iBCS: 4. Application of the Inhalation Biopharmaceutics Classification System to the Development of Orally Inhaled Drug Products.

This is the fourth paper in a series describing an inhalation biopharmaceutics classification system (iBCS), an initiative supported by the Product Quality Research Institute. The paper examines the application of the inhalation Biopharmaceutics Classification System (iBCS) through the drug discovery, development, and postapproval phases for orally inhaled drug products (OIDP) and for the development of generic OIDPs. We consider the implication of the iBCS class in terms of product performance and identify the practical gaps that must be filled to enable the classification system to be adopted into day-to-day practice.

Shifting boundaries, extended minds: ambient technology and extended allostatic control.

This article applies the thesis of the extended mind to ambient smart environments. These systems are characterised by an environment, such as a home or classroom, infused with multiple, highly networked streams of smart technology working in the background, learning about the user and operating without an explicit interface or any intentional sensorimotor engagement from the user. We analyse these systems in the context of work on the "classical" extended mind, characterised by conditions such as "trust and glue" and phenomenal transparency, and find that these conditions are ill-suited to describing our engagement with ambient smart environments.

Material culture both reflects and causes human cognitive evolution.

Our commentary suggests that different materialities (fragile, enduring, and mixed) may influence cognitive evolution. Building on Stibbard-Hawkes, we propose that predictive brains minimise errors and seek information, actively structuring environments for epistemic benefits. This perspective complements Stibbard-Hawkes' view.

Hacking the Predictive Mind.

According to active inference, constantly running prediction engines in our brain play a large role in delivering all human experience. These predictions help deliver everything we see, hear, touch, and feel. In this paper, I pursue one apparent consequence of this increasingly well-supported view.

Active inference goes to school: the importance of active learning in the age of large language models.

Human learning essentially involves embodied interactions with the material world. But our worlds now include increasing numbers of powerful and (apparently) disembodied generative artificial intelligence (AI). In what follows we ask how best to understand these new (somewhat 'alien', because of their disembodied nature) resources and how to incorporate them in our educational practices.

Measurements of Thermal Resistance Across Buried Interfaces with Frequency-Domain Thermoreflectance and Microscale Confinement.

Confined geometries are used to increase measurement sensitivity to thermal boundary resistance at buried SiO interfaces with frequency-domain thermoreflectance (FDTR). We show that radial confinement of the transducer film and additional underlying material layers prevents heat from spreading and increases the thermal penetration depth of the thermal wave. Parametric analyses are performed with finite element methods and used to examine the extent to which the thermal penetration depth increases as a function of a material's effective thermal resistance and the degree of material confinement relative to the pump beam diameter.

Digital Being: social media and the predictive mind.

Social media is implicated today in an array of mental health concerns. While concerns around social media have become mainstream, little is known about the specific cognitive mechanisms underlying the correlations seen in these studies or why we find it so hard to stop engaging with these platforms when things obviously begin to deteriorate for us. New advances in computational neuroscience, however, are now poised to shed light on this matter.

Cultivating creativity: predictive brains and the enlightened room problem.

How can one conciliate the claim that humans are uncertainty minimizing systems that seek to navigate predictable and familiar environments with the claim that humans can be creative? We call this the Enlightened Room Problem (ERP). The solution, we suggest, lies not (or not only) in the error-minimizing brain but in the environment itself. Creativity emerges from various degrees of interplay between predictive brains and changing environments: ones that repeatedly move the goalposts for our own error-minimizing machinery.

iBCS: 3. A Biopharmaceutics Classification System for Orally Inhaled Drug Products.

In this article, we specify for the first time a quantitative biopharmaceutics classification system for orally inhaled drugs. To date, orally inhaled drug product developers have lacked a biopharmaceutics classification system like the one developed to navigate the development of immediate release of oral medicines. Guideposts for respiratory drug discovery chemists and inhalation product formulators have been elusive and difficult to identify due to the complexity of pulmonary physiology, the intricacies of drug deposition and disposition in the lungs, and the influence of the inhalation delivery device used to deliver the drug as a respirable aerosol.

Generating meaning: active inference and the scope and limits of passive AI.

Prominent accounts of sentient behavior depict brains as generative models of organismic interaction with the world, evincing intriguing similarities with current advances in generative artificial intelligence (AI). However, because they contend with the control of purposive, life-sustaining sensorimotor interactions, the generative models of living organisms are inextricably anchored to the body and world. Unlike the passive models learned by generative AI systems, they must capture and control the sensory consequences of action.

Differential effect of lactate on synovial fibroblast and macrophage effector functions.

Introduction: The synovial membrane is the main site of inflammation in rheumatoid arthritis (RA). Here several subsets of fibroblasts and macrophages, with distinct effector functions, have been recently identified. The RA synovium is hypoxic and acidic, with increased levels of lactate as a result of inflammation.

The effect of polymer stiffness on magnetization reversal of magnetorheological elastomers.

Ultrasoft magnetorheological elastomers (MREs) offer convenient real-time magnetic field control of mechanical properties that provides a means to mimic mechanical cues and regulators of cells . Here, we systematically investigate the effect of polymer stiffness on magnetization reversal of MREs using a combination of magnetometry measurements and computational modeling. Poly-dimethylsiloxane-based MREs with Young's moduli that range over two orders of magnitude were synthesized using commercial polymers Sylgard 527, Sylgard 184, and carbonyl iron powder.

Extended active inference: Constructing predictive cognition beyond skulls.

Cognitive niche construction is the process whereby organisms create and maintain cause-effect models of their niche as guides for fitness influencing behavior. Extended mind theory claims that cognitive processes extend beyond the brain to include predictable states of the world. Active inference and predictive processing in cognitive science assume that organisms embody predictive (i.

iBCS: 2. Mechanistic Modeling of Pulmonary Availability of Inhaled Drugs versus Critical Product Attributes.

This work is the second in a series of publications outlining the fundamental principles and proposed design of a biopharmaceutics classifications system for inhaled drugs and drug products (the iBCS). Here, a mechanistic computer-based model has been used to explore the sensitivity of the primary biopharmaceutics functional output parameters: (i) pulmonary fraction dose absorbed () and (ii) drug half-life in lumen () to biopharmaceutics-relevant input attributes including dose number (Do) and effective permeability (). Results show the nonlinear sensitivity of primary functional outputs to variations in these attributes.

iBCS: 1. Principles and Framework of an Inhalation-Based Biopharmaceutics Classification System.

For oral drugs, the formulator and discovery chemist have a tool available to them that can be used to navigate the risks associated with the selection and development of immediate release oral drugs and drug products. This tool is the biopharmaceutics classification system (giBCS). Unfortunately, no such classification system exists for inhaled drugs.

The potential cost-effectiveness of HPV vaccination among girls in Mongolia.

Introduction: Cervical cancer is a leading cause of cancer among women in Mongolia with an age-standardized incidence rate of 23.5 per 100,000. HPV vaccination has not been introduced nationally and Gavi co-financing support is not available in Mongolia.

The Acquisition of Culturally Patterned Attention Styles Under Active Inference.

This paper presents an active inference based simulation study of visual foraging. The goal of the simulation is to show the effect of the acquisition of culturally patterned attention styles on cognitive task performance, under active inference. We show how cultural artefacts like antique vase decorations drive cognitive functions such as perception, action and learning, as well as task performance in a simple visual discrimination task.

Magnetic field tuning of mechanical properties of ultrasoft PDMS-based magnetorheological elastomers for biological applications.

We report tuning of the moduli and surface roughness of magnetorheological elastomers (MREs) by varying applied magnetic field. Ultrasoft MREs are fabricated using a physiologically relevant commercial polymer, Sylgard 527, and carbonyl iron powder (CIP). We found that the shear storage modulus, Young's modulus, and root-mean-square surface roughness are increased by ~41×, ~11×, and ~11×, respectively, when subjected to a magnetic field strength of 95.

Dynamic Tuning of Viscoelastic Hydrogels with Carbonyl Iron Microparticles Reveals the Rapid Response of Cells to Three-Dimensional Substrate Mechanics.

Current methods to dynamically tune three-dimensional hydrogel mechanics require specific chemistries and substrates that make modest, slow, and often irreversible changes in their mechanical properties, exclude the use of protein-based scaffolds, or alter the hydrogel microstructure and pore size. Here, we rapidly and reversibly alter the mechanical properties of hydrogels consisting of extracellular matrix proteins and proteoglycans by adding carbonyl iron microparticles (MPs) and applying external magnetic fields. This approach drastically alters hydrogel mechanics: rheology reveals that application of a 4000 Oe magnetic field to a 5 mg/mL collagen hydrogel containing 10 wt % MPs increases the storage modulus from approximately 1.

Damaged hardmen: Organized crime and the half-life of deindustrialization.

Despite frequent associations, deindustrialization features rarely in studies of organized crime, and organized crime is at best a spectral presence in studies of deindustrialization. By developing an original application of Linkon's concept of the "half-life," we present an empirical case for the symbiotic relationship between former sites of industry and the emergence of criminal markets. Based on a detailed case-study in the west of Scotland, an area long associated with both industry and crime, the paper interrogates the environmental, social, and cultural after-effects of deindustrialization at a community level.

Representation Wars: Enacting an Armistice Through Active Inference.

Over the last 30 years, representationalist and dynamicist positions in the philosophy of cognitive science have argued over whether neurocognitive processes should be viewed as representational or not. Major scientific and technological developments over the years have furnished both parties with ever more sophisticated conceptual weaponry. In recent years, an enactive generalization of predictive processing - known as active inference - has been proposed as a unifying theory of brain functions.

Magneto-Driven Gradients of Diamagnetic Objects for Engineering Complex Tissues.

Engineering complex tissues represents an extraordinary challenge and, to date, there have been few strategies developed that can easily recapitulate native-like cell and biofactor gradients in 3D materials. This is true despite the fact that mimicry of these gradients may be essential for the functionality of engineered graft tissues. Here, a non-traditional magnetics-based approach is developed to predictably position naturally diamagnetic objects in 3D hydrogels.