Specific Time Points Research Articles

External validation of the modified Marsh and Schnider models for medium-chain triglyceride propofol in target-controlled infusion anesthesia

BackgroundPropofol formulated with medium- and long-chain triglycerides (MCT/LCT propofol) has rapidly replaced propofol formulated with long-chain triglycerides (LCT propofol). Despite this shift, the modified Marsh and Schnider pharmacokinetic models developed using LCT propofol are still widely used for target-controlled infusion (TCI) of propofol. This study aimed to validate the external applicability of these models by evaluating their predictive performance during TCI of MCT/LCT propofol in general anesthesia.MethodsAdult patients (n = 48) undergoing elective surgery received MCT/LCT propofol via a TCI system using either the modified Marsh or Schnider models. Blood samples were collected at various target propofol concentrations and at specific time points, including the loss of consciousness and the recovery of consciousness (13 samples per patient). The actual plasma concentration of propofol was determined using high-performance liquid chromatography. The predictive performance of each pharmacokinetic model was assessed by calculating four parameters: inaccuracy, bias, divergence, and wobble.ResultsBoth the modified Marsh and Schnider models demonstrated predictive performances within clinically acceptable ranges for MCT/LCT propofol. The inaccuracy values were 24.4% for the modified Marsh model and 26.9% for the Schnider model. Both models showed an overall positive bias, 16.4% for the modified Marsh model and 16.6% for the Schnider model. The predictive performance of MCT/LCT propofol was comparable to that of LCT propofol, suggesting formulation changes might exert only a minor impact on the reliability of the TCI system during general anesthesia. Additionally, both models exhibited higher bias and inaccuracy at target concentrations ranging from 3.5 ~ 5 ug/ml than at concentrations between 2 ~ 3 ug/ml.ConclusionsThe modified Marsh and Schnider models, initially developed for LCT propofol, remain clinically acceptable for TCI with MCT/LCT propofol.Trial registrationThis study was registered at the Clinical Research Information Service of the Korean National Institute of Health (https://cris.nih.go.kr; registration number: KCT0002191; 06/01/2017).

Social and Environmental Factors Influencing COVID-19 Transmission and Mortalities in Developing and Developed Nations

Background: The study sought to establish environmental and social factors that influenced the transmission and mortalities of COVID-19 in developing and developed nations. The factors that were assessed included temperature, average age of the population, urbanization, population density, and percentage of old-aged people in the population. The dependent variables were COVID-19 transmission and COVID-19-related deaths. Methods: The study employed a pragmatism research philosophy. It also relied on a deductive research approach and a descriptive research design. It adopted a mixed-method approach as it used both qualitative and quantitative data. It was a cross-sectional study, given its data measurement at a particular point in time. Data was analyzed and presented using descriptive techniques. Results: Statistical analyses were conducted to quantify the relationships between various factors and COVID-19 outcomes. A Kendall’s Tau test revealed a robust negative correlation between COVID-19 cases and temperature (Tb = -0.560, p<0.005). This result was further confirmed by Spearman’s rank correlation, showing a strong negative correlation with r(13) = -0.684, p<0.007. Similarly, a strong negative correlation was observed between COVID-19 deaths and average annual temperature using both Kendall’s Tau (Tb = -0.495, p<0.014) and Spearman’s rank correlation (r(13) = -0.648, p<0.012). Age emerged as a significant factor, with a strong positive correlation found between age and both COVID-19 infections (Tb = 0.516, p<0.010; r(13) = 0.670, p<0.009) and COVID-19-related mortalities (r(13) = 0.516, p<0.029). Urbanization was also positively correlated with COVID-19 infections (Tb = 0.530, p<0.008; r(13) = 0.640, p<0.014) and COVID-19 deaths (Tb = 0.398, p<0.048; r(13) = 0.561, p<0.037). Interestingly, no significant correlation was found between population density and COVID-19 infections or deaths in both developed and developing countries, as evidenced by Kendall’s Tau (TB = 0.331, p<0.1; Tb = 0.133, p<0.511) and Spearman’s rank correlation (r(13) = 0.425, p<0.130; r(13) = 0.161, p<0.583), respectively. Moreover, the percentage of elderly individuals in a country exhibited a strong positive correlation with both COVID-19 infections (Tb = 0.464, p<0.021; r(13) = 0.642, p<0.013) and COVID-19-related deaths (r(13) = 0.541, p<0.046).Conclusion: The study focused on social, demographic, and environmental factors influencing COVID-19 incidence and mortality in developing and developed nations. The study highlights significant COVID-19 transmission and mortality disparities between developed and developing countries. Developed countries exhibited higher infection and mortality rates, coupled with elevated death rates per million and infection rates per million, as compared to their developing counterparts. The research identified a correlation between lower average annual temperatures and increased mortality in developed countries. Contrary to this, high average annual temperatures were associated with a decline in COVID-19 infections.Moreover, developed countries, characterized by higher urbanization levels, population densities, and percentages of aged individuals, experienced elevated COVID-19 infection rates. The study also unveiled a positive correlation between age and COVID-19 infections, with developed countries hosting significantly older populations than their developing counterparts. However, population density did not clearly correlate with COVID-19 infections or deaths.

Reference limits for osteocalcin in infancy and early childhood: A longitudinal birth cohort study.

The longitudinal variations in serum levels of the hormone osteocalcin is largely unknown during infancy and early childhood. Our aim was to establish reference limits for total serum osteocalcin during specific time points from birth until 5 years of age and present those in the context of sex, breastfeeding practices and gestational age (GA). Blood samples from 551 Swedish children were analysed at birth, 4, 12, 36and 60 months of age. Total serum osteocalcin was measured using the IDS-iSYS N-MID Osteocalcin assay technique. Information about the mother, birth, anthropometrics and a food diary were collected. Sex-specific and age-specific reference limits were established for the five time points. The median osteocalcin levels over time were 40.8, 90.0, 67.8, 62.2and 80.9 μg/L for boys and 38.1, 95.5, 78.3, 73.9and 92.6 μg/L for girls. Lower GA was associated to higher osteocalcin at birth, and ongoing breastfeeding was associated to higher osteocalcin levels. Osteocalcin followed a wavelike pattern with low levels in the umbilical cord and a postnatal peak during the first year which then declined and rose again by the age of five. Knowledge of this wavelike pattern and association to factors as sex, breastfeeding and GA may help clinicians to interpret individual osteocalcin levels and guide in future research.

Detecting Psychological Interventions Using Bilateral Electromyographic Wearable Sensors.

This study investigated the impact of auditory stimuli on muscular activation patterns using wearable surface electromyography (EMG) sensors. Employing four key muscles (Sternocleidomastoid Muscle (SCM), Cervical Erector Muscle (CEM), Quadricep Muscles (QMs), and Tibialis Muscle (TM)) and time domain features, we differentiated the effects of four interventions: silence, music, positive reinforcement, and negative reinforcement. The results demonstrated distinct muscle responses to the interventions, with the SCM and CEM being the most sensitive to changes and the TM being the most active and stimulus dependent. Post hoc analyses revealed significant intervention-specific activations in the CEM and TM for specific time points and intervention pairs, suggesting dynamic modulation and time-dependent integration. Multi-feature analysis identified both statistical and Hjorth features as potent discriminators, reflecting diverse adaptations in muscle recruitment, activation intensity, control, and signal dynamics. These features hold promise as potential biomarkers for monitoring muscle function in various clinical and research applications. Finally, muscle-specific Random Forest classification achieved the highest accuracy and Area Under the ROC Curve for the TM, indicating its potential for differentiating interventions with high precision. This study paves the way for personalized neuroadaptive interventions in rehabilitation, sports science, ergonomics, and healthcare by exploiting the diverse and dynamic landscape of muscle responses to auditory stimuli.

A single-institutional experience with 36 children less than 5 kilograms supported with the Berlin Heart: Comparison of congenital versus acquired heart disease.

We reviewed outcomes in all 36 consecutive children <5 kg supported with the Berlin Heart pulsatile ventricular assist device at the University of Florida, comparing those with acquired heart disease (n = 8) to those with congenital heart disease (CHD) (n = 28). The primary outcome was mortality. The Kaplan-Meier method and log-rank tests were used to assess group differences in long-term survival after ventricular assist device insertion. T-tests using estimated survival proportions were used to compare groups at specific time points. Of 82 patients supported with the Berlin Heart at our institution, 49 (49/82 = 59.76%) weighed <10 kg and 36 (36/82 = 43.90%) weighed <5 kg. Of 36 patients <5 kg, 26 (26/36 = 72.22%) were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 36 patients <5 kg was [days]: median = 109, range = 4-305.) Eight out of 36 patients <5 kg had acquired heart disease, and all eight [8/8 = 100%] were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 8 patients <5 kg with acquired heart disease was [days]: median = 50, range = 9-130.) Twenty-eight of 36 patients <5 kg had congenital heart disease. Eighteen of these 28 [64.3%] were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 28 patients <5 kg with congenital heart disease was [days]: median = 136, range = 4-305.) For all 36 patients who weighed <5 kg: 1-year survival estimate after ventricular assist device insertion = 62.7% (95% confidence interval = 48.5-81.2%) and 5-year survival estimate after ventricular assist device insertion = 58.5% (95% confidence interval = 43.8-78.3%). One-year survival after ventricular assist device insertion = 87.5% (95% confidence interval = 67.3-99.9%) in acquired heart disease and 55.6% (95% confidence interval = 39.5-78.2%) in CHD, P = 0.036. Five-year survival after ventricular assist device insertion = 87.5% (95% confidence interval = 67.3-99.9%) in acquired heart disease and 48.6% (95% confidence interval = 31.6-74.8%) in CHD, P = 0.014. Pulsatile ventricular assist device facilitates bridge to transplantation in neonates and infants weighing <5 kg; however, survival after ventricular assist device insertion in these small patients is less in those with CHD in comparison to those with acquired heart disease.

Development and internal validation of machine learning models for personalized survival predictions in spinal cord glioma patients

BACKGROUND CONTEXTNumerous factors have been associated with the survival outcomes in patients with spinal cord gliomas (SCG). Recognizing these specific determinants is crucial, yet it is also vital to establish a reliable and precise prognostic model for estimating individual survival outcomes. OBJECTIVEThe objectives of this study are twofold: first, to create an array of interpretable machine learning (ML) models developed for predicting survival outcomes among SCG patients; and second, to integrate these models into an easily navigable online calculator to showcase their prospective clinical applicability. STUDY DESIGNThis was a retrospective, population-based cohort study aiming to predict the outcomes of interest, which were binary categorical variables, in SCG patients with ML models. PATIENT SAMPLEThe National Cancer Database (NCDB) was utilized to identify adults aged 18 years or older who were diagnosed with histologically confirmed SCGs between 2010 and 2019. OUTCOME MEASURESThe outcomes of interest were survival outcomes at three specific time points postdiagnosis: 1, 3, and 5 years. These outcomes were formed by combining the “Vital Status” and “Last Contact or Death (Months from Diagnosis)” variables. Model performance was evaluated visually and numerically. The visual evaluation utilized receiver operating characteristic (ROC) curves, precision-recall curves (PRCs), and calibration curves. The numerical evaluation involved metrics such as sensitivity, specificity, accuracy, area under the PRC (AUPRC), area under the ROC curve (AUROC), and Brier Score. METHODSWe employed five ML algorithms—TabPFN, CatBoost, XGBoost, LightGBM, and Random Forest—along with the Optuna library for hyperparameter optimization. The models that yielded the highest AUROC values were chosen for integration into the online calculator. To enhance the explicability of our models, we utilized SHapley Additive exPlanations (SHAP) for assessing the relative significance of predictor variables and incorporated partial dependence plots (PDPs) to delineate the influence of singular variables on the predictions made by the top performing models. RESULTSFor the 1-year survival analysis, 4,913 patients [5.6% with 1-year mortality]; for the 3-year survival analysis, 4,027 patients (11.5% with 3-year mortality]; and for the 5-year survival analysis, 2,854 patients (20.4% with 5-year mortality) were included. The top models achieved AUROCs of 0.938 for 1-year mortality (TabPFN), 0.907 for 3-year mortality (LightGBM), and 0.902 for 5-year mortality (Random Forest). Global SHAP analyses across survival outcomes at different time points identified histology, tumor grade, age, surgery, radiotherapy, and tumor size as the most significant predictor variables for the top-performing models. CONCLUSIONSThis study demonstrates ML techniques can develop highly accurate prognostic models for SCG patients with excellent discriminatory ability. The interactive online calculator provides a tool for assessment by physicians (https://huggingface.co/spaces/MSHS-Neurosurgery-Research/NCDB-SCG). Local interpretability informs prediction influences for a given individual. External validation across diverse datasets could further substantiate potential utility and generalizability. This robust, interpretable methodology aligns with the goals of precision medicine, establishing a foundation for continued research leveraging ML's predictive power to enhance patient counseling.

Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model.

Angiotensin receptor-neprilysin inhibitor (ARNi), comprised of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has established itself as a safe and effective intervention for hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension. Dahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were employed in this study to investigate the anti-hypertensive efficacy of S086 and compare it with the first ARNi-LCZ696. The study showed that oral administration of S086 dose-dependently lowered blood pressure (P < 0.001). The middle dosage of S086 (23 mg/kg) exhibited efficacy comparable to LCZ696 (68 mg/kg), while also demonstrating superiority at specific time points (P < 0.05). Notably, water consumption slightly decreased post-treatment compared to the vehicle group. Furthermore, there were significant increases in natriuresis and diuresis observed on the first day of treatment with 23 mg/kg and 68 mg/kg S086 (P < 0.001). However, over the course of treatment, the effects in all treatment groups gradually diminished. This study demonstrates the anti-hypertensive efficacy of S086 in DSS hypertensive rat model, offering promising avenues for the clinical development of S086 as a hypertension treatment.

Physiological cell bioprinting density in human bone-derived cell-laden scaffolds enhances matrix mineralization rate and stiffness under dynamic loading.

Human organotypic bone models are an emerging technology that replicate bone physiology and mechanobiology for comprehensive in vitro experimentation over prolonged periods of time. Recently, we introduced a mineralized bone model based on 3D bioprinted cell-laden alginate-gelatin-graphene oxide hydrogels cultured under dynamic loading using commercially available human mesenchymal stem cells. In the present study, we created cell-laden scaffolds from primary human osteoblasts isolated from surgical waste material and investigated the effects of a previously reported optimal cell printing density (5 × 106 cells/mL bioink) vs. a higher physiological cell density (10 × 106 cells/mL bioink). We studied mineral formation, scaffold stiffness, and cell morphology over a 10-week period to determine culture conditions for primary human bone cells in this microenvironment. For analysis, the human bone-derived cell-laden scaffolds underwent multiscale assessment at specific timepoints. High cell viability was observed in both groups after bioprinting (>90%) and after 2 weeks of daily mechanical loading (>85%). Bioprinting at a higher cell density resulted in faster mineral formation rates, higher mineral densities and remarkably a 10-fold increase in stiffness compared to a modest 2-fold increase in the lower printing density group. In addition, physiological cell bioprinting densities positively impacted cell spreading and formation of dendritic interconnections. We conclude that our methodology of processing patient-specific human bone cells, subsequent biofabrication and dynamic culturing reliably affords mineralized cell-laden scaffolds. In the future, in vitro systems based on patient-derived cells could be applied to study the individual phenotype of bone disorders such as osteogenesis imperfecta and aid clinical decision making.

Endosperm cell death: roles and regulation in angiosperms.

Double fertilization in angiosperms results in the formation of a second zygote, the fertilized endosperm. Unlike its embryo sibling, the endosperm is a transient structure that eventually undergoes developmentally controlled programmed cell death (PCD) at specific time points of seed development or germination. The nature of endosperm PCD exhibits a considerable diversity, both across different angiosperm taxa and within distinct endosperm tissues. In endosperm-less species, PCD might cause central cell degeneration as a mechanism preventing the formation of a fertilized endosperm. In most other angiosperms, embryo growth necessitates the elimination of surrounding endosperm cells. Nevertheless, complete elimination of the endosperm is rare and, in most cases, specific endosperm tissues persist. In mature seeds, these persisting cells may be dead, such as the starchy endosperm in cereals, or remain alive to die only during germination, like the cereal aleurone or the endosperm of castor beans. In this review, we explore current knowledge surrounding the cellular, molecular, and genetic aspects of endosperm PCD, and the influence environmental stresses have on PCD processes. Overall, this review provides an exhaustive overview of endosperm PCD processes in angiosperms, shedding light on its diverse mechanisms and its significance in seed development and seedling establishment.

Collaborative Development of a Farm Systems Learning Platform “4D Virtual Farm”

Over the past 20 years, a lower percentage of veterinary and animal science students entering Australian and New Zealand schools have a background or ongoing contact with livestock production systems. The increasing use of digital technologies over the same time provides a practical option to introduce students to the seasonal operations on livestock farms. This article describes the development of the 4D Virtual Farm, established to showcase 11 representative livestock farms across Australasia allowing students to virtually travel through seasons and place over each farming enterprise. Students can virtually visit different beef cattle, prime lamb, wool-sheep and dairy cattle farms, and a piggery. Any electronic device connected to the web including mobile phones, tablets, computers, and virtual reality headsets can be used to view the enterprises. For educators, the virtual farm can be used for a range of teaching and learning scenarios, such as demonstration of a particular production system via weblink for lectures or embedding within learning management systems. It also allows students to start at a particular point in time and space and guide themselves to other areas for self-learning or for a range of assessment tasks. This site provides an example that could be used in other teaching areas including abattoirs, exotic diseases, surgery, communication, and many other veterinary examples.

Effect of tempo on the age-related changes in temporal expectation driven by rhythms.

Temporal expectation refers to the capacity to allocate resources at a particular point in time, enabling us to enhance our behavior performance. Empirical evidence indicates that, among younger adults, temporal expectation can be driven by rhythm (i.e., regular sequences of stimuli). However, whether there are age-related changes in rhythm-based temporal expectation has not been clearly established. Furthermore, whether tempo can influence the relationship between rhythm-based temporal expectation and aging remains unexplored. To address these questions, both younger and older participants took part in a rhythm-based temporal expectation task, engaging three distinct tempos: 600 ms (fast), 1800 ms (moderate), or 3000 ms (slow). The results demonstrated that temporal expectation effects (i.e., participants exhibited significantly faster responses during the regular trials compared to the irregular trials) were observed in both the younger and older participants under the moderate tempo condition. However, in the fast and slow tempo conditions, the temporal expectation effects were solely observed in the younger participants. These findings revealed that rhythm-based temporal expectations can be preserved during aging but within a specific tempo range. When the tempo falls within the range of either being too fast or too slow, it can manifest age-related declines in temporal expectations driven by rhythms.

Sustained Systemic Antioxidative Effects of Intermittent Theta Burst Stimulation beyond Neurodegeneration: Implications in Therapy in 6-Hydroxydopamine Model of Parkinson's Disease.

Parkinson's disease (PD) is manifested by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and caudoputamen (Cp), leading to the development of motor and non-motor symptoms. The contribution of oxidative stress to the development and progression of PD is increasingly recognized. Experimental models show that strengthening antioxidant defenses and reducing pro-oxidant status may have beneficial effects on disease progression. In this study, the neuroprotective potential of intermittent theta burst stimulation (iTBS) is investigated in a 6-hydroxydopamine (6-OHDA)-induced PD model in rats seven days after intoxication which corresponds to the occurrence of first motor symptoms. Two-month-old male Wistar rats were unilaterally injected with 6-OHDA to mimic PD pathology and were subsequently divided into two groups to receive either iTBS or sham stimulation for 21 days. The main oxidative parameters were analyzed in the caudoputamen, substantia nigra pars compacta, and serum. iTBS treatment notably mitigated oxidative stress indicators, simultaneously increasing antioxidative parameters in the caudoputamen and substantia nigra pars compacta well after 6-OHDA-induced neurodegeneration process was over. Serum analysis confirmed the systemic effect of iTBS with a decrease in oxidative markers and an increase in antioxidants. Prolonged iTBS exerts a modulatory effect on oxidative/antioxidant parameters in the 6-OHDA-induced PD model, suggesting a potential neuroprotective benefit, even though at this specific time point 6-OHDA-induced oxidative status was unaltered. These results emphasize the need to further explore the mechanisms of iTBS and argue in favor of considering it as a therapeutic intervention in PD and related neurodegenerative diseases.

Time-Course Responses of Apple Leaf Endophytes to the Infection of Gymnosporangium yamadae.

Apple rust, caused by Gymnosporangium yamadae, poses a significant challenge to apple production. Prior studies have underscored the pivotal role played by endophytic microbial communities, intimately linked with the host, in influencing plant diseases and their pathogenic outcomes. The objective of this study is to scrutinize alternations in endophytic microbial communities within apple leaves at different stages of apple rust using high-throughput sequencing technology. The findings revealed a discernible pattern characterized by an initial increase and subsequent decrease in the alpha diversity of microbial communities in diseased leaves. A microbial co-occurrence network analysis revealed that the complexity of the bacterial community in diseased leaves diminished initially and then rebounded during the progression of the disease. Additionally, employing the PICRUSt2 platform, this study provided preliminary insights into the functions of microbial communities at specific disease timepoints. During the spermogonial stage, endophytic bacteria particularly exhibited heightened activity in genetic information processing, metabolism, and environmental information processing pathways. Endophytic fungi also significantly enriched a large number of metabolic pathways during the spermogonial stage and aecial stage, exhibiting abnormally active life activities. These findings establish a foundation for comprehending the role of host endophytes in the interaction between pathogens and hosts. Furthermore, they offer valuable insights for the development and exploitation of plant endophytic resources, thereby contributing to enhanced strategies for managing apple rust.

Spatiotemporal variation of water balance components in Mashhad catchment, Iran: Investigating the impact of changes in climatic data and land use

Abstract The research aims to investigate the spatiotemporal changes of water balance components and distinguish the relative impacts of climatic data and land-use on groundwater level in northeastern Iran. This investigation employs the WetSpass-M model to estimate water balance and the Mann-Kendall test alongside Sen's slope estimator to evaluate trend. The study also assesses mean annual water balance components, considering diverse combinations of land-use and soil. The findings offer a hydrological insight, revealing that 14% of precipitation results in runoff, 29% of that recharging the aquifer; the remaining portion is lost through evapotranspiration. The trends in precipitation and simulated water components are not significant but a significant downward trend in groundwater is observed beyond a specific point in time. Based on this outcome, as well as the analysis of land-use changes, it was speculated that human activities in this fast-developing region might be implicated in the decline in groundwater levels. Analysis of water balance components in various soil and land-use combinations indicates that evapotranspiration exhibits greater variability within the land-cover class, while recharge is more influenced by soil texture. These findings enhance our understanding for identifying potential sites for artificial recharge and determining sustainable groundwater withdrawals based on spatiotemporal recharge patterns.

Short and decadal impacts of seafloor physical perturbation on the abundances of Lebensspuren ‘traces of life’ in the Peru Basin manganese nodule province

Interest in deep-sea mining for polymetallic nodules as an alternative source to onshore mines for various high-technology metals has risen in recent years, as demands and costs have increased. The need for studies to assess its short- and long-term consequences on polymetallic nodule ecosystems is therefore also increasingly prescient. Recent image-based expedition studies have described the temporal impacts on epi-/megafauna seafloor communities across these ecosystems at particular points in time. However, these studies have failed to capture information on large infauna within the sediments or give information on potential transient and temporally limited users of these areas, such as mobile surface deposit feeders or fauna responding to bloom events or food fall depositions. This study uses data from the Peru Basin polymetallic nodule province, where the seafloor was previously disturbed with a plough harrow in 1989 and with an epibenthic sled (EBS) in 2015, to simulate two contrasting possible impact forms of mining disturbance. To try and address the shortfall on information on transient epifauna and infauna use of these various disturbed and undisturbed areas of nodule-rich seafloor, images collected 6 months after the 2015 disturbance event were inspected and all Lebensspuren, ‘traces of life’, were characterized by type (epi- or infauna tracemakers, as well as forming fauna species where possible), along with whether they occurred on undisturbed seafloor or regions disturbed in 1989 or 2015. The results show that epi- and endobenthic Lebensspuren were at least 50% less abundant across both the ploughed and EBS disturbed seafloors. This indicates that even 26 years after disturbance, sediment use by fauna may remain depressed across these areas.

Computerised modified paramedian approach technique versus conventional midline approach technique of lumbar puncture: a randomised control trial protocol

IntroductionThe lumbar puncture (LP) technique is widely used for diagnostic and therapeutic purposes. In recent years, the paramedian approach technique (PAT) has gained increasing interest due to its advantages over...

Co-treatment with bone marrow-derived mesenchymal stem cells and curcumin improved angiogenesis in myocardium in a rat model of MI.

The cardioprotective properties of mesenchymal stem cells and the therapeutic potential of curcumin (CUR) have been explored. Combining these approaches may enhance stem cell effectiveness and expedite healing. This study aimed to investigate the synergistic effects of co-treating bone marrow mesenchymal stem cells (BMSCs) with curcumin on vascular endothelial growth factor (VEGF) levels, in a rat model of myocardial ischemia (MI). Sixty-five male rats were divided into four groups: G1 (healthy control), G2 (MI induced by isoproterenol hydrochloride), G3 (treated with BMSCs), and G4 (co-treated with curcumin and BMSCs). Blood and tissue samples were collected at specific time points (day 1, 7, 15 and 21) after MI induction. Serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTnI), aspartate aminotransferase (AST), CK-MB and VEGF were measured. VEGF mRNA and protein expression were evaluated using RT-qPCR and Western blot techniques. Histopathological assessments were performed using H&E staining and CD31 immunofluorescence staining. VEGF expression significantly increased on days 7 and 15 in the CUR-BMSCs group, peaking on day 7. Western blot analysis confirmed elevated VEGF protein expression on days 7 and 15 post-MI. ELISA results demonstrated increased serum VEGF levels on days 7 and 15, reaching the highest level on day 7 in CUR-BMSCs-treated animals. Treated groups showed lower levels of LDH, AST, CK, CK-MB and cTnI compared to the untreated MI group. H&E staining revealed improved myocardial structure, increased formation of new capillaries, in both treatment groups compared to the MI group. Combining curcumin with BMSCs promotes angiogenesis in the infarcted myocardium after 15days of MI induction. These findings suggest the potential of this combined therapy approach for enhancing cardiac healing and recovery.

Online Corrections to Neural Policy Guidance for Pinpoint Powered Descent

This study presents incremental correction methods for refining neural network parameters or control functions entering into a continuous-time dynamic system to achieve improved solution accuracy in satisfying the interim point constraints placed on the performance output variables. The proposed approach is to linearize the dynamics around the baseline values of its arguments and then to solve for the corrective input required to transfer the perturbed trajectory to precisely known or desired values at specific time points, in other words, the interim points. Depending on the type of decision variables to adjust, parameter correction and control function correction methods are developed. These incremental correction methods can be used as a means to compensate for the prediction errors of pretrained neural networks in real-time applications where high accuracy of the prediction of dynamical systems at prescribed time points is imperative. In this regard, the online update approach can be useful for enhancing overall targeting accuracy of finite-horizon control subject to point constraints using a neural policy. A numerical example demonstrates the effectiveness of the proposed approach in an application to a powered descent problem on Mars.

Evaluation of Teachers' Technological Pedagogical Content Knowledge (TPACK) Understanding Profile

This research aimed to assess teachers' understanding of the Technological Pedagogical Content Knowledge (TPACK) structure and investigate whether TPACK components differ based on gender characteristics. The research method used was a cross-sectional survey, a quantitative approach aimed at examining a condition at a specific point in time and exploring relationships between variables. Respondents were randomly selected from 102 teachers spread across Lombok Island, comprising 48 female teachers and 56 male teachers. The research instrument utilized a TPACK questionnaire measuring CK, PK, TK, TPTCK, and TPCK, adapted from Liang et al., 2013. The analysis results indicated that teachers demonstrated a solid understanding of Content Knowledge (CK) and Pedagogical Knowledge (PK), signifying a strong grasp of the taught material and effective teaching techniques. However, concerning Pedagogical Content Knowledge (PCK), their understanding of how to teach specific content required further attention. Nevertheless, they exhibited a robust understanding of Technological Knowledge (TK), Technological Pedagogical Content Knowledge (TPTCK), and Pedagogical Content Knowledge (TPCK), although the level of understanding in TPCK was slightly higher than TPTCK. Meanwhile, the gender-based analysis showed significant differences in TPACK understanding between the genders in the TK, TPTCK, and TPCK components, but no significant differences were observed in the PK, CK, and PCK components. This highlights the importance of understanding gender differences related to specific aspects of technology, education, and content knowledge. Further research or in-depth analysis is needed to comprehend the underlying factors causing these differences and their implications within the educational context and curriculum development.

It was a Different Time: Judging Historical Figures by Today's Moral Standards

ABSTRACTHow should we respond to historical figures who played an important role in their country's history but have also perpetrated acts of great evil? Much of the existing philosophical literature on this topic has focused on explaining why it may be wrong to celebrate such figures. However, a common response that is made in popular discussions around these issues is that we should not judge historical figures by today's standards. Our goal in this article is to examine the most plausible way to understand this objection. We will examine three different interpretations of this argument. First, we will examine a view we call Temporal Moral Relativism, according to which moral standards are relative to particular points in time. Next, we outline Blame Relativism, the view that people from the past may be excused from blame for acts of conventionalised wrongdoing. Finally, we outline Ideals Relativism, according to which our moral ideals are partially relative to the time in which we live. We argue that Ideals Relativism provides the most plausible interpretation of this argument.