Validation of Risk Prediction Models for Pneumothorax and Intercostal Catheter Insertion Following CT-Guided Lung Biopsy.

Background: CT-guided percutaneous transthoracic needle biopsy is the primary method for diagnosing lung lesions. Widely accepted validated risk prediction models are yet to be developed. A recently published study conducted at Grampians Health Services (GHS) developed two risk prediction models for predicting pneumothorax and intercostal catheter (ICC) insertion.

Divergent Molecular Pathways for Toxicity of Selected Mutant C9ORF72-derived Dipeptide Repeats.

Expansion of a hexanucleotide repeat in a noncoding region of the C9ORF72 gene is responsible for a significant fraction of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) cases, but mechanisms linking mutant gene products to neuronal toxicity remain debatable. Pathogenesis was proposed to involve the production of toxic RNA species and/or accumulation of toxic dipeptide repeats (DPRs) but distinguishing between these mechanisms has been challenging. In this study, we first use complementary model systems for analyzing pathogenesis in adult-onset neurodegenerative diseases to characterize the pathogenicity of DPRs produced by Repeat Associated Non-ATG translation of C9ORF72 in specific cellular compartments: isolated axoplasm and giant synapse from the squid.

Creating the Pick's disease International Consortium: Association study of H2 haplotype with risk of Pick's disease.

Background: Pick's disease (PiD) is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. PiD is pathologically defined by argyrophilic inclusion Pick bodies and ballooned neurons in the frontal and temporal brain lobes. PiD is characterised by the presence of Pick bodies which are formed from aggregated, hyperphosphorylated, 3-repeat tau proteins, encoded by the gene.

Integrating peer support services into primary care-based OUD treatment: Lessons from the Penn integrated model.

Opioid use disorder (OUD) is a major public health emergency in the United States. In 2020, 2.7 million individuals had an OUD.

Regional variability and genotypic and pharmacodynamic effects on PrP concentration in the CNS.

Prion protein (PrP) concentration controls the kinetics of prion replication and is a genetically and pharmacologically validated therapeutic target for prion disease. In order to evaluate PrP concentration as a pharmacodynamic biomarker and assess its contribution to known prion disease risk factors, we developed and validated a plate-based immunoassay reactive for PrP across 6 species of interest and applicable to brain and cerebrospinal fluid (CSF). PrP concentration varied dramatically across different brain regions in mice, cynomolgus macaques, and humans.

BMAA, Methylmercury, and Mechanisms of Neurodegeneration in Dolphins: A Natural Model of Toxin Exposure.

Dolphins are well-regarded sentinels for toxin exposure and can bioaccumulate a cyanotoxin called β--methylamino-l-alanine (BMAA) that has been linked to human neurodegenerative disease. The same dolphins also possessed hallmarks of Alzheimer's disease (AD), suggesting a possible association between toxin exposure and neuropathology. However, the mechanisms of neurodegeneration in dolphins and the impact cyanotoxins have on these processes are unknown.

Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.

Alzheimer's disease (AD) causes unrelenting, progressive cognitive impairments, but its course is heterogeneous, with a broad range of rates of cognitive decline. The spread of tau aggregates (neurofibrillary tangles) across the cerebral cortex parallels symptom severity. We hypothesized that the kinetics of tau spread may vary if the properties of the propagating tau proteins vary across individuals.

Assessment of Machine Learning vs Standard Prediction Rules for Predicting Hospital Readmissions.

Importance: Hospital readmissions are associated with patient harm and expense. Ways to prevent hospital readmissions have focused on identifying patients at greatest risk using prediction scores.

Objective: To identify the type of score that best predicts hospital readmissions.

Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain.

Alzheimer's disease (AD) is defined by the presence of intraneuronal neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several and studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a "prion-like" spread of tau aggregates may be an underlying cause of Braak tau staging in AD.

Tau reduction in the presence of amyloid-β prevents tau pathology and neuronal death in vivo.

Several studies have now supported the use of a tau lowering agent as a possible therapy in the treatment of tauopathy disorders, including Alzheimer's disease. In human Alzheimer's disease, however, concurrent amyloid-β deposition appears to synergize and accelerate tau pathological changes. Thus far, tau reduction strategies that have been tested in vivo have been examined in the setting of tau pathology without confounding amyloid-β deposition.

Effect of eddy length scale on mechanical loading of blood cells in turbulent flow.

Non-physiological turbulent blood flow is known to occur in and near implanted cardiovascular devices, but its effects on blood are poorly understood. The objective of this work is to investigate the effect of turbulent eddy length scale on blood cell damage, and in particular to test the hypothesis that only eddies similar in size to blood cells can cause damage. The microscale flow near a red blood cell (RBC) in an idealized turbulent eddy is modeled computationally using an immersed boundary method.

Models of flow-induced loading on blood cells in laminar and turbulent flow, with application to cardiovascular device flow.

Viscous shear stress and Reynolds stress are often used to predict hemolysis and thrombosis due to flow-induced stress on blood elements in cardiovascular devices. These macroscopic stresses are distinct from the true stress on an individual cell, which is determined by the local microscale flow field. In this paper the flow-induced stress on blood cells is calculated for laminar and turbulent flow, using simplified models for cells and for turbulent eddies.

Optically timed submillimeter time-of-flight mass spectrometry.

We demonstrate that using intense femtosecond laser pulses to optically time ion flight can lead to a miniature time-of-flight mass spectrometer. After laser ionization, the molecular ion is accelerated by a static electric field and detected using a second, delayed laser pulse. The relative positions of the two laser foci determine the ion flight distance while the time separation of the laser pulses fixes the ion flight time.