Time Research Articles

Efficacy of Neoadjuvant Radiotherapy After Chemotherapy and the Optimal Interval from Radiotherapy to Surgery for Borderline Resectable and Resectable Pancreatic Cancer.

Benefits of neoadjuvant treatment for pancreatic cancer with major vessel invasion has been demonstrated through randomized controlled trials; however, the optimal neoadjuvant treatment strategy remains controversial, especially for radiotherapy. Therefore, we aimed to evaluate the efficacy and safety of neoadjuvant radiotherapy followed by chemotherapy and the optimal time interval to undergo surgery after radiotherapy in (borderline) resectable pancreatic cancer. Between 2013 and 2022, patients with (borderline) resectable pancreatic cancer with vessel contact who received 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan or gemcitabine and nanoparticle albumin-bound paclitaxel as initial treatment following surgery were included. Patients who received radiotherapy after chemotherapy and those who did not were matched using 1:1 nearest-neighbor propensity scores. Propensity scores were measured using the tumor size at initial image, duration of neoadjuvant chemotherapy, and responsiveness to neoadjuvant chemotherapy. Of 212 patients, 166 patients were retrieved for the matched cohort. Patients who received radiotherapy had significantly better postoperative survival, local control, and R0 resection rates than those who did not. Furthermore, patients who underwent surgery within 4 weeks after completing radiotherapy had lower intraoperative blood loss and a clinically relevant postoperative pancreatic fistula rate than those who underwent surgery after more than 4 weeks. In patients with (borderline) resectable pancreatic cancer with vessel contact who were scheduled for curative-intent surgery after neoadjuvant chemotherapy, additional radiotherapy was associated with better postoperative survival and local control. Furthermore, our findings suggested that scheduling surgery within 4 weeks following radiation therapy might enhance the perioperative outcomes.

Pseudo-energy-preserving explicit Runge-Kutta methods

Using a recent characterization of energy-preserving B-series, we derive the explicit conditions on the coefficients of a Runge-Kutta method that ensure energy preservation (for Hamiltonian systems) up to a given order in the step size, which we refer to as the pseudo-energy-preserving (PEP) order. We study explicit Runge-Kutta methods with PEP order higher than their classical order. We provide examples of such methods up to PEP order six, and test them on Hamiltonian ODE and PDE systems. We find that these methods behave similarly to exactly energy-conservative methods over moderate time intervals and exhibit significantly smaller errors, relative to other Runge-Kutta methods of the same order, for moderately long-time simulations.

The Influence of Electroencephalographic Density Spectral Array Guidance of Sevoflurane Administration on Recovery From General Anesthesia in Children. A Randomized Controlled Trial.

In children, monitoring depth of anesthesia is challenging because of the still developing brain. Electroencephalographic density spectral array monitoring provides age- and anesthetic drug-specific electroencephalographic patterns, making it suitable for use in children. Yet, not much is known about the benefits of using density spectral array on post-operative recovery in children. In this randomized controlled trial, the primary aim was to investigate the influence of density spectral array monitoring during general anesthesia on the speed of recovery after surgery. Children aged 6 months-12 years scheduled for elective surgery under general anesthesia supplemented with caudal analgesia had either sevoflurane anesthesia titrated to maintain a characteristic density spectral array pattern or based on a predefined end-tidal sevoflurane concentration of 2.3% (standard care group). The time interval between the discontinuation of sevoflurane and the moment when discharge criteria from the operating room were met (Steward score of 3 or more) was defined as the primary outcome parameter of this trial. Data from 96 children were analyzed. The time until discharge readiness from the operating room was shorter in group density spectral array (6 min. [13[4-16.8]]) than in group standard care (12 min. [18[6-24.3]]), with a difference between medians of 6 min (95% CI -7 to 0), p = 0.041. The mean end-tidal sevoflurane concentration during the surgical procedure was lower in group density spectral array, 1.8% (0.34) versus 2.3% (0.1) in group standard care (95% CI 0.4-0.7), p < 0.001. This randomized controlled trial provides initial evidence of an added value of density spectral array monitoring in terms of the speed of recovery and allows sevoflurane to be dosed 22% lower during maintenance than with a more traditional approach using a minimal alveolar concentration of 0.9. ClinicalTrials.gov identifier: NCT05525104.

Interrupted time series analysis to evaluate the impact of COVID-19-pandemic on the incidence of notifiable infectious diseases in the Lazio region, Italy

BackgroundThe coronavirus disease 2019 (COVID-19) emergency has represented a profound upheaval in the dynamics of infectious diseases transmission worldwide. This phenomenon has been at least in part driven by the introduction of non-pharmaceutical interventions (NPIs), implemented to counteract viral transmission. Our study aimed to assess the magnitude and the features of the impact of the COVID-19 pandemic on the incidence of notifiable infectious diseases (NIDs) in the Lazio region, Italy.MethodsData on NIDs in the Lazio Region with symptom onset date included in the time interval from 1 January 2017 to 31 December 2023 were collected from different surveillance system databases available at SERESMI/Lazio Region Unit and classified into five categories based on the main transmission route of the disease. Descriptive statistics were performed and interrupted time series (ITS) analysis was used to assess the effect of the COVID-19 pandemic and subsequent recovery period on monthly NIDs cases.ResultsImmediately after the start of the COVID-19 pandemic, a significant, sharp and immediate reduction in monthly cases was recorded for all NIDs (-86.73%), regardless of the transmission route. The decrease was particularly significant for vector-borne, food-borne and respiratory-transmitted diseases (RDs), and in general in females.During the COVID-19 recovery phase, monthly cases of all NIDs showed a significant positive level change, particularly significant for sexually transmitted/blood-borne diseases, contact diseases and RDs.DiscussionThe COVID-19 pandemic has been responsible for the disruption of all NIDs transmission patterns, while the magnitude and dynamics of its effects varied depending on the transmission route; furthermore, the impact of the pandemic wave was still noticeable during the post-COVID-19 era and the incidence trajectories of NIDs in this phase were peculiar for each disease category.

Impact of workflow times on successful reperfusion after endovascular treatment in the late time window.

Successful and complete reperfusion should be the aim of every endovascular thrombectomy (EVT) procedure. However, the effect of time delays on successful reperfusion in late window stroke patients presenting 6-to-24h from onset has not been investigated. We pooled individual patient-level data from seven trials and registries for anterior circulation stroke patients treated with EVT between 6 and 24h from onset. We explored the impact of delays across multiple interval times, including onset to hospital arrival; hospital arrival to arterial puncture; imaging to arterial puncture; and onset to arterial puncture. Our primary outcome was successful reperfusion, defined as a modified thrombolysis in cerebral infarction (mTICI) score of 2b-3. Logistic regression analyses were performed to assess the association between each of the interval times and successful reperfusion. We included 608 patients. The median age was 70years (IQR 58-79), and 307 (50.5%) were females. Successful reperfusion was achieved in 494 (81.2%) patients. Patients with successful reperfusion had lower NIHSS scores (median 15 [IQR11-19] vs 17 [11-21], p = .02) and significantly shorter hospital arrival to arterial puncture time (90min [60-150] vs 110min [84.5-150], p = .01) than unsuccessful reperfusion. The odds of successful reperfusion decreased by 15% for every one-hour delay in arrival-to-puncture time (adjusted odds ratio 0.85, 95% CI: 0.75-0.95). Other workflow times did not impact the rate of successful reperfusion. Faster hospital arrival to arterial puncture time is associated with higher odds of successful reperfusion in late window stroke patients.

Improved plant biomass production under low nitrogen conditions through conditional accumulation of the second messenger, guanosine tetraphosphate, in chloroplasts and mitochondria.

To enhance plant biomass production under low nitrogen conditions, we employed a method to artificially and temporarily accumulate the bacterial second messenger, guanosine tetraphosphate (ppGpp), to modify plastidial or mitochondrial metabolism. Specifically, we fused a chloroplast or mitochondrial transit-peptide to the N-terminus of the bacterial ppGpp synthase YjbM, which was conditionally expressed by an estrogen-inducible promoter in Arabidopsis. The resulting recombinant Arabidopsis plants exhibited estrogen-dependent ppGpp accumulation in chloroplasts or mitochondria and showed reduced fresh weight compared to wild type (WT) plants when grown on agar-solidified plates containing a certain amount of estrogen. This finding aligns with the previous study indicating that plastidial ppGpp levels can influence plant biomass production. When the recombinant plants were grown in the soil with estrogen and low nitrogen-containing water at specific time intervals, they exhibited greater fresh weight than WT plants. These results suggest that the conditional accumulation of ppGpp in not only chloroplasts, but also in mitochondria can lead to improved plant biomass production in soil with low nitrogen applications.

Recent progress in tsunami deposit investigations in Taiwan

Abstract Identifying deposits of modern/historical and prehistorical tsunamis in Taiwan has been successful in the past two decades and has substantially increased the extant tsunami catalogs, which have been limited in the past four centuries due to scarce and ambiguous historical accounts. In this review, the initiation of the investigation is briefly discussed, partly in response to the latest catastrophic tsunamis in the Indo-Pacific and the stimulated public concern in Taiwan. Major developments and results of the investigation include the onset of the first stage before 2010, with findings in Keelung, the eastern coast, and Lanyu Island, and the second/ongoing stage after 2013, with findings in the northern and eastern coasts and Penghu Islands. These findings contributed to validating the debated historical events, expanding the event number and time span of the tsunami catalog, and elaborating on tsunami processes, which collectively enabled the delineation of the recurrence time intervals between events. Limitations, uncertainty, further contributions, and feedback are discussed including insights into the regional western Pacific hazards of tsunamis, earthquakes, and volcanic eruptions; the principles of recognizing tsunami deposits and processes; and the propositions of future studies and hazard mitigations in Taiwan.

Changes in life satisfaction over six years in the general population: A longitudinal study with the Satisfaction With Life Scale (SWLS).

Satisfaction with life is a key concept for most individuals. The Satisfaction With Life Scale (SWLS) for measuring general life satisfaction has been widely analyzed in terms of cross-sectional associations. However, the knowledge about long-term changes in life satisfaction and the associations between such changes and changes in other variables of physical and mental health is limited. A community-based representative sample of the general population has been examined twice with a time interval of six years (n = 4,999), using the SWLS and several other scales. Over the six years, the mean SWLS score of the total sample remained nearly unchanged (M = 27.0, SD = 5.2, both at t1 and at t2). The test-retest correlation was rtt = 0.66 for the total sample, and there were only marginal differences in temporal stability between male and female respondents. Changes in the SWLS over the six years were correlated with changes in optimism (r = 0.23), mental health (r = 0.26), social functioning (r = 0.22), perceived social support (r = 0.21), anxiety (r = -0.30), and physical complaints (r = -0.18). These change score correlations were lower than the corresponding coefficients under the cross-sectional perspective. Measurement invariance across sex, age, and time was established. The SWLS proved to be an appropriate tool for assessing changes in life satisfaction, and correlations between change scores of life satisfaction and health-related variables complement the knowledge about these associations from a cross-sectional perspective.

Manipulation of Richtmyer–Meshkov instability on a heavy–light interface via successive shocks

The manipulation of the Richtmyer–Meshkov instability growth at a heavy–light interface via successive shocks is theoretically analysed and experimentally realized in a specific shock-tube facility. An analytical model is developed to forecast the interface evolution before and after the second shock impact, and the possibilities for the amplitude evolution pattern are systematically discussed. Based on the model, the parameter conditions for each scenario are designed, and all possibilities are experimentally realized by altering the time interval between two shock impacts. These findings may enhance the understanding of how successive shocks influence hydrodynamic instabilities in practical applications.

Contrastive learning with transformer for adverse endpoint prediction in patients on DAPT post-coronary stent implantation.

Effective management of dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation is crucial for preventing adverse events. Traditional prognostic tools, such as rule-based methods or Cox regression, despite their widespread use and ease, tend to yield moderate predictive accuracy within predetermined timeframes. This study introduces a new contrastive learning-based approach to enhance prediction efficacy over multiple time intervals. We utilized retrospective, real-world data from the OneFlorida + Clinical Research Consortium. Our study focused on two primary endpoints: ischemic and bleeding events, with prediction windows of 1, 2, 3, 6, and 12 months post-DES implantation. Our approach first utilized an auto-encoder to compress patient features into a more manageable, condensed representation. Following this, we integrated a Transformer architecture with multi-head attention mechanisms to focus on and amplify the most salient features, optimizing the representation for better predictive accuracy. Then, we applied contrastive learning to enable the model to further refine its predictive capabilities by maximizing intra-class similarities and distinguishing inter-class differences. Meanwhile, the model was holistically optimized using multiple loss functions, to ensure the predicted results closely align with the ground-truth values from various perspectives. We benchmarked model performance against three cutting-edge deep learning-based survival models, i.e., DeepSurv, DeepHit, and SurvTrace. The final cohort comprised 19,713 adult patients who underwent DES implantation with more than 1 month of records after coronary stenting. Our approach demonstrated superior predictive performance for both ischemic and bleeding events across prediction windows of 1, 2, 3, 6, and 12 months, with time-dependent concordance (Ctd) index values ranging from 0.88 to 0.80 and 0.82 to 0.77, respectively. It consistently outperformed the baseline models, including DeepSurv, DeepHit, and SurvTrace, with statistically significant improvement in the Ctd-index values for most evaluated scenarios. The robust performance of our contrastive learning-based model underscores its potential to enhance DAPT management significantly. By delivering precise predictive insights at multiple time points, our method meets the current need for adaptive, personalized therapeutic strategies in cardiology, thereby offering substantial value in improving patient outcomes.

Smart Zinc-Based Coatings with Chitosan–Alginate Nanocontainers Loaded with ZnO and Caffeine for Corrosion Protection of Mild Steel

The development of environmentally friendly materials is a subject of increasing interest in corrosion protection research. The objective of the present investigation is to propose the preparation procedure of chitosan–alginate (CHI/ALG) nanocontainers loaded with zinc oxide (ZnO) nanoparticles or combining ZnO nanoparticles with corrosion inhibitor caffeine (CAF), both suitable for incorporation into the matrix of ordinary zinc coatings on mild steel substrates. The nanocontainers were synthesized through spontaneous polysaccharide complexation in the presence of ZnO nanoparticles and CAF using a cross-linking agent, namely tripolyphosphate (TPP). Dynamic light scattering and laser Doppler velocimetry measurements are used for evaluation of the size distribution and zeta potentials of the nanocontainers, both loaded or unloaded with CAF. Using UV-spectroscopy, entrapment efficiency and release amounts of CAF are quantitatively evaluated. The nanocontainers thus obtained were incorporated into the matrices of ordinary zinc coatings via co-electrodeposition with zinc from zinc sulfate solution, aiming to improve the corrosion protection of steel in corrosive environments containing chloride ions. The surface morphology and elemental composition of the electrodeposited hybrid coatings before and after treating in the model corrosive medium of 3.5% NaCl is studied by scanning electron microscopy (SEM). The cyclic voltammetry method (CVA) is applied to characterize the cathodic (electrodeposition) and anodic (dissolution) processes. The protective characteristics of the hybrid coatings are investigated by application of potentiodynamic polarization (PDP) curves and polarization resistance (Rp) measurements after a time interval of 40 days. The obtained results indicate that both hybrid coating types could prolong the life time of mild steel in aggressive Cl− ion-containing solution, combining the protection effect of sacrificial zinc with barrier (ZnO) and active (CAF) protective effects.

Accelerated Modeling of Transients in Electromagnetic Devices Based on Magnetoelectric Substitution Circuits

During switching in electrical systems, transient electromagnetic processes occur. The resulting dangerous current surges are best studied by computer simulation. However, the time required for computer simulation of such processes is significant for complex electromagnetic devices, which is undesirable. The use of spectral methods can significantly speed up the calculation of transient processes and ensure high accuracy. At present, we are not aware of publications showing the use of spectral methods for calculating transient processes in electromagnetic devices containing ferromagnetic cores. The purpose of the work: The objective of this work is to develop a highly effective method for calculating electromagnetic transient processes in a coil with a ferromagnetic magnetic core connected to a voltage source. The method involves the use of nonlinear magnetoelectric substitution circuits for electromagnetic devices and a spectral method for representing solution functions using orthogonal polynomials. Additionally, a schematic model for applying the spectral method is developed. Obtained Results: A method for calculating transients in magnetoelectric circuits based on approximating solution functions with algebraic orthogonal polynomial series is proposed and studied. This helps to transform integro-differential state equations into linear algebraic equations for the representations of the solution functions. The developed schematic model simplifies the use of the calculation method. Representations of true electric and magnetic current functions are interpreted as direct currents in the proposed substitution circuit. Based on these methods, a computer program is created to simulate transient processes in a magnetoelectric circuit. Comparing the application of various polynomials enables the selection of the optimal polynomial type. The proposed method has advantages over other known methods. These advantages include reducing the simulation time for electromagnetic transient processes (in the examples considered, by more than 12 times than calculations using the implicit Euler method) while ensuring the same level of accuracy. The simulation of processes over a long time interval demonstrate error reduction and stabilization. This indicates the potential of the proposed method for simulating processes in more complex electromagnetic devices, (for example, transformers).

The impact of combination of zofenopril and different diuretics on regression of myocardial reperfusion injury and oxidative status in spontaneously hypertensive rats.

As several decades of research have shown the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors alone or in combination with diuretics, we were interested in investigating the effects of subchronic therapy of these drugs on ischemia-reperfusion (I/R) damage to the heart, as well as their influence on oxidative status. The research was conducted on 40 spontaneously hypertensive male Wistar Kyoto rats, divided into 4 groups. Animals were treated for four weeks with 10mg/kg/day zofenopril alone or in combination with hydrochlorothiazide, indapamide and spironolactone per os. After the treatment, hemodynamic measurements, echocardiography and assessment of myocardial function were performed according to Langendorff's retrograde perfusion method. The induced global ischemia model involved 20min of ischemia followed by 30min of reperfusion to the heart (I20:R30). Markers of oxidative stress were determined spectrophotometrically from plasma and erythrocyte lysates. Heart and kidney tissue samples were pathohistologically analyzed. Treatment with a combination of ACE inhibitors and diuretics significantly lowered blood pressure in spontaneously hypertensive rats, alleviated left ventricular hypertrophy and increased ejection fraction. On the other hand, treatment with zofenopril and diuretics showed pro-oxidative potential. Pathohistological analysis of heart and kidney tissue samples indicates that subchronic administration of antihypertensive agents does not lead to significant changes in these organs. Since the antihypertensive therapy was relatively short (only 4weeks), in order to elucidate or deny the prooxidative mechanism, additional studies of a longer time interval are needed and planned.

Optimizing the Design of a Lateral Oscillating Device for Pressure Ulcer Prevention: Results of a Quasi-experimental Study.

The aim of this study was to propose a lateral oscillating device for the prevention of pressure ulcers by understanding the mechanisms of tissue protection in healthy individuals during prolonged decubitus. We also sought to determine the optimal time interval for oscillation, considering peak pressure peaks and tolerable pressure limits as a function of individual characteristics such as age, weight, height, gender, and BMI. A quasi-experimental, descriptive and analytical observational study was conducted between January 2022 and June 2023 with a sample of 25 healthy volunteers. Sacral, heel and trochanter pressure measurements were performed using sensors. Descriptive and bivariate statistical analyses were applied, and a linear regression model was used to analyze the relationship between independent variables and peak pressures recorded. Peak pressure at the trochanter was significantly associated with age, weight and gender, while pressure at the sacrum showed a relationship only with gender. No significant associations were found for other variables. The 80th percentile was used to determine the maximum tolerable pressure, and the independent variables collectively explained 60% of the variance in maximum trochanter pressure (R2 = 0.60; p = 0.0006). These findings helped to establish optimal time intervals for lateral oscillation, tailored to individual variability. The designed lateral oscillating device proved to be effective in promoting tissue perfusion and reducing pressure build-up, thus contributing to pressure ulcer prevention. This personalized approach could significantly improve the care of immobilized patients in clinical settings.

The efficacy of ultrasound-assisted pterygopalatine blockade by the posterior-anterior infrazygomatic approach during eye enucleation: prospective randomized comparative study

BACKGROUND: The pterygopalatine blockade (PPB) has broad indications in ophthalmology, which explains the possibility of simultaneous influence on sympathetic, parasympathetic and nociceptive innervation. Ultrasound navigation is widely used to control blockades, but currently there is no information on the clinical efficacy of performing ultrasound-assisted pterygopalatine blockade with different access. OBJECTIVE: Our aim was to compare the efficacy of performing ultrasound-navigated PPB with by posterior-anterior infrazygomatic and supra-zygomatic approaches in patients after eye enucleation. MATERIALS AND METHODS: A prospective randomized study was conducted. For postoperative anesthesia in group 1 PPB was performed using a posterior-anterior infrazygomatic approach (n=30), in group 2 (n=30) — using a supra-zygomatic approach. The time of PPB performance, the anesthesia start time, changes in blood pressure and heart rate as well as technical features of the blockade were evaluated. RESULTS: A comparison of the time interval from the blockade performance to the anesthesia start time in the groups demonstarted that in patients of group 1 it was 5.3±1.0min., which had significant differences with the results in group 2 — 10.1±1.4min. (p=0.041). When comparing the dynamics of the onset of the analgesic effect, the PPB demonstrated that in patients of group 1, the time for the onset of anesthesia was 5.3±1.0min., compared with the results of group 2 — 10.1±1.4min. (p=0.041). A statistically significant difference was found in the time of onset of a skin sensitivity decrease in the suborbital region and the time required for a pain syndrome relief: in group 1 — 8.9±0.9min. and 13.5±0.7min., in group 2 — 14.4 ±1.2min. and 19.6±1.7min., respectively (p=0.037, p=0.034). The PPB values in patients of group 1 were 91.2±6.5mmHg significantly lower compared with the values of patients of group 2 — 101.1±6.6mmHg, respectively (p=0.001). When performing PPB by the supra-zygomatic approach (group 2), in 53.3% (n=16) of cases patients reacted to painful sensations, the average score for PPB was 2.3±0.5. CONCLUSION: In the treatment of pain syndrome after enucleation of the eye, the method of choice is ultrasound-assisted PPB blockade by the posterior-anterior infrazygomatic approach, which, in comparison with the blockade by the supra-zygomatic approach, ensures the rapid start of effective analgesia, comfort and safety for the patient.

Time Perception Test in IntelliCage System for Preclinical Study: Linking Depression and Serotonergic Modulation.

Background/Objectives:: The link between serotonergic modulation and depression is under debate; however, serotonin reuptake inhibitors (SRIs) are still the first-choice medicine in this condition. Disturbances in time perception are also reported in depression with one of the behavioral schedules used to study interval timing, differential-reinforcement-learning-of-low-rate, having been shown to have high predictive validity for an antidepressant effect. Here, we introduce an IntelliCage research protocol of an interval bisection task that allows more ecologically valid and less time-consuming rodent examination and provides an example of its use to confirm the previously reported acute effect of an SRI, clomipramine, on interval timing (increase in bisection point, D50). Methods: Wistar male rats (n = 25, five groups of 5-8) were trained in the IntelliCage to discriminate between short (1 s) and long (4 s) LED light stimuli by nose poking at the corresponding (left/right) side of the IntelliCage chamber to obtain a drink. When 80% of correct responses were reached, the intermediate durations of 1.7, 2.5, and 3.3 s were introduced. The number of left/right choices for each stimulus and interval timing parameters (bisection point, D50, and timing precision), derived from them, were compared after saline and clomipramine (7 mg/kg, i.p) intraperitoneal administration. Results: Rats successfully learned the task within about a week of training. The slightly increased D50 after clomipramine confirmed previous studies. Conclusions: The introduced protocol has potential to be applicable to preclinical research on depression and potentially other psychopathology, where time perception can be disturbed.

Azimuthal metallicity variations, spiral structure, and the failure of radial actions based on assuming axisymmetry

ABSTRACT We study azimuthal variations in the mean stellar metallicity, $\langle {\rm{[Fe/H]}}\rangle $, in a self-consistent, isolated simulation in which all stars form out of gas. We find $\langle {\rm{[Fe/H]}}\rangle$ variations comparable to those observed in the Milky Way and which are coincident with the spiral density waves. The azimuthal variations are present in young and old stars and therefore are not a result of recently formed stars. Similar variations are present in the mean age and $\rm \alpha$-abundance. We measure the pattern speeds of the $\langle {\rm{[Fe/H]}}\rangle$-variations and find that they match those of the spirals, indicating that spirals are the cause of the metallicity patterns. Because younger stellar populations are not just more $\rm [Fe/H]$-rich and $\rm \alpha$-poor but also dynamically cooler, we expect them to more strongly support spirals, which is indeed the case in the simulation. However, if we measure the radial action, $J_{R}$, using the Stäckel axisymmetric approximation, we find that the spiral ridges are traced by regions of high $J_{R}$, contrary to expectations. Assuming that the passage of stars through the spirals leads to unphysical variations in the measured $J_{R}$, we obtain an improved estimate of $J_{R}$ by averaging over a $1\rm{\:{Gyr}}$ time interval. This time-averaged $J_{R}$ is a much better tracer of the spiral structure, with minima at the spiral ridges. We conclude that the errors incurred by the axisymmetric approximation introduce correlated deviations large enough to render the instantaneous radial actions inadequate for tracing spirals.

Adiposity-related anthropometric parameters, indoles and atherosclerotic cardiovascular disease in Chinese adults: a prospective cohort study

Objective: To investigate the relationship of several adiposity-related anthropometric parameters, including BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP) and indoles in plasma with the incidence of atherosclerotic cardiovascular disease (ASCVD) in adults in China. Methods: In China Kadoorie Biobank (CKB) study, blood samples were collected from 2 183 participants in the first resurvey in 2008 to detect indoles. Participants' body weight, body height, WC, hip circumference, and BFP were measured at baseline survey in 2004 and resurvey in 2008, the BMI and WHR were calculated with standardized methods. The long-term follow-up of all participants started from the completion of the resurvey in 2008 until the occurrence of incident ASCVD, death, loss to follow-up or until December 31, 2018. CKB ascertained outcome status (incident ASCVD) through death and disease registries and national health insurance databases, supplemented by active follow-up. Multivariate linear regression model was used to estimate the associations of anthropometric measurements at baseline survey and the first resurvey, and changes in these measurements with 3 indoles [indole, indole-3-acetic acid (IAA), and indole-3-propionic acid (IPA)]. Cox proportional hazard regression model was used to estimate the associations between indoles and the risk for ASCVD. Results: Anthropometric measurements at baseline survey or the first resurvey were negatively associated with plasma IPA level. The regression coefficient (β) of baseline BMI (per 1.0 kg/m2) with 0.1 standard deviation (SD) IPA was -0.23 (95%CI: -0.36 - -0.10) (false discovery rate=0.004). After adjusting for baseline BMI, the β of baseline WC, WHR and BFP with 0.1 SD IPA were -0.09 (95%CI: -0.18 - -0.01), -0.12 (95%CI: -0.19 - -0.05), and -0.20 (95%CI: -0.32 - -0.08), respectively. The annual change in BMI (difference between BMI in 2008 and 2004 divided by the time interval) was associated with indole and IAA, with β of 1.40 (95%CI: 0.58 - 2.21) and -1.07 (95%CI: -1.91 - -0.23), respectively, at each 0.1 increase of SD. Over a median (Q1, Q3) follow-up of 10.46 (10.36, 10.53) years after 2008 resurvey, 236 cases of ASCVD were recorded. IAA and IPA levels were negatively associated with the risk for ASCVD, with hazard ratios for one SD increase of IAA and IPA of 0.87 (95%CI: 0.76 - 0.99) and 0.84 (95%CI: 0.73 - 0.96), respectively. Conclusions: Our results suggested that anthropometric measurements and their changing trends affect the levels of plasma imicrobial tryptophan metabolite levels, decreased levels of IAA and IPA levels are associated with increased risk of ASCVD and indoles in plasma including IPA and IAA might be the mediating factors for adiposity-induced ASCVD.

Prospective Multicenter Evaluation of the MDS "Suggestive of PSP" Diagnostic Criteria.

The recent Movement Disorders Society (MDS)-progressive supranuclear palsy (PSP) diagnostic criteria conceptualized three clinical diagnostic certainty levels: "suggestive of PSP" for sensitive early diagnosis based on subtle clinical signs, "possible PSP" balancing sensitivity and specificity, and "probable PSP" highly specific for PSP pathology. The aim of this study was to prospectively validate the criteria against long-term clinical follow-up and characterize the diagnostic certainty increase over time. Patients with "possible PSP" or "suggestive of PSP" diagnosis and clinical follow-up were recruited in two German multicenter longitudinal observational studies (ProPSP and DescribePSP). The cumulative percentage of patients longitudinally increasing diagnostic certainty was assessed over up to 2.5 years of follow-up. The sample size per arm required to detect 30% attenuated rate in diagnostic certainty increase in trials was estimated over multiple time intervals. Of 254 patients with available longitudinal data, 61 patients had low diagnostic certainty at baseline (48 suggestive of PSP, 13 possible PSP) and multiple clinical visits (median: 3, range: 2-4). The cumulative percentage of patients increasing diagnostic certainty progressed with follow-up duration (30.4% at 6 months, 51.7% at 1 year, 80.4% at 2.5 years). The sample size required to detect 30% reduction in diagnostic certainty increase rate within 1 year was 163, slightly smaller than that required using the PSP rating scale. Most "suggestive of PSP" patients increased diagnostic certainty upon longitudinal follow-up, providing the first prospective multicenter validation of MDS-PSP diagnostic criteria. Our data support the design of trials tailored for these early-stage patients, suggesting the PSP rating scale and the diagnostic certainty increase rate as potential endpoint measures. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Serum interleukin-6 and associated nociceptive parameters following subcutaneous infiltration of lidocaine alone, tramadol alone, and their combination in red Sokoto goat undergoing rumenotomy

The clinical practice of combining one or more drugs is gaining attention for enhancing efficacy, leading to quicker onset of action, longer duration of effect and minimising side effects. Previous studies showed that combining lignocaine and tramadol in an epidural injection significantly extended the duration of analgesia produced when compared to the use of lignocaine alone. The significance of this study is aiming toward improved pain management during surgery, especially in goats. In this study, the analgesic effects of subcutaneously administered lignocaine alone (7 mgkg-1), tramadol alone (3 mgkg-1), and their respective combination of 3.5 and 15 mgkg-1 on pain in goats undergoing rumenotomy were compared. The experiment was carried out on fifteen healthy (N=15) Red Sokoto goats. Blood was drawn from the jugular vein at seven distinct time intervals during the course of the experiment (0, 1, 2, 3, 4, 5, 6 and 7 hours) and serum was extracted. The severity of pain was ascertained by measuring serum level of IL-6 and the nociceptive response to a pain stimulus using a clinical algometer. This study revealed that the combination of lidocaine (03.78 minutes) and tramadol (3.68 minutes) has a quicker onset of action (2.01±0.42 minutes) and a more extended duration of activity (79.5 minutes) when compared to lidocaine (60 minutes) and tramadol (55.75 minutes) administered separately. There was no significant difference (P&gt;0.05) in serum IL-6 before and after the administration of lidocaine, tramadol, or their combination. This study has demonstrated that the lidocaine-tramadol combination at respective doses of 3.5 and 1.5 mgkg-1 has a quicker onset and longer duration of activity when subcutaneously administered at the surgical site, in comparison with lidocaine alone and tramadol alone at respective doses of 7 and 3 mgkg-1. However, there was no remarkable difference in the serum pain biomarker (IL-6) among the three different treatments. Subcutaneous infiltration of the combination of lidocaine at 3.5 mgkg-1 with tramadol at 1.5 mgkg-1 via the inverted L block technique can be employed as an alternative to conventional lidocaine alone to achieve loco-regional analgesia for a more prolonged duration in goats to conduct laparotomy. Clinically, this drug combination could be useful in surgeries requiring extended regional anaesthesia, reducing the need for repeated dosing, hence improving animal welfare.