Outcome of a questionnaire within European pharmaceutical aerosol group (EPAG) companies concerning the implementation of the abbreviated impactor measurement (AIM) concept for the assessment of orally inhaled product (OIP) aerosol aerodynamic particle size properties

The AIM Concept as an augmentation of full resolution cascade impactor (CI) measurements of the aerodynamic properties of aerosols emitted by OIPs has been in existence for about ten years. A previous EPAG-based survey undertaken five years ago indicated significant interest in the approach, particularly for the screening of candidate products in early stage product development. We report the outcome of a further questionnaire with the goals of establishing: (a) the types of AIM-based equipment currently in use; and (b) insight into perceived hurdles towards full implementation within the product lifecycle. Responses were received in October 2016 from 17 out of 22 organizations from people involved directly with the in vitro testing of pressurized metered dose inhaler (pMDI) and dry powder inhaler (DPI) products. The survey has shown that the AIM concept has sufficient popularity within the EPAG respondent organizations to be considered a viable augmentation to existing full resolution CI methodology. The main conclusions are: (1) The Fast Screening Andersen (FSA), reduced Next Generation Impactor (rNGI) and Fast Screening Impactor (FSI) are all used as AIM-based impactor configurations for both dry powder inhaler (DPI) and pressurized metered dose inhaler (pMDI) applications; (2) AIM-based methods are used almost entirely for the early development phase of the OIP life cycle; (3) Organizations in general do not have confidence to use the AIM concept more widely in the product life cycle whilst no compendial/regulatory guidance is available to provide standard procedures and precautions/regulatory acceptance respectively

A European Pharmaceutical Aerosol Group (EPAG)-led cross-industry assessment of inlet flow rate profiles of compendial DPI test systems: Part 1 – experimental data

We report outcomes from an EPAG-led cross-industry study, characterizing flow rate/elapsed-time profiles of equipment used for testing dry powder inhalers (DPIs). A thermal mass flow sensor was used by nine organizations in a round-robin approach to record inlet flow rate-time profiles of individual participant compendial test systems (TS) including either sample collection tubes (SCT) or a cascade impactor (either the Andersen 8-stage non-viable impactor, ACI, or the Next Generation Impactor, NGI) equipped with USP/PhEur induction port and pre-separator. An inlet orifice generated a 4-kPa pressure drop at each of the target flow rates (30, 60 and 90 L/min), simulating a pressure drop typical for high-, medium- and low-resistance DPIs respectively. Rise times to 90% of these target flow rates (t90) were longest with largest internal dead volume and followed the order NGI>ACI >SCT>TS. When the surrogate DPI (4-kPa orifice) was absent, t90 values generally lengthened with increasing target flow rate. In contrast, the opposite behaviour was observed when the surrogate DPI was present. A flow acceleration parameter was also calculated, expressed as the slope between the 20% and 80% flow rates of each final steady flow value (slopet20/t80). Greater flow acceleration occurred at higher final flow rates, irrespective of apparatus, but the presence of the surrogate DPI was associated with slower flow acceleration. These flow rate-rise time profiles will be useful for those involved in evaluating equipment for characterizing both existing and new DPIs

Two-photon final states in peripheral heavy ion collisions

We discuss processes leading to two photon final states in peripheral heavy ion collisions at RHIC. Due to the large photon luminosity we show that the continuum subprocess $\gamma \gamma \to \gamma \gamma$ can be observed with a large number of events. We study this reaction when it is intermediated by a resonance made of quarks or gluons and discuss its interplay with the continuum process, verifying that in several cases the resonant process ovewhelms the continuum one. It is also investigated the possibility of observing a scalar resonance (the $\sigma$ meson) in this process. Assuming for the $\sigma$ the mass and total decay width values recently reported by the E791 Collaboration we show that RHIC may detect this particle in its two photon decay mode if its partial photonic decay width is of the order of the ones discussed in the literature.Comment: 10 pages, 8 figure

Reactions to messages about smoking, vaping and COVID-19: Two national experiments

Introduction The pace and scale of the COVID-19 pandemic, coupled with ongoing efforts by health agencies to communicate harms, have created a pressing need for data to inform messaging about smoking, vaping, and COVID-19. We examined reactions to COVID-19 and traditional health harms messages discouraging smoking and vaping. Methods Participants were a national convenience sample of 810 US adults recruited online in May 2020. All participated in a smoking message experiment and a vaping message experiment, presented in a random order. In each experiment, participants viewed one message formatted as a Twitter post. The experiments adopted a 3 (traditional health harms of smoking or vaping: Three harms, one harm, absent) × 2 (COVID-19 harms: one harm, absent) between-subjects design. Outcomes included perceived message effectiveness (primary) and constructs from the Tobacco Warnings Model (secondary: Attention, negative affect, cognitive elaboration, social interactions). Results Smoking messages with traditional or COVID-19 harms elicited higher perceived effectiveness for discouraging smoking than control messages without these harms (all p <0.001). However, including both traditional and COVID-19 harms in smoking messages had no benefit beyond including either alone. Smoking messages affected Tobacco Warnings Model constructs and did not elicit more reactance than control messages. Smoking messages also elicited higher perceived effectiveness for discouraging vaping. Including traditional harms in messages about vaping elicited higher perceived effectiveness for discouraging vaping (p <0.05), but including COVID-19 harms did not. Conclusions Messages linking smoking with COVID-19 may hold promise for discouraging smoking and may have the added benefit of also discouraging vaping

A framework for the local information dynamics of distributed computation in complex systems

The nature of distributed computation has often been described in terms of the component operations of universal computation: information storage, transfer and modification. We review the first complete framework that quantifies each of these individual information dynamics on a local scale within a system, and describes the manner in which they interact to create non-trivial computation where "the whole is greater than the sum of the parts". We describe the application of the framework to cellular automata, a simple yet powerful model of distributed computation. This is an important application, because the framework is the first to provide quantitative evidence for several important conjectures about distributed computation in cellular automata: that blinkers embody information storage, particles are information transfer agents, and particle collisions are information modification events. The framework is also shown to contrast the computations conducted by several well-known cellular automata, highlighting the importance of information coherence in complex computation. The results reviewed here provide important quantitative insights into the fundamental nature of distributed computation and the dynamics of complex systems, as well as impetus for the framework to be applied to the analysis and design of other systems.Comment: 44 pages, 8 figure

The CLIMPACTS synthesis report: An assessment of the effects of climate change and variation in New Zealand using the CLIMPACTS system

In the late 1980s, New Zealand undertook the first national assessment of climate change and its possible impacts on the country.The landmark report, reflecting the judgement of scores of national experts, called for greater efforts in building the national research capacity in order to better quantify the range of impacts that could occur in New Zealand from climate change and variability. In response, the collaborative CLIMPACTS Programme was established to provide this capacity. Ten years on from the first national assessment, the present synthesis offers some results from, as well as a demonstration of, the capacity developed by the CLIMPACTS Programme. The purpose of the present document is to provide a summary report from the CLIMPACTS Programme on climate change and its effects on New Zealand.The chapters and their contents are not comprehensive. Rather, they are focused on a specific set of questions, which conform to the particular expertise of the CLIMPACTS Programme members and which employ a limited set of the wide range of tools available within the CLIMPACTS Model. Other important areas such as forests, indigenous ecosystems and pests and diseases are not yet covered

Can forest management based on natural disturbances maintain ecological resilience?

Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10−8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs49654