Bayes beyond the predictive distribution.

Binz et al. argue that meta-learned models offer a new paradigm to study human cognition. Meta-learned models are proposed as alternatives to Bayesian models based on their capability to learn identical posterior predictive distributions. In our commentary, we highlight several arguments that reach beyond a predictive distribution-based comparison, offering new perspectives to evaluate the advantages of these modeling paradigms.

2022 Equine community needs assessment survey.

To stay up-to-date with the demographics, interests, and needs of the equine community, equine extension programs commonly conduct so called "needs assessment surveys". The main goals of the 2022 Rutgers Equine Science Center (ESC) needs assessment survey were to: 1) characterize the equine community, 2) identify information sources used by the equine community, 3) assess the usefulness of selected equine-related services and programs, and 4) determine the perceived importance of selected equine-related issues. An anonymous online survey was distributed through the Rutgers ESC's email list, a press release, and social media. Analysis-eligible surveys were received from n = 493. Most participants were female (92.7 %), 36-60 years of age (48.4 %), white (88.8 %), and horse owners (87.8 %). The top three sources of equine-related information used were 1) personal knowledge (95.7 %), 2) the veterinarian (93.7 %), and 3) the farrier (83.7 %). The survey showed that the provision of horse health information is the most useful service that the Rutgers ESC specifically can provide (79.3 %). This service may also be most useful for other extension programs, but a follow-up study is needed for clarification. The five equine-related issues most often considered to be extremely important were "Lameness and Soundness" (76.5 %), "Ethical Use of Horses" (73.2 %), "Nutrition" (63.9 %), "Right to Farm" (56.8 %), and "Care of Old Horses" (55.6 %). The survey provided insights into the current demographics of the equine community, highlighted personal knowledge, veterinarians and farriers as important information sources, and elucidated "Lameness and Soundness" as the most important equine-related issue.

SAME day amBulatory c (SAMBA): a multicenter, prospective, randomized clinical trial protocol.

BACKGROUND: A recent meta-analysis concluded that outpatient appendectomy appears feasible and safe, but there is a lack of high-quality evidence and a randomized trial is needed. The aim of this trial is to demonstrate that outpatient appendectomy is non-inferior to conventional inpatient appendectomy in terms of overall morbi-mortality on the 30th postoperative day (D30). METHODS: SAMBA is a prospective, randomized, controlled, multicenter non-inferiority trial. We will include 1400 patients admitted to 15 French hospitals between January 2023 and June 2025. Inclusion criteria are patients aged between 15 and 74 years presenting acute uncomplicated appendicitis suitable to be operated by laparoscopy. Patients will be randomized to receive outpatient care (day-surgery) or conventional inpatient care with overnight hospitalization in the surgery department. The primary outcome is postoperative morbi-mortality at D30. Secondary outcomes include time from diagnosis to appendectomy, length of total hospital stay, re-hospitalization, interventional radiology, re-interventions until D30, conversion from outpatient to inpatient, and quality of life and patient satisfaction using validated questionnaires. DISCUSSION: The SAMBA trial tests the hypothesis that outpatient surgery (i.e., without an overnight hospital stay) of uncomplicated acute appendicitis is a feasible and reliable procedure in establishments with a technical platform able to support this management strategy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05691348. Registered on 20 January 2023.

Factors predicting mortality in the cardiac ICU during the early phase of targeted temperature management in the treatment of post-cardiac arrest syndrome - The RAPID score.

Introduction: Survival rates after out-of-hospital cardiac arrest (OHCA) remain low, and early prognostication is challenging. While numerous intensive care unit scoring systems exist, their utility in the early hours following hospital admission, specifically in the targeted temperature management (TTM) population, is questionable. Our aim was to create a score system that may accurately estimate outcome within the first 12 h after admission in patients receiving TTM. Methods: We analyzed data from 103 OHCA patients who subsequently underwent TTM between 2016 and 2022. Patient demographic data, prehospital characteristics, clinical and laboratory parameters were already available in the first 12 h after admission were collected. Following a bootstrap-based predictor selection, we constructed a nonlinear logistic regression model. Internal validation was performed using bootstrap resampling. Discrimination was described using the c-statistic, whereas calibration was characterized by the intercept and slope. Results: According to the Akaike Information Criterion (AIC) heart rate (AIC = 9.24, p = 0.0013), age (AIC = 4.39, p = 0.0115), pH (AIC = 3.68, p = 0.0171), initial rhythm (AIC = 4.76, p = 0.0093) and right ventricular end-diastolic diameter (AIC = 2.49, p = 0.0342) were associated with 30-day mortality and were used to build our predictive model and nomogram. The area under the receiver-operating characteristics curve for the model was 0.84. The model achieved a C-statistic of 0.7974, with internally validated acceptable calibration (intercept: -0.0190, slope: 0.7772) and low error rates (mean absolute error: 0.040). Conclusion: The model we have developed may be suitable for early risk assessment of patients receiving TTM as part of primary post-resuscitation care. The calculator needed for scoring can be accessed at the following link: https://www.rapidscore.eu/.

Weekend endoscopic retrograde cholangiopancreatography has similar outcomes as weekday procedures-a propensity score match analysis of the Hungarian ERCP Registry.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for the minimally invasive management of biliary and pancreatic disorders. Under certain indications, performing ERCP without delay during the weekend can be important for improving outcomes. Objectives: To compare the outcomes of ERCP performed on weekends and holidays with those of regular weekday ERCPs. Design: Propensity score match analysis of the data from the Hungarian ERCP Registry. Methods: A total of 116 ERCPs were performed during weekends or holidays, and 3144 during weekday working hours. The analyses were performed on 1:2 propensity-matched groups (116 weekend and 232 weekday cases). Results: Weekend ERCPs were mostly performed for acute cholangitis and acute biliary pancreatitis (70% of cases), whereas in the weekday group, only 32% of cases were performed for these indications. No significant difference was found between weekday and weekend ERCPs in terms of the rates of successful (91.38% vs 93.1%, p = 0.565) and difficult (33.62% vs 36.64%, p = 0.511) biliary cannulations. We found no significant differences in the number of adverse events (bleeding, post-ERCP pancreatitis, and 30-day mortality) in ERCPs performed during weekends or weekdays. Moreover, no significant differences in the aforementioned outcomes were detected between the propensity-matched groups. Conclusion: In this propensity-matched study, no significant differences were found in the outcomes of weekend and weekday ERCPs.

Prediction of transfusion risk after total knee arthroplasty: use of a machine learning algorithm.

INTRODUCTION: Total knee arthroplasty (TKA) carries a significant hemorrhagic risk, with a non-negligible rate of postoperative transfusions. The blood-sparing strategy has evolved to reduce blood loss after TKA by identifying the patient's risk factors preoperatively. In practice, a blood count is often performed postoperatively but rarely altering the patient's subsequent management. This study aimed to identify the preoperative variables associated with hemorrhagic risk, enabling the creation of a machine-learning model predictive of transfusion risk after total knee arthroplasty and the need for a complete blood count. HYPOTHESIS: Based on preoperative data, a powerful machine learning predictive model can be constructed to estimate the risk of transfusion after total knee arthroplasty. MATERIAL AND METHODS: This retrospective single-centre study included 774 total knee arthroplasties (TKA) operated between January 2020 and March 2023. Twenty-five preoperative variables were integrated into the machine learning model and filtered by a recursive feature elimination algorithm. The most predictive variables were selected and used to construct a gradient-boosting machine algorithm to define the overall postoperative transfusion risk model. Two groups were formed of patients transfused and not transfused after TKA. Odds ratios were determined, and the area under the curve evaluated the model's performance. RESULTS: Of the 774 TKA surgery patients, 100 were transfused postoperatively (12.9%). The machine learning predictive model included five variables: age, body mass index, tranexamic acid administration, preoperative hemoglobin level, and platelet count. The overall performance was good with an area under the curve of 0.97 [95% CI 0.921 - 1], sensitivity of 94.4% [95% CI 91.2 - 97.6], and specificity of 85.4% [95% CI 80.6 - 90.2]. The tool developed to assess the risk of blood transfusion after TKA is available at https://arthrorisk.com. CONCLUSION: The risk of postoperative transfusion after total knee arthroplasty can be predicted by a model that identifies patients at low, moderate, or high risk based on five preoperative variables. This machine learning tool is available on a web platform that is accessible to all, easy to use, and has a high prediction performance. The model aims to limit the need for routine check-ups, depending on the risk presented by the patient. LEVEL OF EVIDENCE: II; diagnostic study.

Identifying Transfer Learning in the Reshaping of Inductive Biases.

Transfer learning, the reuse of newly acquired knowledge under novel circumstances, is a critical hallmark of human intelligence that has frequently been pitted against the capacities of artificial learning agents. Yet, the computations relevant to transfer learning have been little investigated in humans. The benefit of efficient inductive biases (meta-level constraints that shape learning, often referred as priors in the Bayesian learning approach), has been both theoretically and experimentally established. Efficiency of inductive biases depends on their capacity to generalize earlier experiences. We argue that successful transfer learning upon task acquisition is ensured by updating inductive biases and transfer of knowledge hinges upon capturing the structure of the task in the inductive bias that can be reused in novel tasks. To explore this, we trained participants on a non-trivial visual stimulus sequence task (Alternating Serial Response Times, ASRT); during the Training phase, participants were exposed to one specific sequence for multiple days, then on the Transfer phase, the sequence changed, while the underlying structure of the task remained the same. Our results show that beyond the acquisition of the stimulus sequence, our participants were also able to update their inductive biases. Acquisition of the new sequence was considerably sped up by earlier exposure but this enhancement was specific to individuals showing signatures of abandoning initial inductive biases. Enhancement of learning was reflected in the development of a new internal model. Additionally, our findings highlight the ability of participants to construct an inventory of internal models and alternate between them based on environmental demands. Further, investigation of the behavior during transfer revealed that it is the subjective internal model of individuals that can predict the transfer across tasks. Our results demonstrate that even imperfect learning in a challenging environment helps learning in a new context by reusing the subjective and partial knowledge about environmental regularities.

Enhancing self-management of patients with inflammatory bowel disease: the role of autonomy support in health goal pursuit.

Background: Inflammatory bowel disease (IBD) is a chronic condition that significantly affects patients' physical, mental, and social health, as well as their overall quality of life. Effective management of the disease demands self-management skills, enabling patients to navigate the daily challenges associated with IBD, such as unpredictable flare-ups, frequent hospitalization, severe symptoms, pain, and physical changes. Objectives: This study examines the motivational aspects of self-management for patients with IBD and focuses on the role of autonomy and directive support from healthcare professionals in enhancing their self-concordance and self-efficacy. Design: From November 2022 to February 2023, a cross-sectional questionnaire study was conducted at the IBD Center of Internal Medicine Clinic in Szeged, Hungary. Methods: A total of 374 adult patients with IBD completed the paper-pencil questionnaire, of whom 241 patients (64.4%) had Crohn's disease, and 133 patients (35.6%) had ulcerative colitis. Results: Based on the findings of the path analysis (χ2 (8) = 18.914, p = 0.01, comparative fit index = 0.935, TLI = 0.837, root mean squared error of approximation = 0.06), autonomy support positively predicted self-concordance (ß = 0.48) and self-efficacy (ß = 0.02), particularly during disease relapse. In addition, self-concordance and self-efficacy predicted more positive (ßs = 0.28 and 0.35) and fewer negative emotional experiences (ßs = -0.09 and -0.20). The model's associations varied between the relapse and remission groups, indicating distinct impacts on different states of the disease. Conclusion: Overall, autonomy support from healthcare professionals has been shown to enhance self-management in patients with IBD, particularly during disease relapse. Meanwhile, self-concordance and self-efficacy act as positive internal factors, thus reducing negative emotional experiences, especially during remission. In sum, this study underscores the need for further exploration of the motivational aspects of self-management and provides insights into developing interventions that promote the health behaviors of patients with IBD.

Self-management of inflammatory bowel disease patients Autonomy support from healthcare professionals has been shown to significantly improve the effectiveness of self-management in patients with inflammatory bowel disease (IBD) (especially during disease relapse), by enhancing their self-concordance and self-efficacy. In this case, the interplay between disease activity, positive and negative emotions, and self-regulatory mechanisms underscores the importance of examining the motivational aspects for developing interventions that promote health behaviors in patients with IBD.

Heparin-like effect of a dual antiplatelet and anticoagulant (APAC) agent on red blood cell deformability and aggregation in an experimental model.

Treatments with different antithrombotic agents can affect micro-rheological variables, such as red blood cell (RBC) deformability and aggregation. Since the effect of dual antiplatelet and anticoagulant (APAC) treatment on micro-rheology is unknown, we aimed to investigate the effect of different intravenous doses of APAC on hematological and micro-rheological variables in a porcine model. Two groups were formed (APAC group, Control group), and blood was collected from the animals at preset intervals. Hematological variables, RBC deformability, and aggregation were measured. We observed an improvement in the RBC deformability measured at a low shear stress range (< 3 Pa). However, after both doses, a decrease in the maximal elongation index of RBC values occurred in the APAC group. RBC aggregation increased after APAC bolus dose, while it gradually and dose-dependently decreased. Supposedly, the improvement in RBC deformability that was observed at a lower shear rate could facilitate aggregation. Administration of APAC and unfractionated heparin (UFH) caused comparable changes in hematological and hemorheological variables. Signs of thrombosis or bleeding did not occur. APAC and UFH had comparable micro-rheological effects.

Functional brain connectivity changes associated with day-to-day fluctuations in affective states.

Affective neuroscience has traditionally relied on cross-sectional studies to uncover the brain correlates of affects, emotions, and moods. Such findings obfuscate intraindividual variability that may reveal meaningful changing affect states. The few functional magnetic resonance imaging longitudinal studies that have linked changes in brain function to the ebbs and flows of affective states over time have mostly investigated a single individual. In this study, we explored how the functional connectivity of brain areas associated with affective processes can explain within-person fluctuations in self-reported positive and negative affects across several subjects. To do so, we leveraged the Day2day dataset that includes 40 to 50 resting-state functional magnetic resonance imaging scans along self-reported positive and negative affectivity from a sample of six healthy participants. Sparse multivariate mixed-effect linear models could explain 15% and 11% of the within-person variation in positive and negative affective states, respectively. Evaluation of these models' generalizability to new data demonstrated the ability to predict approximately 5% and 2% of positive and negative affect variation. The functional connectivity of limbic areas, such as the amygdala, hippocampus, and insula, appeared most important to explain the temporal dynamics of affects over days, weeks, and months.

An INSULIN and IAPP dual reporter enables tracking of functional maturation of stem cell-derived insulin producing cells.

OBJECTIVE: Human embryonic stem cell (hESC; SC)-derived pancreatic ß cells can be used to study diabetes pathologies and develop cell replacement therapies. Although current differentiation protocols yield SCß cells with varying degrees of maturation, these cells still differ from deceased donor human ß cells in several respects. We sought to develop a reporter cell line that could be used to dynamically track SCß cell functional maturation. METHODS: To monitor SCß cell maturation in vitro, we created an IAPP-2A-mScar and INSULIN-2A-EGFP dual fluorescent reporter (INS2A-EGFP/+;IAPP2A-mScarlet/+) hESC line using CRISPR/Cas9. Pluripotent SC were then differentiated using a 7-stage protocol to islet-like cells. Immunohistochemistry, flow cytometry, qPCR, GSIS and electrophysiology were used to characterise resulting cell populations. RESULTS: We observed robust expression of EGFP and mScarlet fluorescent proteins in insulin- and IAPP-expressing cells without any compromise to their differentiation. We show that the proportion of insulin-producing cells expressing IAPP increases over a 4-week maturation period, and that a subset of insulin-expressing cells remain IAPP-free. Compared to this IAPP-free population, we show these insulin- and IAPP-expressing cells are less polyhormonal, more glucose-sensitive, and exhibit decreased action potential firing in low (2.8 mM) glucose. CONCLUSIONS: The INS2A-EGFP/+;IAPP2A-mScarlet/+ hESC line provides a useful tool for tracking populations of maturing hESC-derived ß cells in vitro. This tool has already been shared with 3 groups and is freely available to all.

Ablation Parameters Predicting Pulmonary Vein Reconnection after Very High-Power Short-Duration Pulmonary Vein Isolation.

BACKGROUND: Recurrences due to discontinuity in ablation lines are substantial after pulmonary vein isolation (PVI) with radiofrequency ablation for atrial fibrillation. Data are scarce regarding the durability predictors for very high-power short-duration (vHPSD, 90 W/4 s) ablation. METHODS: A total of 20 patients were enrolled, who underwent 90 W PVI and a mandatory remapping procedure at 3 months. First-pass isolation (FPI) gaps, and acute pulmonary vein reconnection (PVR) sites were identified at the index procedure; and chronic PVR sites were identified at the repeated procedure. We analyzed parameters of ablation points (n = 1357), and evaluated their roles in predicting a composite endpoint of FPI gaps, acute and chronic PVR. RESULTS: In total, 45 initial ablation points corresponding to gaps in the ablation lines were analyzed. Parameters associated with gaps were interlesion distance (ILD), baseline generator impedance, mean current, total charge, and loss of catheter-tissue contact. The optimal ILD cut-off for predicting gaps was 3.5 mm anteriorly, and 4 mm posteriorly. CONCLUSIONS: Biophysical characteristics dependent on generator impedance could affect the efficacy of vHPSD PVI. The use of smaller ILDs is required for effective and durable PVI with vHPSD compared to the consensus targets with lower power ablation, and lower ILDs for anterior applications seem necessary compared to posterior points.

Solution NMR backbone resonance assignment of the full-length resistance-related calcium-binding protein Sorcin.

Sorcin is a penta-EF hand calcium-binding protein that confers multidrug resistance in cancer cells. It regulates cellular Ca2+ homeostasis by interacting with calcium channels such as Ryanodine receptor 2 and Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in a calcium-dependent manner. The crystal structure of the Sorcin has been determined in both calcium-free and calcium-bound states to understand calcium-binding induced conformational change. However, due to its flexibility, most of the N-terminal domain is invisible in these crystal structures. Here we report the 1H, 13C, and 15N backbone resonance assignments of full-length Sorcin in the calcium-free state using solution NMR. The protein secondary structure was predicted based on the assigned backbone chemical shifts using TALOS+ and CSI 3.0. Our backbone resonance assignment of the full-length Sorcin provides a foundation for future NMR spectroscopic studies to uncover the mechanism of Ca2+ sensing by Sorcin.

Mild Primary or Breakthrough SARS-CoV-2 Infection Promotes Autoantibody Production in Individuals with and without Neuro-PASC.

Patients with long COVID can develop humoral autoimmunity after severe acute SARS-CoV-2 infection. However, whether similar increases in autoantibody responses occur after mild infection and whether vaccination prior to SARS-CoV-2 breakthrough infection can limit autoantibody responses is unknown. In this study, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with rheumatic autoimmune diseases and diabetes in most individuals, regardless of vaccination status prior to infection. However, patients with long COVID and persistent neurologic and fatigue symptoms (neuro-PASC) have substantially higher autoantibody responses than convalescent control subjects at an average of 8 mo postinfection. Furthermore, high titers of systemic lupus erythematosus- and CNS-associated autoantibodies in patients with neuro-PASC are associated with impaired cognitive performance and greater symptom severity. In summary, we found that mild SARS-CoV-2 primary and breakthrough infections can induce persistent humoral autoimmunity in both patients with neuro-PASC and healthy COVID convalescents, suggesting that a reappraisal of mitigation strategies against SARS-CoV-2 is warranted to prevent transmission and potential development of autoimmunity.

Outcomes of Vacuum-Assisted Closure in Patients with Empyema Thoracis: A 10-Year Experience.

BACKGROUND: Video-assisted thoracic surgery is currently the recommended treatment for patients with empyema thoracis. However, open-window thoracostomy (OWT) is not uncommon and is performed as a last resort in patients who are in poor general condition or with complicated empyema. Although several professional associations have recommended vacuum-assisted closure (VAC) as an adjunct to standard treatment, exact data regarding the clinical role of intrathoracic VAC are not available. The primary objective of this study was to determine the safety and efficacy of intrathoracic VAC in debilitated patients and to compare the results with those of previous OWT studies. METHODS: We investigated 127 patients with a poor performance status who initially received inpatient intrathoracic VAC for stage II/III empyema thoracis between January 2010 and December 2020. RESULTS: The median duration of VAC was 15 days, and the median length of stay was 18 days. Two patients had complications, and the in-hospital mortality rate was 11.8% (15 of 127). Among the 112 surviving patients, 25 (22.3%) were discharged with OWT and 87 (77.7%) were discharged with a closed chest. Empyema recurred in 5 patients. Ultimately, we recorded an absolute success rate of 64.6% (82 of 127). CONCLUSIONS: Intrathoracic VAC appears to be safer and associated with less morbidity and mortality than OWT in debilitated patients with empyema. Our results revealed a reduced hospital length of stay and an improved success rate. The results of this work should contribute to improving treatment success in pleural empyema patients.

Failure of Surgical Aortic Valve Prostheses: An Analysis of Heart Team Decisions and Postoperative Outcomes.

Objectives: To analyze Heart Team decisions and outcomes following failure of surgical aortic valve replacement (SAVR) prostheses. Methods: Patients undergoing re-operations following index SAVR (Redo-SAVR) and those undergoing valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) following SAVR were included in this study. Patients who underwent index SAVR and/or Redo-SAVR for endocarditis were excluded. Data are presented as medians and 25th-75th percentiles, or absolute numbers and percentages. Outcomes were analyzed in accordance to the VARC-3 criteria. Results: Between 01/2015 and 03/2021, 53 patients underwent Redo-SAVR, 103 patients ViV-TAVR. Mean EuroSCORE II was 5.7% (3.5-8.5) in the Redo-SAVR group and 9.2% (5.4-13.6) in the ViV group. In the Redo-SAVR group, 12 patients received aortic root enlargement (22.6%). Length of hospital and ICU stay was longer in the Redo-SAVR group (p < 0.001; p < 0.001), PGmax and PGmean were lower in the Redo-SAVR group as compared to the ViV-TAVR group (18 mmHg (10-30) vs. 26 mmHg (19-38), p < 0.001) (9 mmHg (6-15) vs. 15 mmHg (9-21), p < 0.001). A higher rate of paravalvular leakage was seen in the ViV-TAVR group (p = 0.013). VARC-3 Early Safety were comparable between the two populations (p = 0.343). Survival at 1 year and 5 years was 82% and 36% in the ViV-TAVR cohort and 84% and 77% in the Redo-SAVR cohort. The variables were patient age (OR 1.061; [95% CI 1.020-1.104], p = 0.004), coronary heart disease (OR 2.648; [95% CI 1.160-6.048], p = 0.021), and chronic renal insufficiency (OR 2.711; [95% CI 1.160-6.048], p = 0.021) showed a significant correlation to ViV-TAVR. Conclusions: Heart Team decisions are crucial in the treatment of patients with degenerated aortic bioprostheses and lead to a low mortality in both treatment paths thanks to patient-specific therapy planning. ViV-TAVR offers a treatment for elderly or intermediate-risk profile patients with comparable short-term mortality. However, this therapy is associated with increased pressure gradients and a high prevalence of paravalvular leakage. Redo-SAVR enables the surgical treatment of concomitant cardiac pathologies and allows anticipation for later VIV-TAVR by implanting the largest possible valve prostheses.

Multi-shank 1024 channels active SiNAPS probe for large multi-regional topographical electrophysiological mapping of neural dynamics.

Implantable active dense CMOS neural probes unlock the possibility of spatiotemporally resolving the activity of hundreds of single neurons in multiple brain circuits to investigate brain dynamics. Mapping neural dynamics in brain circuits with anatomical structures spanning several millimeters, however, remains challenging. Here, we demonstrate the first CMOS neural probe for mapping intracortical neural dynamics (both LFPs and spikes) in awake, behaving mice from an area >4 mm2. By taking advantage of the modularity of our SiNAPS technology, we realized an eight shanks probe with 1024 electrode channels arranged on each shank in regular arrays with an electrode pitch <30 µm. Low-noise recordings from all electrodes at 20 kHz/channel demonstrate a field of view spanning the 2D lattice of the entire mice hippocampal circuit, together with cortical and thalamic regions. This arrangement allows combining large population unit recording across distributed networks with precise intra- and interlaminar/nuclear mapping of the oscillatory dynamics.

Radical chain mechanism for the S2O8 2--S2O3 2--Cu(ii) flow system explains high-amplitude pH oscillations in the NH4OH-modified version.

Peroxodisulfate is well known as an important reagent in analytical, environmental and other branches of chemistry, as well as in industrial processes. One of the most studied oxidative reactions peroxodisulfate participates in as an oxidizer is the Cu(ii)-catalyzed peroxodisulfate-thiosulfate reaction. When carried out in a flow reactor, this system shows oscillatory dynamics characterized by periodic changes in the Pt-potential and [O2] while it only displays variation in the pH with a few tenths of unit magnitude. Our recent experiments unveiled an increase of the amplitude of the pH oscillations that exceeds 4 units when NH4OH was introduced into the oscillatory flow system. The dynamics of Cu(ii)-catalyzed peroxodisulfate-thiosulfate reaction has been described in detail but the chemical mechanism explaining the oscillatory behavior has not been established. Based on what is known about the uncatalyzed reaction between peroxodisulfate and thiosulfate in the literature, we have developed a mechanism that includes radical chain reactions which can explain the oscillatory phenomena. The proposed mechanism includes 13 reactions with the radical ions SO4˙-, S2O3˙-, S2O8˙-, OH˙ and two acid-base equilibria, including the dissociation equilibrium of NH4OH accounting for its effect on the amplitude of pH oscillations. Using this model, we successfully simulated the behavior of this system: (1) the evolution of the concentrations of the initial reagents, radicals, and catalyst over time in batch configuration, (2) the periodic changes in the concentrations of radicals and the oxidized and reduced forms of the catalyst, pH and [O2] in flow conditions. Our model also explains the amplification of the pH cycles without impacting the redox processes when NH4OH is added, which is a novel phenomenon observed in nonlinear chemical reactions. The high amplitude pH oscillations we report in the peroxodisulfate-thiosulfate-Cu(ii)-NH4OH flow reaction may enable future applications where this system may serve (a) as a core oscillator in coupled chemical systems, or (b) as a pH oscillator capable of running in a closed reactor configuration.

No Significant Beneficial Effects of Intravenous N-Acetylcysteine on Patient Outcome in Non-Paracetamol Acute Liver Failure: A Meta-Analysis of Randomized Controlled Trials.

Acute liver failure is a life-threatening organ dysfunction with systemic organ involvement and is associated with significant mortality and morbidity unless specific management is undertaken. This meta-analysis aimed to assess the effects of intravenous N-acetylcysteine (NAC) on mortality and the length of hospital stay in patients with non-acetaminophen acute liver failure. Two hundred sixty-six studies from four databases were screened, and four randomized control trials were included in the final analysis. Our results could not demonstrate increased overall survival (OR 0.70, 95% CI [0.34, 1.44], p = 0.33) or transplant-free survival (OR 0.90, 95% CI [0.25, 3.28], p = 0.87) in patients treated with intravenous NAC. We observed an increased overall survival in adult patients treated with NAC (OR 0.59, 95% CI [0.35, 0.99], p = 0.05) compared to pediatric patients, but whether this is attributed to the age group or higher intravenous dose administered remains unclear. We did not observe a decreased length of stay in NAC-treated patients (OR -5.70, 95% CI [-12.44, 1.05], p = 0.10). In conclusion, our meta-analysis could not demonstrate any significant benefits on overall and transplant-free patient survival in non-acetaminophen ALF. Future research should also focus on specific etiologies of ALF that may benefit most from the use of NAC.