Nicotine vaping product use, harm perception and policy support among pharmacy customers in Brisbane, Australia

Despite regulatory barriers for accessing nicotine liquid, use of nicotine vaping products (NVPs) has increased rapidly in Australia. Legal use of NVPs to aid smoking cessation requires a prescription, and pharmacies report receiving enquiries about the use of and access to NVPs. In this study, we assessed vaping product use, harm perception and policy support among community pharmacy customers.A cross-sectional survey was conducted among customers (n = 470) from a large community pharmacy chain in Brisbane, Australia. Multivariable logistic regression was used to examine perception of NVPs as less harmful than combustible cigarettes and regulatory recommendations in relation to demographics, smoking status and NVP use.Almost one-third of the sample (31%) had either tried NVPs in the past (16%) or were current vapers (15%), the majority of them being current smokers (67%) who are trying to quit (31%) or substitute smoking (41%). Vapers primarily depended on family/friends as a source of information (76%). Current smokers and vapers were more likely to perceive NVPs as less harmful than cigarettes than non-smokers and non-vapers. Perceiving NVPs as safer than cigarettes was correlated with a recommendation to regulate as a tobacco product.There was widespread misperception about relative risk of nicotine-containing products, with 37% of respondents perceiving nicotine-containing NVPs to be as harmful as combustible cigarettes. Community pharmacies represent an ideal setting for educating smokers about smoking and vaping. Thus, pharmacy staff needs educational support to ensure that they are equipped to provide current evidence-based information to customers

Framing and scientific uncertainty in nicotine vaping product regulation: An examination of competing narratives among health and medical organisations in the UK, Australia and New Zealand

Aims To compare the policy positions of health and medical organisations across Australia, New Zealand, and the UK as they relate to sale and supply of nicotine vaping products (NVPs) and evaluate factors that have informed the differences in policy recommendations among these countries. Methods We used mixed methods to analyse data from position or policy statements published by health and medical organisations regarding NVPs (n = 30) and consultation documents submitted to government committees regarding policy options for the regulation of NVPs (n = 26). Quality assessment of included documents was conducted using the six-item Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Text and Opinion Papers, and findings were presented narratively. Qualitative data were coded using NVivo 12 software and analysed using thematic analysis. Results An overwhelming majority of health bodies, charities and government agencies in the UK and New Zealand portrayed NVPs as a life-saving harm reduction tool. In contrast, concerns about addicting non-smoking youth to nicotine, a perceived lack of clear and convincing evidence of safety and efficacy and the potential to undermine tobacco control progress continues to define attitudes and recommendations towards NVPs among Australian health and medical organisations. Although the profoundly divided views among stakeholders seem to arise from empirical uncertainties and disagreements over the level and credibility of evidence, the source of most of these disagreements can be traced back to the fundamental and irreconcilable differences in the framing of the NVP debate, and varied tolerability of risk trade-offs associated with NVPs. Conclusion Progress in resolving the controversy surrounding NVP policy requires stakeholders to be frame-reflective and engage in a meaningful dialogue of risk trade-offs, as well as both intended and unintended consequences of proposed policies

Discrete Effects in Stellar Feedback: Individual Supernovae, Hypernovae, and IMF Sampling in Dwarf Galaxies

Using high-resolution simulations from the FIRE-2 (Feedback In Realistic Environments) project, we study the effects of discreteness in stellar feedback processes on the evolution of galaxies and the properties of the interstellar medium (ISM). We specifically consider the discretization of supernovae (SNe), including hypernovae (HNe), and sampling the initial mass function (IMF). We study these processes in cosmological simulations of dwarf galaxies with $z=0$ stellar masses $M_{\ast}\sim 10^{4}-3\times10^{6}\,M_\odot$ (halo masses $\sim 10^{9}-10^{10}\,M_\odot$). We show that the discrete nature of individual SNe (as opposed to a model in which their energy/momentum deposition is continuous over time, similar to stellar winds) is crucial in generating a reasonable ISM structure and galactic winds and in regulating dwarf stellar masses. However, once SNe are discretized, accounting for the effects of IMF sampling on continuous mechanisms such as radiative feedback and stellar mass-loss (as opposed to adopting IMF-averaged rates) has weak effects on galaxy-scale properties. We also consider the effects of rare HNe events with energies $\sim 10^{53}\,{\rm erg}$. The effects of HNe are similar to the effects of clustered explosions of SNe -- which are already captured in our default simulation setup -- and do not quench star formation (provided that the HNe do not dominate the total SNe energy budget), which suggests that HNe yield products should be observable in ultra-faint dwarfs today.Comment: 9 pages, 4 figure

Design, construction and control of a unidirectional tele-operated seismic simulator for testing small scale structural models

Este artículo presenta el diseño, construcción y control de un simulador sísmico uniaxial para modelos estructurales de pequeña escala. Inicialmente, el documento muestra el diseño de cada parte del simulador hasta llegar a la construcción de todo el prototipo. Luego, se halla un modelo matemático del simulador utilizando un procedimiento de identificación en el lazo de velocidad que se valida mediante respuesta en frecuencia. A partir del modelo identificado se diseñan los controladores de los lazos de velocidad y posición, que proveen al sistema el desempeño requerido. Finalmente, se presentan varias pruebas para la validación del simulador sísmico y se describe la interfaz de control remota desarrollada en Java®, que permite al usuario definir las señales de excitación, visualizar los registros obtenidos de la prueba y observar el video en línea desde Internet

A phenome-wide comparative analysis of genetic discordance between obesity and type 2 diabetes

Obesity and type 2 diabetes are causally related, yet there is considerable heterogeneity in the consequences of both conditions and the mechanisms of action are poorly defined. Here we show a genetic-driven approach defining two obesity profiles that convey highly concordant and discordant diabetogenic effects. We annotate and then compare association signals for these profiles across clinical and molecular phenotypic layers. Key differences are identified in a wide range of traits, including cardiovascular mortality, fat distribution, liver metabolism, blood pressure, specific lipid fractions and blood levels of proteins involved in extracellular matrix remodelling. We find marginal differences in abundance of Bacteroidetes and Firmicutes bacteria in the gut. Instrumental analyses reveal prominent causal roles for waist-to-hip ratio, blood pressure and cholesterol content of high-density lipoprotein particles in the development of diabetes in obesity. We prioritize 17 genes from the discordant signature that convey protection against type 2 diabetes in obesity, which may represent logical targets for precision medicine approaches.</p

Monomeric C-Reactive Protein Aggravates Secondary Degeneration after Intracerebral Haemorrhagic Stroke and May Function as a Sensor for Systemic Inflammation.

BACKGROUND:We previously identified increased tissue localization of monomeric C-reactive protein (mCRP) in the infarcted cortical brain tissue of patients following ischaemic stroke. Here, we investigated the relationship of mCRP expression in haemorrhagic stroke, and additionally examined the capacity of mCRP to travel to or appear at other locations within the brain that might account for later chronic neuroinflammatory or neurodegenerative effects. METHODS:Immunohistochemistry was performed on Formalin-fixed, paraffin-embedded archived brain tissue blocks obtained at autopsy from stroke patients and age-matched controls. We modelled mCRP migration into the brain after haemorrhagic stroke by infusing mCRP (3.5 µg) into the hippocampus of mice and localized mCRP with histological and immunohistochemistry methods. RESULTS:On human tissue in the early stages of haemorrhage, there was no staining of mCRP. However, with increasing post-stroke survival time, mCRP immunostaining was associated with some parenchymal brain cells, some stroke-affected neurons in the surrounding areas and the lumen of large blood vessels as well as brain capillaries. Further from the peri-haematoma region, however, mCRP was detected in the lumen of micro-vessels expressing aquaporin 4 (AQP4). In the hypothalamus, we detected clusters of neurons loaded with mCRP along with scattered lipofuscin-like deposits. In the peri-haematoma region of patients, mCRP was abundantly seen adjacent to AQP4 immunoreactivity. When we stereotactically injected mCRP into the hippocampus of mice, we also observed strong expression in distant neurones of the hypothalamus as well as cortical capillaries. CONCLUSIONS:mCRP is abundantly expressed in the brain after haemorrhagic stroke, directly impacting the pathophysiological development of the haematoma. In addition, it may have indirect effects, where the microcirculatory system appears to be able to carry it throughout the cortex as far as the hypothalamus, allowing for long-distance effects and damage through its capacity to induce inflammation and degenerate neuronal perivascular compartments

4D Multimodal Nanomedicines Made of Nonequilibrium Au-Fe Alloy Nanoparticles

Several examples of nanosized therapeutic and imaging agents have been proposed to date, yet for most of them there is a low chance of clinical translation due to long-term in vivo retention and toxicity risks. The realization of nanoagents that can be removed from the body after use remains thus a great challenge. Here, we demonstrate that nonequilibrium gold–iron alloys behave as shape-morphing nanocrystals with the properties of self-degradable multifunctional nanomedicines. DFT calculations combined with mixing enthalpy-weighted alloying simulations predict that Au–Fe solid solutions can exhibit self-degradation in an aqueous environment if the Fe content exceeds a threshold that depends upon element topology in the nanocrystals. Exploiting a laser-assisted synthesis route, we experimentally confirm that nonequilibrium Au–Fe nanoalloys have a 4D behavior, that is, the ability to change shape, size, and structure over time, becoming ultrasmall Au-rich nanocrystals. In vivo tests show the potential of these transformable Au–Fe nanoalloys as efficient multimodal contrast agents for magnetic resonance imaging and computed X-ray absorption tomography and further demonstrate their self-degradation over time, with a significant reduction of long-term accumulation in the body, when compared to benchmark gold or iron oxide contrast agents. Hence, Au–Fe alloy nanoparticles exhibiting 4D behavior can respond to the need for safe and degradable inorganic multifunctional nanomedicines required in clinical translation.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasInstituto de Física La Plat

Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle

α-Dystrobrevin is a component of the dystrophin-glycoprotein complex (DGC) and is thought to have both structural and signaling roles in skeletal muscle. Mice deficient for α-dystrobrevin (adbn−/−) exhibit extensive myofiber degeneration and neuromuscular junction abnormalities. However, the biochemical stability of the DGC and the functional performance of adbn−/− muscle have not been characterized. Here we show that the biochemical association between dystrophin and β-dystroglycan is compromised in adbn−/− skeletal muscle, suggesting that α-dystrobrevin plays a structural role in stabilizing the DGC. However, despite muscle cell death and DGC destabilization, costamere organization and physiological performance is normal in adbn−/− skeletal muscle. Our results demonstrate that myofiber degeneration alone does not cause functional deficits and suggests that more complex pathological factors contribute to the development of muscle weakness in muscular dystrophy

A Federated Database for Obesity Research:An IMI-SOPHIA Study

Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders.</p

A Federated Database for Obesity Research:An IMI-SOPHIA Study

Obesity is considered by many as a lifestyle choice rather than a chronic progressive disease. The Innovative Medicines Initiative (IMI) SOPHIA (Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy) project is part of a momentum shift aiming to provide better tools for the stratification of people with obesity according to disease risk and treatment response. One of the challenges to achieving these goals is that many clinical cohorts are siloed, limiting the potential of combined data for biomarker discovery. In SOPHIA, we have addressed this challenge by setting up a federated database building on open-source DataSHIELD technology. The database currently federates 16 cohorts that are accessible via a central gateway. The database is multi-modal, including research studies, clinical trials, and routine health data, and is accessed using the R statistical programming environment where statistical and machine learning analyses can be performed at a distance without any disclosure of patient-level data. We demonstrate the use of the database by providing a proof-of-concept analysis, performing a federated linear model of BMI and systolic blood pressure, pooling all data from 16 studies virtually without any analyst seeing individual patient-level data. This analysis provided similar point estimates compared to a meta-analysis of the 16 individual studies. Our approach provides a benchmark for reproducible, safe federated analyses across multiple study types provided by multiple stakeholders