Generics and Quantified Generalizations: Asymmetry Effects and Strategic Communicators.

Generic statements ('Tigers have stripes') are pervasive and developmentally early-emerging modes of generalization with a distinctive linguistic profile. Previous experimental work suggests that generics display a unique asymmetry between the prevalence levels required to accept them and the prevalence levels typically implied by their use. This asymmetry effect is thought to have serious social consequences: if speakers use socially problematic generics based on prevalence levels that are systematically lower than what is typically inferred by their recipients, then using generics will likely exacerbate social stereotypes and biases.

Salient semantics.

Semantic features are components of concepts. In philosophy, there is a predominant focus on those features that are necessary (and jointly sufficient) for the application of a concept. Consequently, the method of cases has been the paradigm tool among philosophers, including experimental philosophers.

Physiologically Based Biopharmaceutics Modeling for Gefapixant IR Formulation Development and Defining the Bioequivalence Dissolution Safe Space.

Gefapixant is a weakly basic drug which has been formulated as an immediate release tablet for oral administration. A physiologically based biopharmaceutics model (PBBM) was developed based on gefapixant physicochemical properties and clinical pharmacokinetics to aid formulation selection, bioequivalence safe space assessment and dissolution specification settings. In vitro dissolution profiles of different free base and citrate salt formulations were used as an input to the model.

Effect of basket mesh size on the hydrodynamics of a partially filled (500 mL) USP rotating basket dissolution testing Apparatus 1.

The USP Rotating Basket Dissolution Testing Apparatus 1 is listed in the USP as one of the tools to assess dissolution of oral solid dosage forms. Baskets of different mesh sizes can be used to differentiate between dissolution profiles of different formulations. Here, we used Particle Image Velocimetry (PIV) to study the hydrodynamics of the USP Apparatus 1 using baskets with different mesh openings (10-, 20- and 40-mesh) revolving at 100 rpm, when the vessel was filled with 500 mL.

The ambiguity of "true" in English, German, and Chinese.

Through a series of empirical studies involving native speakers of English, German, and Chinese, this paper reveals that the predicate "true" is inherently ambiguous in the empirical domain. Truth statements such as "It is true that Tom is at the party" seem to be ambivalent between two readings. On the first reading, the statement means "Reality is such that Tom is at the party.

Evaluative Deflation, Social Expectations, and the Zone of Moral Indifference.

Acts that are considered undesirable standardly violate our expectations. In contrast, acts that count as morally desirable can either meet our expectations or exceed them. The zone in which an act can be morally desirable yet not exceed our expectations is what we call the zone of moral indifference, and it has so far been neglected.

Mutual entailment between causation and responsibility.

The standard view in philosophy is that responsibility entails causation. Most philosophers treat this entailment claim as an evident insight into the ordinary concepts of responsibility and causation. Further, it is taken to be equally obvious that the reversal of this claim does not hold: causation does not entail responsibility.

The varying rationality of weakness of the will: an empirical investigation and its challenges for a unified theory of rationality.

Weakness of the will remains a perplexing issue. Though philosophers have made substantial progress in homing in on what counts as a weak will, there is little agreement on whether weakness of the will is irrational, and if so, why. In this paper, we take an empirical approach towards the rationality of weakness of the will.

Influence of basket mesh size on the hydrodynamics in the USP rotating basket dissolution testing Apparatus 1.

The USP Apparatus 1 (rotating basket), typically used to assess drug product reproducibility and evaluate oral solid dosage forms performance, consists of a cylindrical glass vessel with a hemispherical bottom and a wire basket rotating at constant speed. Baskets with different wire openings can be used in alternative to the standard mesh opening (40-mesh) in order to discriminate between drug formulations during early stage of drug product development. Any changes introduced by different basket geometries can potentially and significantly impact the system hydrodynamics and cause variability of results, thus affecting product quality.

Incidence, Risk Factors and Impact on Long-Term Outcome of Postoperative Delirium After Transcatheter Aortic Valve Replacement.

The aim of the present study was to analyze incidence, risk factors, and association with long-term outcome of postoperative delirium (POD) after transcatheter aortic valve replacement (TAVR). Six hundred and sixty one consecutive patients undergoing TAVR were prospectively enrolled from January 2016 to December 2017. POD was assessed regularly during ICU-stay using the CAM-ICU test.

Biowaiver Applications in Support of a Polymorph During Late-Stage Clinical Development of Verubecestat-Current Challenges and Future Opportunities for Global Regulatory Alignment.

Dissolution experiments to support an active pharmaceutical ingredient (API) form change in Verubecestat immediate release tablets were performed following current regulatory guidance published by health authorities in Canada, Australia, Japan, the EU, and the USA. Verubecestat API meets the requirements of a Biopharmaceutics Classification System class 1 compound and tablets are very  rapidly dissolving in aqueous dissolution media. While the in vitro data were reviewed favorably by these agencies, the divergence in regulatory requirements led to unnecessary work and highlights several issues companies operating globally face to justify product changes that have very little impact on quality.

USP Apparatus 4: a Valuable In Vitro Tool to Enable Formulation Development of Long-Acting Parenteral (LAP) Nanosuspension Formulations of Poorly Water-Soluble Compounds.

Long-acting or extended release parenteral dosage forms have attracted extensive attention due to their ability to maintain therapeutic drug concentrations over long periods of time and reduce administration frequency, thus improving patient compliance. It is essential to have an in vitro release (IVR) testing method that can be used to assure product quality during routine production as well as predict and understand the in vivo performance of a formulation. The purpose of this work was to develop a discriminatory in vitro release method to guide formulation and process development of long-acting parenteral (LAP) nanosuspension formulations composed of poorly water-soluble drugs (BCS class II).

Mediating Passive Tumor Accumulation through Particle Size, Tumor Type, and Location.

As the enhanced permeation and retention (EPR) effect continues to be a controversial topic in nanomedicine, we sought to examine EPR as a function of nanoparticle size, tumor model, and tumor location, while also evaluating tumors for EPR mediating factors such as microvessel density, vascular permeability, lymphatics, stromal content, and tumor-associated immune cells. Tumor accumulation was evaluated for 55 × 60, 80 × 180, and 80 × 320 nm PRINT particles in four subcutaneous flank tumor models (SKOV3 human ovarian, 344SQ murine nonsmall cell lung, A549 human nonsmall cell lung, and A431 human epidermoid cancer). Each tumor model revealed specific particle accumulation trends with evident particle size dependence.

Dual Character Concepts in Social Cognition: Commitments and the Normative Dimension of Conceptual Representation.

The concepts expressed by social role terms such as artist and scientist are unique in that they seem to allow two independent criteria for categorization, one of which is inherently normative (Knobe, Prasada, & Newman, 2013). This study presents and tests an account of the content and structure of the normative dimension of these "dual character concepts." Experiment 1 suggests that the normative dimension of a social role concept represents the commitment to fulfill the idealized basic function associated with the role.

Making It Safe to Grow Old: A Financial Simulation Model for Launching MediCaring Communities for Frail Elderly Medicare Beneficiaries.

Policy Points: At age 65, the average man and woman can respectively expect 1.5 years and 2.5 years of requiring daily help with "activities of daily living.

Targeted PRINT Hydrogels: The Role of Nanoparticle Size and Ligand Density on Cell Association, Biodistribution, and Tumor Accumulation.

In this Letter, we varied targeting ligand density of an EGFR binding affibody on the surface of two different hydrogel PRINT nanoparticles (80 nm × 320 and 55 nm × 60 nm) and monitored effects on target-cell association, off-target phagocytic uptake, biodistribution, and tumor accumulation. Interestingly, variations in ligand density only significantly altered in vitro internalization rates for the 80 nm × 320 nm particle. However, in vivo, both particle sizes experienced significant changes in biodistribution and pharmacokinetics as a function of ligand density.

Calibration-quality cancer nanotherapeutics.

Nanoparticle properties such as size, shape, deformability, and surface chemistry all play a role in nanomedicine drug delivery in cancer. While many studies address the behavior of particle systems in a biological setting, revealing how these properties work together presents unique challenges on the nanoscale. "Calibration-quality" control over such properties is needed to draw adequate conclusions that are independent of parameter variability.

Evaluation of drug loading, pharmacokinetic behavior, and toxicity of a cisplatin-containing hydrogel nanoparticle.

Cisplatin is a cytotoxic drug used as a first-line therapy for a wide variety of cancers. However, significant renal and neurological toxicities limit its clinical use. It has been documented that drug toxicities can be mitigated through nanoparticle formulation, while simultaneously increasing tumor accumulation through the enhanced permeation and retention effect.

Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model.

Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of inherent cytotoxic or immunostimulatory properties. Therefore, determining baseline immune responses to nanomaterials is of utmost importance when designing human therapeutics. We characterized the response of human immune cells to hydrogel NPs fabricated using Particle Replication in Non-wetting Templates (PRINT) technology.

The good, the bad, and the timely: how temporal order and moral judgment influence causal selection.

Causal selection is the cognitive process through which one or more elements in a complex causal structure are singled out as actual causes of a certain effect. In this paper, we report on an experiment in which we investigated the role of moral and temporal factors in causal selection. Our results are as follows.

PEGylated PRINT nanoparticles: the impact of PEG density on protein binding, macrophage association, biodistribution, and pharmacokinetics.

In this account, we varied PEGylation density on the surface of hydrogel PRINT nanoparticles and systematically observed the effects on protein adsorption, macrophage uptake, and circulation time. Interestingly, the density of PEGylation necessary to promote a long-circulating particle was dramatically less than what has been previously reported. Overall, our methodology provides a rapid screening technique to predict particle behavior in vivo and our results deliver further insight to what PEG density is necessary to facilitate long-circulation.

Solid core column technology applied to HPLC-FD of paralytic shellfish toxins.

Pre-column oxidation liquid chromatography with fluorescence detection is a chemical method for analyzing paralytic shellfish toxins. In order to improve the sample throughput and efficiency of AOAC Method 2005.06, solid core particle column technology was evaluated.