Search

Wide-field magneto-optic Kerr observation techniques are described for the imaging of magnetic recording heads and other small magnetic devices. The imaging problems encountered for these samples are quite different from those for continuous films and lead to a different set of experimental approaches. Observation techniques that preserve the magnetic state of the sample allow for the implementation of new image acquisition algorithms based on multiple additions and subtractions that progressively build up a weak Kerr contrast even under unfavorable experimental conditions. Examples of results are presented.

We report on a newly discovered domain configuration, observed with a magneto-optical microscope, in narrow stripes of NiCoFe, CoFeCu and NiFe. The stripes - 1 to 25 micrometers wide and 0.5 to 2.0 micrometers thick - are used here as a model for a narrow-track pole of a recording head. The new domain configuration, with its magnetization oriented mostly in a plane perpendicular to the long dimension of the stripe, suggests the possibility of obtaining a large high-frequency susceptibility even in recording head poles as narrow as 1 micrometer.

Describes a laser magneto-optic (LAMOM) system used to observe magnetic domains in Permalloy thin-film devices. Methods by which background suppression has been accomplished to obtain high-contrast images of magnetic domains; Description of the LAMOM system; Types of illumination used in the experiment.

Presents a study which investigated the domain response in square and near-square-shaped permalloy films through laser magneto-optic microscope. Process of magnetization between domains of a ferromagnetic body; Behavior of the wall structure in a thick square permalloy film; Discussion on domain magnetization prior to bifurcation.

Presents a study which described a dynamic response behavior of domain walls in the permalloy of thin-film inductive heads. Method of the study; Results and discussion; Conclusion.

Describes a dynamic response behavior of domain walls in the permalloy of thin-film inductive heads. Use of the laser magneto-optic microscope; Information on the direction of the dynamic wall displacements.

Focuses on the proposed laminated Permalloys to increase permeability and reduce wall noise in recording. Microscope used to study inductive-head-yoke shaped elements of Permalloy layers separated by nonmagnetic metallic spacers; Description of the transients seen during the transition from a one-wall to a no-wall state; Explanation for the difference between the coupled states of four-layer elements and two-layer elements.

Background: Medications for comorbid conditions may affect cognition in Alzheimer's disease (AD)., Objective: To explore the association between common medications and cognition, measured with the Mini-Mental State Examination., Methods: Cohort study including persons with AD from the Swedish Registry for Cognitive/Dementia Disorders (SveDem). Medications were included if they were used by ≥5% of patients (26 individual drugs). Each follow-up was analyzed independently by performing 100 Monte-Carlo simulations of two steps each 1) k-means clustering of patients according to Mini-Mental State Examination at follow-up and its decline since previous measure, and 2) Identification of medications presenting statistically significant differences in the proportion of users in the different clusters., Results: 15,428 patients (60.38% women) were studied. Four clusters were identified. Medications associated with the best cognition cluster (relative to the worse) were atorvastatin (point estimate 1.44 95% confidence interval [1.15-1.83] at first follow-up, simvastatin (1.41 [1.11-1.78] at second follow-up), warfarin (1.56 [1.22-2.01] first follow-up), zopiclone (1.35 [1.15-1.58], and metformin (2.08 [1.35-3.33] second follow-up. Oxazepam (0.60 [0.50-0.73] first follow-up), paracetamol (0.83 [0.73-0.95] first follow-up), cyanocobalamin, felodipine and furosemide were associated with the worst cluster. Cholinesterase inhibitors were associated with the best cognition clusters, whereas memantine appeared in the worse cognition clusters, consistent with its indication in moderate to severe dementia., Conclusions: We performed unsupervised clustering to classify patients based on their current cognition and cognitive decline from previous testing. Atorvastatin, simvastatin, warfarin, metformin, and zopiclone presented a positive and statistically significant associations with cognition, while oxazepam, cyanocobalamin, felodipine, furosemide and paracetamol, were associated with the worst cluster., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hot-melt extrusion (HME) is a widely used method for creating amorphous solid dispersions (ASDs) of poorly soluble drug substances, where the drug is molecularly dispersed in a solid polymer matrix. This study examines the impact of three different copovidone excipients, their reactive impurity levels, HME barrel temperature, and the distribution of colloidal silicon dioxide (SiO 2 ) on impurity levels, stability, and drug release of ASDs and their tablets. Initial peroxide levels were higher in Kollidon VA 64 (KVA64) and Plasdone S630 (PS630) compared to Plasdone S630 Ultra (PS630U), leading to greater oxidative degradation of the drug in fresh ASD tablets. However, stability testing (50 °C, closed container, 50 °C/30% RH, open conditions) showed lower oxidative degradation impurities in ASD tablets prepared at higher barrel temperatures, likely due to greater peroxide degradation. Plasdone S630 is suitable for ASDs with drugs prone to oxidative degradation, while standard purity grades may benefit drugs susceptible to free radical degradation, as they generate fewer free radicals post-HME. ASD tablets exhibited greater physical stability than milled extrudate samples, likely due to reduced exposure to stability conditions within the tablet matrix. Including SiO 2 in the extrudate composition resulted in greater physical stability of the ASD system in the tablet; however, it negatively affected chemical stability, promoting greater oxidative degradation and hydroxylation of the drug substance. No impact of the distribution of SiO 2 on drug release was observed. The study also confirmed the congruent release of copovidone, the drug substance, and Tween 80 using flow NMR coupled with in-line UV/vis. This research highlights the critical roles of peroxide levels and SiO 2 in influencing the dissolution and physical and chemical stability of ASDs. The findings provide valuable insights for developing stable and effective pharmaceutical formulations, emphasizing the importance of controlling reactive impurities and excipient characteristics in ASD products prepared by using HME.

Background: While World Rugby guidelines do not mandate the inclusion of an electrocardiogram (ECG) for all players, this is required for entry into international rugby competitions. We, therefore, sought to describe sport-specific normative ECG values and evaluate the performance of contemporary athlete ECG guidelines in male and female professional rugby players., Methods: We retrospectively analysed professional rugby players' ECGs (n=356, male 79%) obtained during preparticipation screening (2010-2022), comparing by sex and playing position (forwards vs backs). ECGs were categorised as normal 'training-related', borderline and abnormal findings, as defined by the 2017 International Recommendations., Results: 84% of players had one or more normal, 'training-related' findings, with males having a higher prevalence than females (91% vs 60%, p<0.001). Most ECG findings did not vary by position. No female player had borderline or abnormal ECG findings. Borderline findings were present in 3% (n=12/356) of players. Abnormal findings were present in 2% (n=7/356) of players. Overall, 2.2% of ECGs were 'positive' (n=8/356, including n=1 ECG with two borderline findings)., Conclusions: The application of contemporary ECG interpretation criteria resulted in a low positivity rate isolated to male players. These results help inform the logistic feasibility of ECG-inclusive screening, which is already required to enter major tournaments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer's disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms., Objective: To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment., Methods: A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users., Results: Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent., Conclusions: Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses., (© 2023. The Author(s).)

Background: While young adults 18-24 years old bear a significant proportion of COVID-19 diagnoses, the risk factors for hospitalisation and severe COVID-19 complications in this population are poorly understood., Objective: The objective of this study was to identify risk factors for hospitalisation and other COVID-19 complications across the health spectrum of young adults diagnosed with COVID-19 infection., Study Design: Retrospective cohort study., Participants: Young adults (aged 18-24) with confirmed COVID-19 infection from the American Heart Association (AHA) COVID-19 Cardiovascular Disease Registry of hospitalised patients and the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA) study of collegiate athletes. The AHA registry included 636 young adults from 152 hospitals. The ORCCA registry consisted of 3653 competitive college athletes from 42 colleges and universities., Intervention: None (exposure to COVID-19)., Primary and Secondary Outcome Measures: Main outcomes included hospitalisation, death, major adverse cardiovascular events (MACE) and other severe clinical events., Results: In comparison to the ORCCA registry, patients in the AHA registry were more likely to be female (59% vs 33%); had higher average body mass index (BMI) (32.4 vs 25.6); and had increased prevalence of diabetes (10% vs 0.4%), hypertension (7% vs 0.6%), chronic kidney disease (2% vs 0%) and asthma (14% vs 8%), all with p<0.01. There were eight (2%) deaths in the AHA hospitalised registry compared with zero in the ORCCA cohort. BMI was a statistically significant predictor of death in the hospitalised cohort (OR 1.05, 95% CI 1.00, 1.10). No significant predictors of MACE or other severe clinical events were identified., Conclusions: The risk of cardiac events in young adults aged 18-24 diagnosed with COVID-19 infection is low. Patients who were hospitalised (AHA registry) were more likely to have pre-existing medical comorbidities and higher BMI than healthy collegiate athletes (ORCCA registry). Once hospitalised, elevated BMI is associated with increased mortality although other drivers of MACE and other severe clinical events remain unclear., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The physiological properties of the gastrointestinal tract, such as pH, fluid volume, bile salt concentration, and gastrointestinal transit time, are highly variable in vivo. These properties can affect the dissolution and absorption of a drug, depending on its properties and formulation. The effect of gastrointestinal physiology on the bioperformance of a drug was studied in silico for a delayed-release pantoprazole tablet and an immediate-release dolutegravir tablet. Physiologically based absorption models were developed and virtual clinical trials were performed. Reasons for the variability in drug bioperformance between subjects were investigated, taking into account differences in gastrointestinal tract characteristics, pharmacokinetic parameters, and additional parameters (e.g., permeability). Default software parameters describing gastrointestinal physiology in the fasted and fed states, and variation in these parameters, were altered to match variability in these parameters reported in vivo. The altered model physiologies better described the variability of gastrointestinal conditions, and therefore the results of virtual trials using these physiologies are likely to be more relevant in vivo. With such altered gastrointestinal physiologies used to develop models, it is possible to obtain additional knowledge and improve the understanding of subject-formulation interactions., Competing Interests: Declarations of Interest None., (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The highly variable physiological conditions within the gastrointestinal tract can cause variable drug release and absorption from the orally administrated dosage forms. The emptying of the gastric content is one of the most critical physiological processes, dictating the amount of the active ingredient available for absorption into the systemic circulation. In this study, we prepared two water gastric emptying regimes on advanced gastric simulator (AGS) with programmable "pyloric" valve. Gastric emptying regimes were designed in such a way to capture the main findings of the MRI (magnetic resonance imaging) in vivo studies, conducted under fasted conditions according to the EMA and FDA guidelines for bioavailability and bioequivalence studies. Four immediate release formulations containing a model drug of BCS class III were tested. Comparative dissolution tests were also performed with the USP2 apparatus. In vitro release profiles were compared to the in vivo data in order to evaluate the importance of gastric emptying for subsequent absorption of the active substance from the tested formulations. Our bio-relevant in vitro dissolution model showed good discriminatory power for all of the tested formulations. Moreover, a better relation to in vivo data was achieved with AGS with respect to the tested conventional dissolution method., Competing Interests: Declaration of competing Interest The authors declared no conflicts of interest related to this article. The authors from University of Ljubljana, Faculty of Pharmacy were supported by the Slovenian Research Agency (ARRS) [P1-0189]., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Survival in patients with dementia is variable. Statins are a cornerstone of cardiovascular prevention. However, the effect of statins on mortality and risk for stroke in patients with dementia is not clear., Objective: The aim of the study was to analyse the association between the use of statins and the risk of all-cause death and first ischemic stroke in patients diagnosed with dementia., Methods: A longitudinal cohort study of 48 771 patients based on combined Swedish registries was conducted. The association between the incident use of statins one year prior to dementia diagnosis, allcause mortality and first ischemic stroke was examined using propensity score-matched flexible parametric or Cox hazard survival models and is presented with hazard ratios and corresponding 95% confidence intervals., Results: After propensity score matching, incident users of statins (n=1412) had a lower risk of all-cause death (HR 0.82, 95% CI 0.74-0.91) and ischemic stroke (HR 0.62, 95% CI 0.43-0.89) compared to matched non-users (n=4482). In stratified analysis, the protective association between incident statin use and survival was observed in men, patients older than 75 years, with Alzheimer's disease and vascular dementia. Furthermore, we observed a protective association between incident use of statins and first ischemic stroke risk in men, patients older than 75 years and with mixed dementia. There was a graded association between cumulative doses of statins and mortality., Conclusion: The use of statins might be beneficial for the survival and ischemic stroke risk in patients with dementia in a dose-dependent manner., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A physiologically based pharmacokinetic (PBPK) absorption model was developed in GastroPlus™ based on data on intravenous, immediate-release (IR), and modified-release (MR) drug products. The predictability of the model was evaluated by comparing predicted and observed plasma concentration profiles; average prediction errors (PE) were below 10%. IVIVR was developed using mechanistic deconvolution for a MR drug product to evaluate the in vivo effect of a proposed change in dissolution specification. The predictability of the IVIVR was evaluated and PE were below 10%; however, external validation was not possible due to the lack of data. The developed PBPK absorption model and IVIVR were used to predict plasma concentration profiles and pharmacokinetic (PK) parameters for a hypothetical formulation with 0% of drug dissolved in 2 h in in vitro dissolution test. Both methods predicted the insignificant effect of a change in in vitro dissolution profile on in vivo product performance. The bioequivalence of a hypothetical formulation to the test product was evaluated using virtual clinical trial. The performed analysis supported the proposed change in dissolution specification. A validated PBPK absorption model was proposed as an adequate alternative to IVIVC, when IVIVC could not have been developed according to the guidelines.