significant speedups when compared with classical approaches (up to one order of magnitude in many cases) for a large test bed of MDP instances. Funding: J. Grand-Clément is supported by a grant of the French National Research Agency (ANR), "Investissements d'Avenir" [Grant LabEx Ecodec/ANR-11-LABX-0047] and by Hi! Paris. The research of V. Goyal was supported in part by the Defense Advanced Research Projects Agency [Grant Lagrange] and the Division of Civil, Mechanical and Manufacturing Innovation [Grant 1636046]. [ABSTRACT FROM AUTHOR]

Background: Multiple clinical practice guidelines recommend minimizing radiation in trauma patients but there is a knowledge gap on the importance of this problem for trauma transfers. We aimed to estimate the incidence of pretransfer and repeat posttransfer computed tomography (CT) overall and in patients with an indication for immediate transfer, to assess interhospital practice variation, to identify predictors, and to quantify the influence of pretransfer CT on time to transfer. Methods We conducted a retrospective multicenter cohort study on patients transferred to major trauma centers from 2013 to 2019. Multilevel generalized linear regression was used to generate intraclass correlation coefficients (ICCs) to assess interhospital variation, multilevel logistic regression to generate odds ratios for each predictor, and geometric mean ratios to quantify the influence of CT on time to transfer. Results Of 18,244 patients included, 8501 (47%) had a pretransfer CT and one‐quarter (26%) had a repeat posttransfer CT. Interhospital variation was moderate for pretransfer CT (5%–66%, ICC 12.5%) and for repeat posttransfer CT (7%–44%, ICC 14.7%). Pretransfer imaging was more frequent in elders and in males and repeat posttransfer imaging decreased over the study period but was more frequent in patients transferred in from Level III/IV centers than nondesignated hospitals. Time to transfer was doubled in patients who had a pretransfer CT. Conclusions: Results suggest that pretransfer CT and repeat posttransfer CT are frequent and are subject to significant practice variation. In addition, pretransfer CT is associated with increased times to transfer though additional studies are needed to demonstrate causation. These results highlight potential opportunities to reduce low‐value imaging for trauma transfers. [ABSTRACT FROM AUTHOR]

Background: Training volume can be estimated for players in team sports using inertial measurement units. Specific variables such as jumps and jump intensity have shown correlation with fatigue markers in players at the goalkeeper position. Therefore, the goal of this study was to explore the feasibility of analyzing training volume and intensity for water polo goalkeepers using IMU variables. Methods: Three senior national water polo team female goalkeepers were recruited for this study. Data from seven training sessions and seven international matches were recorded. Training volume was calculated and specific events were counted (jumps and kicks). Activity intensity score was calculated as a proportion of time spent in high-intensity activities. A paired t test was performed to compare training and match conditions. Results: The mean duration of training sessions was significantly shorter than matches (74.4 ± 14.4 min vs 91.4 ± 5.4 min, p < 0.01). The mean activity intensity score was also significantly lower in training sessions vs. matches (47.9 ± 3.5% vs 58.6 ± 3.8%, p = 0.04). Acceleration rate of change per minute was not different between training and matches (p = 0.10). Conclusion: This study showed the feasibility of using IMU to provide meaningful training and match metrics in a small sample of female water polo goalkeepers. This type of analysis can be used to describe both volume and intensity of training in future studies. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Surgery is the property of CMA Impact Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Surgery is the property of CMA Impact Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Guidelines for injury care are increasingly moving away from surgical management towards less invasive procedures but there is a knowledge gap on how these recommendations are influencing practice. We aimed to assess inter‐hospital variation in surgical intensity for injury admissions and evaluate the correlation between hospital surgical intensity and mortality/complications. Methods: We included adults admitted for major trauma between 2006 and 2016 in a Canadian provincial trauma system. Analyses were stratified for orthopaedic (n = 16 887), neurological (n = 12 888) and torso injuries (n = 9816). Surgical intensity was quantified with the number of surgical procedures <72 hours. Inter‐hospital variation was assessed with the intra‐class correlation coefficient (ICC). We assessed the correlation between the risk‐adjusted mean number of surgical procedures and risk‐adjusted incidence of mortality and complications using Pearson correlation coefficients (r). Results: Moderate inter‐hospital variation was observed for orthopaedic surgery (ICC = 14.0%) whereas variation was low for torso surgery (ICC = 2.7%) and neurosurgery (ICC = 0.8%). Surgical intensity was negatively correlated with hospital mortality for torso injury (r = −.32, P =.02) and neurotrauma (r = −.65, P =.08). A strong positive correlation was observed with hospital complications for orthopaedic injuries (r =.36, P =.006) whereas the opposite was observed for neurotrauma (r = −.71, P =.05). Conclusions: Results should be interpreted with caution as they may be a result of residual confounding. However, they may suggest that there are opportunities for quality improvement in surgical care for injury admissions, particularly for orthopaedic injuries. Moving forward, we should aim to prospectively evaluate adherence to guidelines on non‐operative management and their impact on mortality and morbidity. [ABSTRACT FROM AUTHOR]

Fragility curves (FCs) are key tools for seismic probabilistic safety assessments that are performed at the level of the nuclear power plant (NPP). These statistical methods relate the probabilistic seismic hazard loading at the given site to the required performance of the NPP safety functions. In the present study, we investigate how the tools of non-stationary extreme value analysis can be used to model in a flexible manner the tail behaviour of the engineering demand parameter as a function of the considered intensity measure. We focus the analysis on the dynamic response of an anchored steam line and of a supporting structure under seismic solicitations. The failure criterion is linked to the exceedance of the maximum equivalent stress at a given location of the steam line. A series of three-component ground-motion records (∼300) were applied at the base of the model to perform non-linear time history analyses. The set of numerical results was then used to derive a FC, which relates the failure probability to the variation in peak ground acceleration (PGA). The probabilistic model of the FC is selected via information criteria completed by diagnostics on the residuals, which support the choice of the generalised extreme value (GEV) distribution (instead of the widely used log-normal model). The GEV distribution is here non-stationary, and the relationships of the GEV parameters (location, scale and shape) are established with respect to PGA using smooth non-linear models. The procedure is data-driven, which avoids the introduction of any a priori assumption on the shape or form of these relationships. To account for the uncertainties in the mechanical and geometrical parameters of the structures (elastic stiffness, damping, pipeline thicknesses, etc.), the FC is further constructed by integrating these uncertain parameters. A penalisation procedure is proposed to set to zero the variables of little influence in the smooth non-linear models. This enables us to outline which of these parametric uncertainties have negligible influence on the failure probability as well as the nature of the influence (linear, non-linear, decreasing, increasing, etc.) with respect to each of the GEV parameters. [ABSTRACT FROM AUTHOR]

Background Injuries represent one of the leading causes of preventable morbidity and mortality. For countries with ageing populations, admissions of injured older patients are increasing exponentially. Yet, we know little about hospital resource use for injured older patients. Our primary objective was to evaluate inter-hospital variation in the risk-adjusted resource use for injured older patients. Secondary objectives were to identify the determinants of resource use and evaluate its association with clinical outcomes. Methods We conducted a multicenter retrospective cohort study of injured older patients (≥65 years) admitted to any trauma centres in the province of Quebec (2013–2016, N  = 33,184). Resource use was estimated using activity-based costing and modelled with multilevel linear models. We conducted separate subgroup analyses for patients with trauma and fragility fractures. Results Risk-adjusted resource use varied significantly across trauma centres, more for older patients with fragility fractures (intra-class correlation coefficients [ICC] = 0.093, 95% CI [0.079, 0.102]) than with trauma (ICC = 0.047, 95% CI = 0.035–0.051). Risk-adjusted resource use increased with age, and the number of comorbidities, and varied with discharge destination (P  < 0.001). Higher hospital resource use was associated with higher incidence of complications for trauma (Pearson correlation coefficient r  = 0.5, 95% CI = 0.3–0.7) and fragility fractures (r  = 0.5, 95% CI = 0.3–0.7) and with higher mortality for fragility fractures (r  = 0.4, 95% CI = 0.2–0.6). Conclusions We observed significant inter-hospital variations in resource use for injured older patients. Hospitals with higher resource use did not have better clinical outcomes. Hospital resource use may not always positively impact patient care and outcomes. Future studies should evaluate mechanisms, by which hospital resource use impacts care. [ABSTRACT FROM AUTHOR]

Water polo players benefit from greater odds of success when maintaining their tactical position against their opponents. This study evaluated the reliability and validity of a water-based resistance test to replicate this skill.Thirty-three water polo players participated in this study (19 males and 14 females, 14 from senior and 19 from junior national teams). Data were collected during two regular training sessions, separated by one week, using a load cell to instrument a weight stack resistance setup on the pool deck. Performance parameters such as mean force, maximum force, mean peak force and total impulse were defined with custom Python scripts. Test-retest reliability was assessed using intra-class correlations (ICC3,1). Group comparisons were explored between male and female players. Level of significance was set at p < 0.05. The reliability findings were high to very high for the mean force, maximum force, mean peak force, inter-stroke range, and total impulse (ICC 0.85 - 0.93, p < 0.01). Group comparisons showed significantly greater values in male players for these variables (p < 0.01, ES = 1.05 - 9.36) with large to very large effect sizes. However, there was no significant difference in endurance measured between sexes (p = 0.88, ES = 0.04). This study presents a methodology with satisfactory metrological qualities for field applications using simple and affordable equipment. The testing apparatus presented in this study can readily be replicated in a variety of training environments by practitioners working with water polo teams. Coaches can use this approach to evaluate individual player progress or to compare performance across a group of water polo players. [ABSTRACT FROM AUTHOR]

Objectives: The Quebec Trauma Care Continuum (TCC) was initiated in 1991 with the objective of providing accessible, continuous, efficient, and high quality services for all injury cases in the province. Methods: The TCC design relied on three key components: (i) the designation of a network of acute care and rehabilitation facilities with specific mandates and responsibilities; (ii) the elaboration of transfer protocols, standing agreements, and governing structures to ensure fluid and optimal patient flow; and (iii) the close monitoring of several indicators to facilitate the continuous evaluation and improvement of the network. Results: Between 1992 and 2002, in-hospital mortality following major trauma decreased from 51.8 percent to 8.6 percent, followed by an additional 24 percent drop between 1999 and 2012. We also observed a 16 percent decrease in average LOS but no change in the incidence of complications or unplanned readmissions. These changes translate into 186 lives saved per year and cost savings, due to shorter LOS, of 6.3 million CD$ per year. The risk-adjusted incidence of in-hospital mortality following major injury between 2006 and 2012 (7 percent) was the lowest of all Canadian provinces. Conclusions: Strategic transformation of a network’s structure and processes, supported by continuous monitoring of validated quality indicators, can lead to significant and sustainable improvements in clinical outcomes. It is hoped that the Quebec trauma story will inspire other jurisdictions and other healthcare sectors. [ABSTRACT FROM AUTHOR]