Search Results (241)

The integration of low Earth orbit (LEO) satellite constellations into the Global Navigation Satellite System (GNSS) has emerged as a prominent research focus, as LEO satellites can significantly enhance the precision of GNSS positioning, navigation, and timing (PNT) services. In the design of LEO navigation constellations, the development of an efficient broadcast ephemeris model is critical for delivering high-accuracy navigation solutions. This study extends the conventional 16-parameter Keplerian broadcast ephemeris model by proposing enhanced 18-, 20-, 22-, and 24-parameter models, ensuring compatibility with existing GNSS ephemeris standards. The performance of these models was evaluated using precise science orbit from five satellites at varying altitudes, ranging from 320 km to 1336 km. By analyzing fitting errors, Signal-in-Space Range Error (SISRE), and Message Size Bits (MSB) across different fitting arc durations and parameter counts, the optimal model configuration was identified. The results demonstrate that the 22-parameter model, which was constructed by augmenting the standard 16-parameter ephemeris with $(\dot{a}$, $\dot{n}$, $Crs3$, $Crc3$, $Crs1$, $Crc1$) delivers the best balance of accuracy and efficiency. With a fitting arc length of 20 min, the SISRE for the GRACE-A (320 km), GRACE-C (475 km), Sentinel-2A (786 km), HY-2A (966 km), and Sentinel-6A (1336 km) satellites were measured at 8.88 cm, 6.21 cm, 2.87 cm, 2.11 cm, and 0.75 cm, respectively. Meanwhile, the corresponding MSB remained compact at 501, 490, 491, 487, and 476 bits. These findings confirm that the proposed 22-parameter broadcast ephemeris model meets the stringent accuracy requirements for next-generation LEO-augmented GNSSs, paving the way for enhanced global navigation services. Full article

In general, the justification for the divine punishment in the Christian cosmos hinges on the notion of free will. Despite doctrinal complexities involving sin, grace, and divine sovereignty, individuals are held morally responsible for choosing evil over good. According to an ancient Chinese legend, however, the tyrant King Zhou (11th C. BCE) who lost his throne due to a changed mandate from Heaven was born with extreme evil tendencies. But if his evilness was determined before his birth and all his evil deeds are consequences of his natural tendencies, what might justify his punishment? Through an examination of Confucian responses to this question, this essay argues that Confucians did not ground moral responsibility in volitional freedom but rather in the extremity of one’s moral conduct. Their framework reveals a distinctive form of compatibilism—one in which blame is assigned not on the basis of freedom to choose otherwise but on how radically one’s actions deviate from shared ethical expectations. This suggests that the assumption of free will as a necessary condition for moral responsibility may reflect culturally specific intuitions, rather than a universal moral standard. Full article

Background/Objectives: Inflammation plays a key role in acute coronary syndromes (ACS). The systemic immune-inflammation index (SII), which integrates immune and inflammatory markers, may serve as a valuable prognostic tool. This study aimed to evaluate the utility of SII as a short-term predictor of mortality and major adverse cardiovascular and cerebral events (MACCE) in ACS patients. Methods: A retrospective analysis was conducted on 964 ACS patients admitted in 2023. SII was calculated from admission hematological parameters. Primary and secondary outcomes were 30-day mortality and MACCE, respectively. Results: SII levels differed significantly across ACS subtypes (p < 0.001), highest in ST-segment elevation myocardial infarction (STEMI) and lowest in unstable angina. SII was markedly higher in deceased patients (2003.79 ± 1601.17) vs. survivors (722.04 ± 837.25; p < 0.001) and remained an independent predictor of mortality (OR = 1.038, p < 0.001). Similarly, SII was elevated in MACCE cases (1717 ± 1611.32) vs. non-MACCE (664.68 ± 713.11; p < 0.001) and remained predictive in multivariate analysis (OR = 1.080, p < 0.001). Predictive accuracy for MACCE was moderate (AUC = 0.762), improved when combined with GRACE 2, especially in specificity (p = 0.07). In STEMI, SII had excellent accuracy (AUC = 0.874), outperforming neutrophil–lymphocyte ratio and C-reactive protein. SII rose at 24 h and declined at 48 h in STEMI, with a slower decline in MACCE patients. Conclusions: SII proved to be a cost-effective biomarker reflecting inflammation, immunity, and thrombosis. Elevated SII predicted short-term MACCE and mortality in ACS, with improved prognostic power when combined with GRACE 2. Persistent elevation may signal ongoing inflammation and increased MACCE risk. Full article

Clozapine, a second-generation antipsychotic known for its effectiveness in treating resistant schizophrenia, is often linked with serious hematological side effects, particularly neutropenia and agranulocytosis. This review investigates the underlying pathophysiological mechanisms of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA), outlines associated risk factors, and evaluates current clinical management strategies. Clozapine’s pharmacological profile, marked by its antagonism of dopamine D4 and serotonin receptors, contributes to both its therapeutic advantages and hematological toxicity. Epidemiological data show a prevalence of CIN and CIA at approximately 3.8% and 0.9%, respectively, with onset typically occurring within the first six months of treatment. Key risk factors include older age, Asian and African American ethnicity, female sex, and certain genetic predispositions. The development of CIN and CIA may involve bone marrow suppression and autoimmune mechanisms, although the exact processes remain partially understood. Clinical presentation often includes nonspecific symptoms such as fever and signs of infection, necessitating regular hematological monitoring in accordance with established guidelines. Management strategies include dosage adjustments, cessation of clozapine, and the administration of granulocyte colony-stimulating factors (G-CSF). Advances in pharmacogenomics show promise for predicting susceptibility to CIN and CIA, potentially improving patient safety. This review emphasizes the importance of vigilant monitoring and personalized treatment approaches to reduce the risks associated with clozapine therapy. Full article

Background: Hypotension following epidural labor analgesia (ELA) is its most common complication, affecting approximately 20% of patients and posing risks to both maternal and fetal health. As digital tools and predictive analytics increasingly shape perioperative and obstetric anesthesia practices, real-world implementation data are needed to guide their integration into clinical care. Current monitoring practices rely on intermittent non-invasive blood pressure (NIBP) measurements, which may delay recognition and treatment of hypotension. The Hypotension Prediction Index (HPI) algorithm uses continuous arterial waveform monitoring to predict hypotension for potentially earlier intervention. This clinical trial evaluated the feasibility, acceptability, and efficacy of continuous HPI-guided treatment in reducing time-to-treatment for ELA-associated hypotension and improving maternal hemodynamics. Methods: This was a prospective randomized controlled trial design involving healthy pregnant individuals receiving ELA. Participants were randomized into two groups: Group CM (conventional monitoring with NIBP) and Group HPI (continuous noninvasive blood pressure monitoring). In Group HPI, hypotension treatment was guided by HPI output; in Group CM, treatment was based on NIBP readings. Feasibility, appropriateness, and acceptability outcomes were assessed among subjects and their bedside nurse using the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM) instruments. The primary efficacy outcome was time-to-treatment of hypotension, defined as the duration between onset of hypotension and administration of a vasopressor or fluid therapy. This outcome was chosen to evaluate the clinical responsiveness enabled by HPI monitoring. Hypotension is defined as a mean arterial pressure (MAP) < 65 mmHg for more than 1 min in Group CM and an HPI threshold < 75 for more than 1 min in Group HPI. Secondary outcomes included total time in hypotension, vasopressor doses, and hemodynamic parameters. Results: There were 30 patients (Group HPI, n = 16; Group CM, n = 14) included in the final analysis. Subjects and clinicians alike rated the acceptability, appropriateness, and feasibility of the continuous monitoring device highly, with median scores ≥ 4 across all domains, indicating favorable perceptions of the intervention. The cumulative probability of time-to-treatment of hypotension was lower by 75 min after ELA initiation in Group HPI (65%) than Group CM (71%), although this difference was not statistically significant (log-rank p = 0.66). Mixed models indicated trends that Group HPI had higher cardiac output (β = 0.58, 95% confidence interval −0.18 to 1.34, p = 0.13) and lower systemic vascular resistance (β = −97.22, 95% confidence interval −200.84 to 6.40, p = 0.07) throughout the monitoring period. No differences were found in total vasopressor use or intravenous fluid administration. Conclusions: Continuous monitoring and precision hypotension treatment is feasible, appropriate, and acceptable to both patients and clinicians in a labor and delivery setting. These hypothesis-generating results support that HPI-guided treatment may be associated with hemodynamic trends that warrant further investigation to determine definitive efficacy in labor analgesia contexts. Full article

Background: Pneumococcal vaccination rates in the United States (US) remain suboptimal, especially for adults aged 19 to 64 with high-risk medical conditions. Community-pharmacy-based immunization services increase vaccine access, particularly in rural areas. This study describes the provision of pneumococcal immunization services, assesses the processes used to identify and confirm patient eligibility, and determines barriers to immunization services in rural community pharmacies. Methods: A cross-sectional survey was emailed to members of the Rural Research Alliance of Community Pharmacies, located in the southeastern US. The survey assessed which pneumococcal vaccines were offered, age groups, prescription requirements, and how patient eligibility was determined. In addition, participants were asked to rate a series of patient-related and organizational barriers to pneumococcal vaccination. Results: Ninety-four pharmacies completed the survey, with most (96.8%) offering pneumococcal vaccines, most commonly PCV20 (95.6%). Most pharmacies vaccinated patients upon request (98.9%) or when patients presented with a prescription (82.4%), but few proactively contacted patients to schedule the vaccination (17.6%). Pharmacists most often administered pneumococcal vaccines to patients aged 65 and older and used patient age and immunization information systems to identify eligible patients. The most common patient-related barrier was the patient’s belief that they do not need the vaccine. The most common organizational barriers were inadequate reimbursements for vaccine administration and vaccine products. Conclusions: Pneumococcal vaccinations are commonly offered in rural community pharmacies, which play an important role in immunization access. With recent guideline changes to the age-based recommendation, there is an opportunity to optimize strategies to increase vaccine uptake. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the most abundant ω-3 fatty acids in the membrane phospholipids of the mammalian brain, and dietary DHA plays an important role in brain development and maintenance of brain structure. In this study, we investigated whether peri-natal supplementation of DHA can alleviate autistic-like behaviors in a genetic risk/stress mouse model and how it alters lipid peroxidation activity and GABAergic system gene expression in the forebrain. Pregnant heterozygous serotonin transporter knockout (SERT-KO) and wild-type (WT) dams were placed in either non-stressed control conditions or chronic variable stress (CVS) conditions and fed either a control diet or a DHA-rich (1% by weight) diet. Offspring of each group were assessed for anxiety and autism-associated behavior at post-natal day 60 using an open field test, elevated plus maze test, repetitive behavior, and the 3-chamber social approach test. A liquid chromatography-mass spectrometry (LC-MS)-based method was used to follow changes in levels of lipid peroxidation products in the cerebral cortex. Male offspring of prenatally stressed SERT-het KO dams exhibited decreased social preference behaviors and increased repetitive grooming behaviors compared to WT control offspring. Moreover, DHA supplementation in male SERT-het mice decreased frequency of grooming behaviors albeit showing no associated effects on social behaviors. Regardless of stress conditions, supplementation of DHA to the WT mice did not result in alterations in grooming nor social interaction in the offspring. Furthermore, no apparent changes were observed in the lipid peroxidation products comparing the stressed and non-stressed brains. Gad2 was downregulated in the cortex of female offspring of prenatally stressed SERT-KO dams, and this change appeared to be rescued by DHA supplementation in offspring. Gad2 was upregulated in the striatum of male offspring of prenatally stressed SERT-KO dams, but DHA did not significantly alter the expression compared to the control diet condition. Full article

HIV-1 proviral landscapes were investigated using near-full-length HIV single-genome sequencing on blood samples from five children with vertically acquired infection and on ART for ~7–9 years. Proviral structures were compared to published datasets in children prior to ART, children on short-term ART, and adults on ART. We found a strong selection for large internal proviral deletions in children, especially deletions of the env gene. Only 2.5% of the proviruses were sequence-intact, lower than in the comparative datasets from adults. Of the proviruses that retained the env gene, >80% contained two or more defects, most commonly stop codons and/or gag start mutations. Significantly fewer defects in the major splice donor site (MSD) and packaging signal were found in the children on short or long-term ART compared to the adults, and tat was more frequently defective in children. These results suggest that different selection pressures may shape the proviral landscape in children compared to adults and reveal potentially different genetic regions to target for measuring the intact HIV reservoir and for achieving HIV remission in children. Full article

Anurans, commonly known as frogs and toads, comprise a diverse group of amphibians distributed across all continents except Antarctica. This manuscript provides a detailed overview of the global anuran fauna, emphasizing their biology, remarkable adaptations, and ecological importance. A particular focus is placed on their specialized cutaneous glands, which are crucial for defense, communication, and survival. These glands secrete a diverse array of bioactive compounds, including peptides, alkaloids, and other secondary metabolites, shaped by evolutionary pressures. Among these compounds, toxins with potent antimicrobial properties stand out due to their ability to combat a broad spectrum of microbial pathogens. We explore the chemical diversity of these secretions, analyzing their modes of action and their potential applications in combating antibiotic-resistant bacteria and other pathogens. By integrating knowledge, this study underscores the importance of anurans as both ecological keystones and a valuable resource for biotechnological innovations. Furthermore, it highlights the urgent need to conserve anuran biodiversity for harnessing their potential in the development of novel antimicrobial agents to address global health challenges. Full article

PFASs are widely present and persistent in the environment, and exposure can occur via multiple pathways. Human and animal PFAS exposures have been associated with alterations in thyroid hormones, hepatotoxicity, and other adverse effects. This study evaluated the subchronic toxicities of four specific PFASs in 90-day oral rat studies. Studies were conducted in male and female Sprague–Dawley rats exposed to PFASs in corn oil via oral gavage. The PFASs studied were 1H,1H,9H-perfluorononyl acrylate (PFNAC), 1H,1H,2H,2H-perfluorohexyl iodide (PFHI), methyl heptafluoropropyl ketone (MHFPK), and 2-chloro-2,3,3,3-tetrafluoropropanoic acid (CTFPA). High doses were 10 mg/kg-day (male) and 30 mg/kg-day (female) for PFNAC, 200 mg/kg-day for PFHI, 300 mg/kg-day for MHFPK, and 30 (male) and 100 mg/kg-day (female) for CTFPA. The four lower doses for each PFAS were spaced at two- or threefold dose increments. The most consistent effect was dose-dependent increases in the relative and absolute liver weights for PFNAC, PFHI, and CTFPA but not for MHFPK. Increased liver weights were correlated with findings of hepatocellular hypertrophy. Increased kidney weights for PFNAC and PFHI were correlated with increased incidence of minimal tubule epithelial hypertrophy (PFNAC) or increased incidence and severity of chronic progressive nephropathy and hyaline droplet accumulation (PFHI). There were no compound-related effects on morbidity and mortality or overt signs of toxicity. Full article

Some PFASs are immunotoxic in rodent models and associated with diminished vaccine response in exposed humans. This study assessed the immunotoxicity of four PFASs via the T cell-dependent IgM antibody response (TDAR) to sheep red blood cells (SRBCs) in adult male rats following 28-day oral repeat dosing. The PFASs included 1H,1H,9H-perfluorononyl acrylate (PFNAC), 1H,1H,2H,2H-perfluorohexyl iodide (PFHI), 2-chlorotetrafluoropropionic acid (CTFPA), and 3,3,4,4,5,5,5-heptafluoropentan-2-one (MHFPK), administered in corn oil. The positive control was cyclophosphamide (CPS). Rats were dosed with vehicle or PFAS from Days 0 to 27. On Day 22, an immunogenic dose of SRBCs was administered intravenously. Positive control animals were administered CPS by intraperitoneal injection from Days 22–27. On Day 28, the animals were euthanized; blood, thymus, and spleen samples were collected and weighed. Serum IgM was quantified by enzyme-linked immunosorbent assay. Body weights were unaffected in PFAS-treated rats, except for 3 and 10 mg/kg/day PFNAC-treated rats on Days 24, 27, and 28. Relative spleen and thymus weights and serum IgM levels were not affected by the PFASs at the doses tested, whereas CPS-treated animals had significant decreases in these parameters. The rat TDAR, as assessed by the anti-SRBC IgM response, was not affected by these four PFAS test agents following a 28-day oral exposure. Full article

The tomato leaf miner Phthorimaea (syn. Tuta) absoluta (Lepidoptera: Gelechiidae) is invasive in many agricultural regions. Its larvae feed inside leaf mines and tomato fruits, causing yield losses. Repeated sprays of insecticides disrupt agri-ecosystems. Conducting three open-field tomato experiments, we assessed whether formulations of entomopathogenic nematodes could improve the efficacy of these promising biocontrol agents or whether other nature-based agents such as pyrethrin or spinosad would be the better option(s), as compared to a standard insecticide. Steinernema carpocapsae formulated in an alkyl polyglycoside polymeric surfactant, in canola oil, or mixed in both reduced 37 to 68% of pest larvae within two weeks post-treatment, followed by the botanical pyrethrin (48%). Neither spinosad nor lambda cyhalothrin achieved sufficient control. Increasing the frequency of treatments to every two weeks moderately increased efficacy. Positively, the nematodes can, if properly formulated and applied, still be recovered alive from leaf surfaces up to two hours after spraying, indicating that they have time to enter the leaf mines. A small proportion can even be still extracted alive from the leaf mines one week later. Despite these promising results, further research is needed to improve the efficacy of nature-based management options for use against this pest, with the aim of ultimately reducing reliance on chemical insecticides and minimizing the impact on agri-ecosystems. Full article

Background/Objectives: Polycystic liver disease (PLD) is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). PLD is more prevalent in women, and women have larger liver cysts, possibly due to estrogen-related mechanisms. Maternal estrogen levels normally increase during pregnancy. Thus, we investigated the pregnancy-associated increase in liver volume, liver cyst volume, total kidney volume (TKV), and kidney cyst growth rates in ADPKD patients. Methods: Kidney, liver, and cyst volumes were measured in 16 ADPKD patients by magnetic resonance imaging (MRI) at multiple timepoints before and after pregnancy. The log-transformed TKV, liver volume, and cyst volume growth rates during a period with pregnancy were compared to a period without pregnancy. Results: In ADPKD patients, a higher annualized liver cyst growth rate was observed during a period with pregnancy compared to a period without pregnancy (34 ± 16%/yr vs. 23 ± 17%/yr; p-value = 0.005). Liver volume growth was also higher during a period with pregnancy, 6 [2, 7]%/yr vs. 0.3 [−0.4, 2]%/yr (p-value = 0.04). In addition, the mean kidney cyst growth rate was higher (12 ± 11%/yr vs. 4 ± 9%/yr; p-value = 0.05), and there was a trend toward a pregnancy-associated increase in the TKV growth rate (6 [4, 8]%/yr vs. 3 [0.8, 5]%/yr, (p-value = 0.14) during a period with pregnancy. Conclusions: In patients with ADPKD, the liver volume and cyst volume growth rates increased during pregnancy. This supports the hypothesis that the estrogen-mediated stimulation of liver cyst growth may contribute to the severe polycystic liver disease that is more prevalent in women than men with ADPKD. Further studies with larger populations are needed to explore the mechanisms and long-term implications of these findings. Full article

Improper car tire pressure affects dynamics, fuel economy, and driver safety. Current central tire inflation systems (CTISs) regulate tire pressure relative to its reference value. However, the current CTIS is limited in its automation, as the system requires the loading of present conditions and the manual input of terrain conditions. Therefore, the system lacks intelligent components which would increase its efficiency. Adding a terrain recognition feature to the current CTIS technology, the tire pressure management system (TPMS) described in this paper enhances the capability to adjust to the ideal tire pressure according to the terrain condition. In this study, we integrate a terrain recognition component which uses a convolutional neural network (CNN), specifically, ResNet-18, into the TPMS to classify and detect terrain conditions and apply the correct pressure level. A one-tire terrain-based TPMS model was developed through system integration. The system was tested under flat, uneven, and soft terrain conditions. The CNN model demonstrated 95% accuracy in classifying the chosen terrains, with demonstrated adaptability to nighttime environments. Inflation and deflation tests were conducted at varying speeds and terrains, and the results showed longer inflation times at higher pressure ranges, while deflation times remained consistent regardless of pressure range. A negligible impact on inflation and deflation speed was observed at speeds below 15 km/h. Instantaneous response time between the microcontrollers increases efficiency in the overall CTIS process. Full article

Incorrect vehicle tire pressure affects vehicle dynamics, fuel efficiency, and driver safety across different terrain conditions. The current central tire inflation system (CTIS) alleviates this issue by adjusting the tire pressure to a predetermined reference level. However, the existing CTIS only adjusts the pressure based on load conditions through manual input for terrain types and lacks advanced intelligence for optimal automation. Integrating the recognition result of terrain conditions enables real-time adjustments of tire pressure and enhances driving performance and efficiency. This study aims to integrate the terrain recognition component using a convolutional neural network (CNN) by reviewing previous terrain-detection models. The CTIS was enhanced to classify and detect terrain conditions and apply the correct tire pressure level. We employed a systematic literature review (SLR) to assess the development procedures for integrating the intelligent component with the basic CTIS. ResNet-18 was used as the most appropriate CNN model to classify the terrain conditions on a gathered local dataset. A single-wheel testbed using the enhanced CTIS is appropriate for laboratory testing and system integration tests. Full article