University of Verona
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In vitro activity of cefepime/zidebactam against sulbactam/durlobactam-susceptible and -resistant Acinetobacter baumannii clinical isolates
No full textObjectives: To evaluate the in vitro activity of cefepime in association with a β-lactamase inhibitor (enmetazobactam) or β-lactam enhancer (BLE), zidebactam, against carbapenem-resistant Acinetobacter baumannii (CRAB) strains susceptible or resistant to sulbactam/durlobactam. Material and methods: Twenty-one CRAB clinical isolates were characterized by WGS and AST to cefepime/enmetazobactam, cefepime/zidebactam and comparators was determined. Results: Resistome analysis revealed that all CRAB carried blaOXA-23 carbapenemase genes, while blaADC-25 and blaOXA-66 β-lactamase genes were observed exclusively in sulbactam/durlobactam-resistant strains. Analysis of penicillin-binding protein genes demonstrated the presence of specific mutations within PBP3 (N392T) previously associated to the resistance to sulbactam/durlobactam. Phenotypic analysis revealed that cefepime/enmetazobactam did not exert antibacterial activity against CRAB, while cefepime/zidebactam displayed potent bactericidal activity against both sulbactam/durlobactam-susceptible and -resistant strains. Conclusions: These results demonstrate that cefepime/zidebactam exhibited potent in vitro antibacterial activity against CRAB producing OXA carbapenemase and support its clinical use against both sulbactam/durlobactam-susceptible or -resistant isolates
Passive Reinforcement Learning with Optimal Control for Safe Convergence in Cyber–physical Systems
Full text linkReinforcement Learning (RL) can compute optimal strategies for accomplishing difficult tasks in complex scenarios. However, most RL algorithms do not provide safety and performance guarantees during the deployment phase. This is a critical drawback when RL is applied to cyber–physical systems such as robotic manipulators, where the goal is to always and safely converge to a desired goal or equilibrium state. Specifically, one fundamental safety requirement for robotic systems is closed-loop L2-stability, which has passivity as a sufficient condition. This paper proposes a novel switched RL control scheme for robotic systems, with passivity and asymptotic stability guarantees. This combines RL over constrained Markov decision processes, for passive training and inference, with Linear Quadratic Regulation (LQR) for asymptotic convergence to the desired equilibrium point. During RL training, the energy stored in the system is monitored via the virtual energy tank approach to train a cost critic function. During inference, the virtual energy tank modulates the command input to guarantee passivity. Finally, the reward design of the RL agent is based on the Lyapunov function associated with LQR control, in order to steer the system state towards the LQR basin of attraction, where a switching mechanism is triggered to guarantee asymptotic convergence. We compare our methodology with a model-based controller and other RL and model-based architectures applied to a paradigmatic under-actuated cart–pole system, an instance of a 2-DOF robotic manipulator, both in simulation and on a real setup. We also test the generality of our approach, with an experiment on a 6-DOF manipulator in simulation. The experimental validation shows that our methodology performs better in training and inference, even in the presence of plant modelling errors, while guaranteeing passivity and safety in the presence of large disruptive disturbances
Time-dependent effects in consecutive cycles of prone positioning for acute respiratory failure: insights from the PROVENT-C19 Registry
No full textBackground: Prone positioning is recommended for patients with acute respiratory distress syndrome not only to improve oxygenation, but also to reduce lung stress, and lower mortality. The association between improved oxygenation during prone position and reduced mortality is still controversial. In previous studies, oxygenation improvement during the first prone positioning cycle was linked to lower intensive care unit (ICU) mortality, especially with prolonged duration. However, physiological data during subsequent cycles were lacking. This study aims to explore the association between ICU mortality and physiological responses to prone positioning-such as arterial oxygenation, dead space, and respiratory mechanics-and to assess how the cumulative time spent in prone or supine positions across all studied cycles influences outcomes. Methods: International registry including adult patients who underwent prone positioning for acute hypoxemic respiratory failure due to COVID-19. We measured the difference for arterial partial pressure of oxygen to inspired fraction of oxygen ratio (PaO2/FiO2) and ventilatory ratio between baseline supine position and at either the end of cycle of prone position (Delta-PP) or re-supination (Delta-PostPP), focusing on the cycles following the first one. Results: We included 1523 patients from 53 centers. Both Delta-PP and Delta-PostPP for PaO2/FiO2 were significantly higher in ICU survivors than in ICU non-survivors for all the analyzed prone positioning cycles (p ≤ 0.001 for all comparisons). Delta-PP and Delta-PostPP for ventilatory ratio were significantly lower in ICU survivors than in ICU non-survivors for all the analyzed prone positioning cycles (p < 0.05 for all comparisons). No difference in the overall time spent in prone position was found between ICU survivors and non-survivors [61 (38, 84) h vs 58 (32, 85) h, respectively, p = 0.175]. The cumulative length of prone position was associated with ICU mortality only for the second prone positioning cycle [OR (95% CI) 0.986 (0.978, 0.994)]. No significant association was observed between the time spent in supine position and ICU mortality for all the analyzed prone positioning cycles. Conclusions: ICU survivors consistently demonstrated better oxygenation and more stable ventilatory ratio across studied prone positioning cycles, whereas non-survivors showed worsening oxygenation when returning supine and increased ventilatory ratio. Additionally, extending the duration of prone position beyond the second cycle may not significantly impact mortality
Does baseline severity interact with the effects of psychotherapy for depression? A meta-analytic review
Full text linkIntroduction: It is not yet clear whether baseline severity is associated with the effects of psychotherapies. We examined baseline severity at the study level in a large sample of randomized controlled trials comparing psychotherapies against a control condition for the treatment of depression. Methods: We used an existing large database of randomized trials comparing psychotherapies for depression with control groups (www.metapsy.org). We converted baseline severity scores across different depression measures into a common metric. We ran bivariable and multivariable meta-regression analyses to examine the association of effect sizes with baseline severity. We also examined response rates in treatment and control conditions. Results: We included 387 randomized trials (463 comparisons; 47,315 patients). The pooled effect size of the psychotherapies was g = 0.77 (95 % CI, 0.70; 0.84). In the main analyses, we found a highly significant association between the effect size and baseline severity (bivariable coefficient: 0.024 (SE = 0.006; p < 0.0001), multivariable coefficient: 0.022 (SE = 0.007; p = 0.002)). This was confirmed in some but not all sensitivity analyses. Absolute response rates in the control conditions remained stable across different levels of baseline severity (bivariable metaregression analyses: p = 0.545), or showed a negative association (multivariable analyses: p = 0.002). In the therapy conditions the response rates were significantly larger with increasing levels of baseline severity (bivariable: p ≤0.0001; multivariable: p = 0.006). Conclusion: The effects of psychotherapies are probably associated with baseline severity. Response rates in control conditions remained relatively stable across different levels of baseline severity, while in the treatment conditions the response rates increased with increasing levels of baseline severity
Trends and demographic patterns of portal vein thrombosis mortality in the United States, 2018–2024
No full textTrends and demographic patterns of portal vein thrombosis mortality in the United States, 2018–202
Exponential quadrature rules for problems with time-dependent fractional source
Full text linkIn this manuscript, we propose newly-derived exponential quadrature rules for stiff linear differential equations with time-dependent fractional sources in the form , with 0<1 and a sufficiently smooth function. To construct the methods, the source term is interpolated at collocation points by a suitable non-polynomial function, yielding to time marching schemes that we call Exponential Quadrature Rules for Fractional sources (EQRF). The error analysis is done in the framework of strongly continuous semigroups. Compared to classical exponential quadrature rules, which in our case of interest converge with order at most, we prove that the new methods may reach order for proper choices of the collocation points. We also show that the proposed integrators can be written in terms of special instances of the Mittag--Leffler functions that we call fractional functions. Several numerical experiments demonstrate the theoretical findings and highlight the effectiveness of the approach
Assessing postural balance control in young dinghy sailors pre, during and post training sessions
Full text linkObjective: This study examined the acute effect of training on postural balance among young dinghy sailors. By measuring sway path and sway area of the center of pressure (CoP), the objective was to investigate whether training sessions on dinghy sailboat influence sway path and sway area measurements. Methods: Twelve competitive sailors (Optimist and Laser Radial class) performed a set of balance tests on both stable and unstable surfaces, with open and closed eyes, measured over three days. The first day served to familiarize the participants with the protocol. On the second and third days, CoP sway path and sway areas were assessed before, during and after the training session using a Wii Balance Board (WBB). Results: A general improvement in balance control was observed in most of the measured parameters. Statistical analysis (RM ANOVA) revealed significant reductions in sway path and sway area with closed eyes on an unstable surface comparing pre-, during- and post- measurement on the second day (p < 0.05), and for sway path with open and closed eyes on an unstable surface on the third day (p < 0.05). Conclusion: Findings of the present study show a short-term effect of sailing sessions on balance, suggesting that a single training session can induce acute improvements in postural control among young athletes. It is possible that the observed acute improvements are associated with immediate neuromuscular adaptation following sailing activity, specifically due to the unpredictable and dynamic environment in which sailing takes place. However, the temporal duration of this effect appears to be limited. As balance is an essential skill in sailing performance, future studies should investigate long-term effects and retention of training-induced improvements in postural control
Lessons from the European Mpox Outbreak: Strengthening Cohort Research for Future Pandemic Preparedness
No full textBackground: Well-designed cohort studies are crucial for pandemic preparedness informing evidence-based infection prevention and treatment strategies. Objectives: Following the 2022 mpox outbreak in Europe, this scoping review critically evaluates the design, implementation, and characteristics of cohort studies focusing on mpox. The aim is to inform recommendations for the Cohort Coordination Board and CoMeCT to enhance cohort study research and improve preparedness. Sources: A comprehensive literature search was conducted in PubMed, Scopus, ClinicalTrials.gov, the EU Clinical Trials Register, and the ECRIN metadata repository up to December 2024. Content: Forty-nine cohorts were identified, encompassing 10,728 individuals with primary or breakthrough mpox and 34,010 individuals without mpox (vaccinated and unvaccinated). The majority of cohorts collected data prospectively (30, 63%) and were multicentre (25, 52%). The primary aims were natural history of mpox (31, 65%); effectiveness of vaccination (15, 31%); and treatment (2, 4%). The most frequent target population was individuals at increased risk of sexually transmitted infection (18, 38%). Follow up of participants varied widely among cohorts. Significant data heterogeneity, stemming from the inconsistent use of standardised data dictionaries, impeded data sharing and meta-analyses. Under-representation of vulnerable populations and limited biobanking further compounded these challenges. Implications: This review underscores critical gaps in the research response during the mpox outbreak. Based on these findings, we propose the following recommendations: (1) Establishing and maintaining "ever-warm" cohorts of high-risk individuals during inter-epidemic periods to enable rapid data collection during future outbreaks; (2) Promoting data interoperability through the development and adoption of standardised data collection tools, and ontologies; (3) Improving the quality of study reporting through strict adherence to relevant guidelines; and (4) Strengthening European and global coordination through the establishment of collaborative research networks. Sustained investment in research infrastructure is essential for a more effective, equitable, and timely public health response to future outbreaks
Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide, and Tirzepatide in Adults With Type 2 Diabetes
No full textBackground: The comparative gastrointestinal safety across glucagon-like peptide-1 receptor agonists and tirzepatide is still unclear. Objective: To compare the risk for severe gastrointestinal adverse events across dulaglutide, subcutaneous semaglutide, and tirzepatide in patients with type 2 diabetes (T2D) in routine clinical practice. Design: New-user, active-comparator cohort study. Setting: Population-based study. Participants: Adults with T2D initiating dulaglutide, subcutaneous semaglutide, and tirzepatide between 1 January 2019 and 30 August 2024 in 3 cohorts corresponding to 3 pairwise comparisons. Measurements: The primary outcome was a composite of acute pancreatitis, biliary disease, bowel obstruction, gastroparesis, and severe constipation. Secondary outcomes of interest were the individual components of the primary outcome. Patients were 1:1 propensity score matched within each comparison. We calculated hazard ratios (HRs) with 95% CIs. Results: There were 65 238 matched pairs in the semaglutide versus dulaglutide cohort, 20 893 in the tirzepatide versus dulaglutide cohort, and 46 620 in the tirzepatide versus semaglutide cohort. The HR of gastrointestinal events was 0.96 (95% CI, 0.87 to 1.06) in the semaglutide versus dulaglutide cohort, 0.96 (CI, 0.77 to 1.20) in the tirzepatide versus dulaglutide cohort, and 1.07 (CI, 0.90 to 1.26) in the tirzepatide versus semaglutide cohort. Limitation: Possible residual confounding by glycemic control and body mass index. Conclusion: These findings suggest that dulaglutide, semaglutide, and tirzepatide have similar gastrointestinal safety profiles in adults with T2D. This study provides clinicians with evidence to weigh the benefits and risks of these medications. Primary funding source: National Institute of Diabetes and Digestive and Kidney Diseases
Assessing the Relationship and Convergent Validity of Player Load and Dynamic Stress Load in Basketball: A Multivariable Regression Analysis
No full textPurpose: This study aimed to assess the strength of the relationship between Player Load and dynamic stress load (DSL); to evaluate the convergent validity between Player Load, DSL, and other external-load parameters in basketball; and to develop multiple-regression models to explain the relative importance of different external-load parameters to Player Load and DSL. Methods: Thirteen male basketball players less than 18 years old (age: 16.9 y, height: 198.1 cm, and body mass: 80.2 kg) participated in this study during the 2023-24 season. Players' physical demands were monitored with a local positioning system that was combined with inertial microsensors (WIMU PRO, RealTrack Systems SL). The accelerometer-derived metrics analyzed in this study were Player Load and DSL and other external-load metrics. Results: Player Load and DSL showed a very large repeated-measure relationship, rm_corr = .781. Player Load showed a relationship with total distance (.967, almost perfect), high-speed running (.687, large), acceleration distance (.680, large), and deceleration distance (.661, large). Dynamic stress load showed a significant relationship with total distance (.662, large), high-speed running (.663, large), acceleration distance (.426, moderate), and deceleration distance (.412, moderate). Conclusions: Player Load and DSL are correlated but not interchangeable. Player Load correlates at least moderately with all external-load measures monitored, with total distance and step count being almost perfect. Although DSL is correlated well with impacts, step count, and jump count over 3 gravitational forces, it correlates to a lesser extent with all metrics. Finally, this study developed 2 multiple-regression models to explain the relative importance of external-load parameters