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Quantifying Return on Investment of Differentiating Technologies in Drug Development: A Decision Analytics FrameworkNARA Subscribed
Purpose Integrating differentiating technologies into drug development offers the potential for improved clinical outcomes and commercial success, but these benefits must be weighed against added cost, time, and risk. This study introduces a decision analytics framework that quantifies how technology integration influences key development variables and return on investment (ROI). Methods Leveraging real‑world datasets, risk-ad...
Optimizing Subcutaneous Antibody Dosing Regimens Through Operating Space Maps: rHuPH20 Case StudyNARA Subscribed
Therapeutic antibody dosing regimens are often constrained by formulation and administration factors that limit flexibility in dose and schedule. Subcutaneous (SC) delivery offers advantages over intravenous (IV) administration—such as improved convenience and potentially more favorable pharmacokinetic (PK) profiles—but is typically restricted by injection volume, requiring lower doses and more frequent dosing. Recombinant hum...
Effects of Pig Slurry Treatment with a Peroxide-Based Additive, GasAbate, on the Seasonal Growth of Perennial RyegrassNARA Subscribed
Livestock manures are valuable sources of crop nutrients, however greenhouse gas (GHG) emissions during storage exacerbate climate change and also preclude the closing of nutrient loops. Chemical additives applied during storage can reduce these emissions, where a peroxide-based slurry additive (GasAbate) successfully reduces GHG emissions from stored pig slurry. However, its effects upon crop uptake, and thus plant yields, fo...
Population Genomics of a Cosmopolitan Weed Provides Insights Into Its Local Adaptation and Recent Demographic HistoryNARA Subscribed
Invasive plant species present a growing ecological and economic challenge, and often adapt rapidly to their novel environments through complex demographic and evolutionary processes. Invasion genomics offers powerful tools to disentangle these processes, but most studies rely on geographically narrow sampling across native and non‐native ranges. Erigeron canadensis is a cosmopolitan weed native to North America that has succe...
Interpretable deep learning reveals spatiotemporal MRI features of brain aging that align with neurodegenerationNARA Subscribed
Cortical thinning and atrophy are hallmarks of brain aging that have been characterized using magnetic resonance imaging (MRI). Brain aging involves many neuroanatomic features whose effects on brain structure remain unexplored. To address this challenge, we trained interpretable deep neural networks (DNNs) to estimate brain age (BA) from T 1 -weighted ( T 1 w) MRI. By identifying MRI features unapparent to humans, DNNs can fi...
Alzheimer’s disease (AD) disproportionately affects women and carriers of the apolipoprotein E ε4 allele (APOE4), yet little is known about how sex and APOE interact to influence white matter (WM) integrity during disease progression. We integrated diffusion MRI and matched blood transcriptomic data to investigate these interactions and their underlying biological mechanisms. WM microstructure was quantified using diffusion te...
Prediction of bone ingrowth into the porous swelling bone anchors using an osteoconnectivity-based adaptive finite element algorithmNARA Subscribed
In this study, a bone ingrowth framework was developed, which was integrated with a hygro-elastic swelling simulation, to evaluate the ingrowth of bone into porous co-polymeric swelling bone anchors. The aim was to investigate the impact of swelling-induced radial stress on bone ingrowth and the improvement in the mechanical properties and fixation strength of the anchors. Using the finite element method coupled with the osteo...
Predicting the progression of MCI and Alzheimer’s disease on structural brain integrity and other features with machine learningNARA Subscribed
Machine learning (ML) on structural MRI data shows high potential for classifying Alzheimer’s disease (AD) progression, but the specific contribution of brain regions, demographics, and proteinopathy remains unclear. Using Alzheimer’s Disease Neuroimaging Initiative (ADNI) data, we applied an extreme gradient-boosting algorithm and SHAP (SHapley Additive exPlanations) values to classify cognitively normal (CN) older adults, th...
Extreme Drought Increases the Temporal Variability of Grassland Productivity by Suppressing Dominant GrassesNARA Subscribed
Extreme droughts are intensifying, yet their impact on temporal variability of grassland functioning and its drivers remains poorly understood. We imposed a 6‐year extreme drought in two semiarid grasslands to explore how drought influences the temporal variability of ANPP and identify potential stabilising mechanisms. Drought decreased ANPP while increasing its temporal variability across grasslands. In the absence of drought...
Recent increases in frequency and intensity of warm water anomalies and marine heatwaves have led to shifts in species ranges and assemblages. Genomic tools can be instrumental in detecting such shifts. In the early stages of a project assessing population genetic structure in Pacific Sardine ( Sardinops sagax ), we detected the presence of Japanese Sardine ( Sardinops melanosticta ) along the west coast of North America for t...
Defining an ageing-related pathology, disease or syndrome: International Consensus StatementNARA Subscribed
Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndrom...
Co-production of models to evaluate conservation alternatives for a threatened fish in a rapidly changing landscapeNARA Subscribed
Reintroductions are one means of managing species distributions, but the feasibility of such efforts is uncertain. Here we consider reintroduction for threatened bull trout ( Salvelinus confluentus ) that currently occupy a small fraction of historically occupied habitats in the upper Klamath River basin owing to climate warming and human modifications of ecosystems. We engaged stakeholders across multiple organizations to co-...