Unsupervised Dimensionality Reduction Techniques for the Assessment of ASD Biomarkers.

Autism Spectrum Disorder (ASD) encompasses a range of developmental disabilities marked by differences in social functioning, cognition, and behavior. Both genetic and environmental factors are known to contribute to ASD, yet the exact etiological factors remain unclear. Developing integrative models to explore the effects of gene expression on behavioral and cognitive traits attributed to ASD can uncover environmental and genetic interactions.

Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. A specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual's brain affected by their unique white matter hyperintensity location and volume.

Exploration of the potential impact of batch-to-batch variability on the establishment of pharmacokinetic bioequivalence for inhalation powder drug products.

Batch-to-batch variability in inhalation powder has been identified as a potential challenge in the development of generic versions. This study explored the impact of batch-to-batch variability on the probability of establishing pharmacokinetic (PK) bioequivalence (BE) in a two-sequence, two-period (2 × 2) crossover study. A model-based parametric simulation approach was employed, incorporating batch-to-batch variability through the relative bioavailability (RBA) ratio.

A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium.

Adapting a Preparatory Skills-Building Programme for Carers of People With Cancer Through Co-Design: The iCanSupport Project.

Introduction: Health services rely upon carers to provide care for loved ones with cancer, yet many carers often feel ill-prepared for this role. Despite a multitude of programmes to support carer mental health, programmes that help carers feel better equipped to support a person with cancer are lacking. This study aimed to address this need by adapting an evidence-based intervention to be suitable for carers of people with cancer.

Microstructural Characterization of Dry Powder Inhaler Formulations Using Orthogonal Analytical Techniques.

Purpose: For locally-acting dry powder inhalers (DPIs), developing novel analytical tools that are able to evaluate the state of aggregation may provide a better understanding of the impact of material properties and processing parameters on the in vivo performance. This study explored the utility of the Morphologically-Directed Raman Spectroscopy (MDRS) and dissolution as orthogonal techniques to assess microstructural equivalence of the aerosolized dose of DPIs collected with an aerosol collection device.

Methods: Commercial DPIs containing different strengths of Fluticasone Propionate (FP) and Salmeterol Xinafoate (SX) as monotherapy and combination products were sourced from different regions.

Anatomically-detailed segmented representative adult and pediatric nasal models for assessing regional drug delivery and bioequivalence with suspension nasal sprays.

In vitro nasal models can potentially facilitate development and approval of nasal drug products. This study aims to evaluate the potential for using regional deposition measurements from in vitro nasal models to evaluate nasal spray performance across several products. To accomplish this, the posterior regions of six anatomically realistic nasal airway models of adult and pediatric subjects, representing Low (L), Mean (M) and High (H) posterior drug deposition (PD) for each of the two age groups, were segmented with high anatomical precision into five regions of interest.

Review article: Strategies to improve emergency department care for adults living with disability: A systematic review.

Equitable access means that timely, sensitive and respectful treatment is offered to all people. Adults with disability access ED care more frequently than the general population. However, in Australia and internationally, people with disability experience poorer healthcare access and outcomes than the general population.

Child life specialists predict successful MRI scanning in unsedated children 4 to 12 years old.

Background: It can be challenging for children to cooperate for a magnetic resonance imaging (MRI) exam. General anesthesia is often used to ensure a high-quality image. When determining the need for general anesthesia, many institutions use a simple age cutoff.

Widespread Associations between Behavioral Metrics and Brain Microstructure in ASD Suggest Age Mediates Subtypes of ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors. Our lab has previously found that g-ratio, the proportion of axon width to myelin diameter, and axonal conduction velocity, which is associated with the capacity of an axon to carry information, are both decreased in ASD individuals. By associating these differences with performance on cognitive and behavioral tests, this study aims to first associate a broad array of behavioral metrics with neuroimaging markers of ASD, and to explore the prevalence of ASD subtypes using a neuroimaging driven perspective.

Supporting Carers: Study Protocol of a Meta-Review of Psychosocial Interventions for Carers of People With Cancer.

Background: While there is a clear need for psychosocial interventions that promote the well-being of carers of patients with cancer, the corresponding evidence base is disparate, complex, and difficult for end users to navigate and interpret. Carers remain undersupported with a lack of dedicated, effective, evidence-based programs. We will conduct a meta-review to synthesize this evidence and determine the state of science in this field.

CFD-PK model for nasal suspension sprays: Validation with human adult in vivo data for triamcinolone acetonide.

The objectives of this study were to expand and implement a Computational Fluid Dynamics (CFD)-Dissolution, Absorption and Clearance (DAC)-Pharmacokinetics (PK) multi-physics modeling framework for simulating the transport of suspension-based nasal corticosteroid sprays. The mean CFD-predicted peak plasma concentration (C) and area under the curve (AUC) of the plasma concentration-time profile, based on three representative nasal airway models (capturing low, medium and high posterior spray deposition), were within one standard deviation of available in vivo PK data for a representative corticosteroid drug (triamcinolone acetonide). The relative differences in mean C between predictions and in vivo data for low dose (110 µg) and high dose (220 µg) cases were 27.

Angioedema Secondary to Tenecteplase Use in a Patient with Acute Ischemic Stroke: A Case Report.

Introduction: Angioedema, a swelling of the subcutaneous or submucosal layers of the skin or gastrointestinal tract, is a potential complication to thrombolytic therapy in the treatment of acute ischemic strokes. In these cases, angioedema develops due to increased levels of bradykinin as a result of the activation of the fibrinolytic pathway and contact activation system. Angioedema can involve the tongue, larynx, and vocal cords, leading to occlusion of the airway and death due to asphyxiation.

A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.

The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences.

Creating safer cancer care with ethnic minority patients: A qualitative analysis of the experiences of cancer service staff.

Introduction: Effective consumer engagement practices can enhance patient safety. This is important for consumers from ethnic minority backgrounds who are exposed to increased risk of patient safety events. Using the Systems Engineering Initiative for Patient Safety model, this study explored staff experiences of creating opportunities for engagement with consumers from ethnic minority backgrounds to contribute to their cancer care safety.

Assessment of Sports Concussion in Female Athletes: A Role for Neuroinformatics?

Over the past decade, the intricacies of sports-related concussions among female athletes have become readily apparent. Traditional clinical methods for diagnosing concussions suffer limitations when applied to female athletes, often failing to capture subtle changes in brain structure and function. Advanced neuroinformatics techniques and machine learning models have become invaluable assets in this endeavor.

Emergency department management of patients with sickle cell disease.

Sickle cell disease is a chronic hematologic disease that affects over 100,000 people in the United States. Many of these patients will present to the emergency department seeking treatment for an acute complication. Vaso-occlusive crisis, the most common recurring complication, can be difficult to manage because of the stigma patients face surrounding management of their pain.

AQUA-GAPS/MONET-Derived Concentrations and Trends of PAHs and Polycyclic Musks across Global Waters.

Polycyclic aromatic hydrocarbons (PAHs), released from petrogenic, pyrogenic or diagenetic sources (degradation of wood materials), are of global concern due to their adverse effects, and potential for long-range transport. While dissolved PAHs have been frequently reported in the literature, there has been no consistent approach of sampling across water bodies. Passive samplers from the AQUA/GAPS-MONET initiative were deployed at 46 sites (28 marine and 18 freshwater), and analyzed for 28 PAHs and six polycyclic musks (PCMs) centrally.

Engaging With Health Consumers in Scientific Conferences-As Partners not Bystanders.

Introduction: It is now widely recognised that engaging consumers in research activities can enhance the quality, equity and relevance of the research. Much of the commentary about consumer engagement in research focuses on research processes and implementation, rather than dissemination in conference settings. This article offers reflections and learnings from consumers, researchers and conference organisers on the 12th Health Services Research Conference, a biennial conference hosted by the Health Services Research Association of Australia and New Zealand (HSRAANZ).

Occurrence and potential hazard posed by pharmaceutically active compounds in coastal waters in Cape Town, South Africa.

The occurrence of 58 pharmaceutically active compounds (PhACs) in surface water at 28 coastal and five river sites, and in two stormwater flows in Cape Town, South Africa, was investigated in winter and summer. After accounting for quality assurance and control data, 33 PhACs were considered in detail. In winter, 25 PhACs were found at one or more sites and 27 in summer.

Measuring Healthcare Experiences Among People With Intellectual Disability: A Rapid Evidence Synthesis of Tools and Methods.

Objectives: Patient-reported experience measures (PREMs) collect essential data for service and system-wide quality improvement and performance monitoring toward value-based care. However, the experiences of people with intellectual disability, who have high healthcare utilization couple with poorer outcomes, are often omitted from system-wide PREMs and service-wide PREMs data. The use of PREMs instruments for data collection among people with intellectual disability has not been explored.

Pharmacokinetic Models for Inhaled Fluticasone Propionate and Salmeterol Xinafoate to Quantify Batch-to-Batch Variability.

Advair Diskus is an essential treatment for asthma and chronic obstructive pulmonary disease. It is a dry powder inhaler with a combination of fluticasone propionate (FP) and salmeterol xinafoate (SX). However, the pharmacokinetics (PK) batch-to-batch variability of the reference-listed drug (RLD) hindered its generic product development.

Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information.

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

Objectives: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS.

Delays in the diagnosis and surgical treatment of drug-resistant epilepsy: A cohort study.

Objective: Delay in referral for epilepsy surgery of patients with drug-resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.