The effect of branded versus standardized e-cigarette packaging and device designs: an experimental study of youth interest in vaping products.

OBJECTIVES: Standardized ('plain') packaging is effective in reducing the appeal of cigarettes among young people. This study examined the impact of plain packaging and brand imagery on interest in trying e-cigarettes among youth. STUDY DESIGN: Experimental design. METHODS: Two online experiments were conducted in February 2020 as part of the ITC Youth Tobacco & Vaping Survey, conducted with 13,624 16- to 19-year-olds in Canada, England, and the USA. In the between-group Experiment 1, participants were randomized to view a set of 3 e-cigarette brands, in either their original external packaging ('branded' condition) or standardized olive-green packaging ('standardized' condition), and asked to select the product they would be most interested in trying. The within-group Experiment 2 examined brand imagery directly on devices, including potential differences in appeal among subgroups. Each participant viewed 4 pod-style e-cigarette devices: one 'plain' and 3 in colourful 'skins'. Logistic regression models were conducted to test the effect of condition, adjusting for demographics, smoking and vaping status. RESULTS: In Experiment 1, participants in the 'standardized' packaging condition were significantly more likely to indicate 'I have no interest in trying any of these products' (72.3%) than those in the 'branded' condition (66.9%, AOR 1.45, 95% CI 1.33-1.59). Experiment 2 results indicated differences in e-cigarette appeal by sex in the selection of male- and female-oriented designs, and by cannabis use for a Rastafarian-themed design. CONCLUSIONS: Brand imagery on e-cigarettes can target products to specific subgroups. Removal of imagery, in the form of standardized packaging, has the potential to reduce interest in trying e-cigarettes among young people.

"You don't put it down to arthritis": A qualitative study of the first symptoms recalled by individuals with knee osteoarthritis.

Objective: As part of the first phase of the OARSI Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) initiative, we explored the first symptoms and experiences recalled by individuals with knee osteoarthritis (OA). Design: This qualitative study, informed by qualitative description, was a secondary analysis of focus groups (n â€‹= â€‹17 groups) and one-on-one interviews (n â€‹= â€‹3) conducted in 91 individuals living with knee OA as part of an international study to better understand the OA pain experience. In each focus group or interview, participants were asked to describe their first symptoms of knee OA. We inductively coded these transcripts and conducted thematic analysis. Results: Mean age of participants was 70 years (range 47-92) and 68 â€‹% were female. We developed four overarching themes: Insidious and Episodic Onset, Diverse Early Symptoms, Must be Something Else, and Adjustments. Participants described the gradual and intermittent way in which symptoms of knee OA developed over many years; many could not identify a specific starting point. Participants described diverse initial knee symptoms, including activity-exacerbated joint pain, stiffness and crepitus. Most participants dismissed early symptoms or rationalized their presence, employing various strategies to enable continued participation in recreational and daily activities. Few sought medical attention until physical functioning was demonstrably impacted. Conclusions: The earliest symptoms of knee OA are frequently insidious in onset, episodic and present long before individuals present to health professionals. These results highlight challenges to identifying people with knee OA early and support the development of specific classification criteria for EsSKOA to capture individuals at an early stage.

Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

Application of Silica-Aerogel-Fibre-Based Thermal Renders for Retrofits in Building Walls: A Comparative Assessment with Benchmark Solutions.

The current climate change context raises the demand for reducing energy and environmental impacts while keeping an economic balance and building users' comfort. Thermal insulation solutions are potential allies in ensuring the adequacy of existing buildings for challenging sustainability requirements. In this scenario, silica-aerogel-fibre-based thermal renders are innovative solutions for which integrated approaches still lack information, and they should be compared with benchmark multilayer solutions, such as those based on expanded polystyrene (EPS), extruded polystyrene (XPS), mineral wool (MW), and insulated corkboard (ICB), to evidence their prospective economic, environmental, and energy benefits. This paper quantifies the optimum insulation thicknesses, life cycle savings, payback periods, and environmental impacts of innovative thermal renders compared to conventional thermal insulation materials when applied as a retrofit in existing facade walls. The results show that cost-optimised thermal renders with sisal fibres led to the best overall performance. Higher heating needs led to higher optimum render thicknesses and life cycle savings. With a 0.02 m thickness, aerogel-fibre-based thermal renders outperformed other materials in terms of heating-degree days (HDD) from 1000 °C·day onwards; they can save approximately EUR 60∙m-2, 1000 MJ∙m-2, and 100 kg CO2 eq∙m-2 while presenting a U-value 13% lower throughout their 30-year lifetime when compared with the second-best multilayer solution with XPS.

Physical properties of a generalized model of multilayer adsorption of dimers.

We investigate the transport properties of a complex porous structure with branched fractal architectures formed due to the gradual deposition of dimers in a model of multilayer adsorption. We thoroughly study the interplay between the orientational anisotropy parameter p_{0} of deposited dimers and the formation of porous structures, as well as its impact on the conductivity of the system, through extensive numerical simulations. By systematically varying the value of p_{0}, several critical and off-critical scaling relations characterizing the behavior of the system are examined. The results demonstrate that the degree of orientational anisotropy of dimers plays a significant role in determining the structural and physical characteristics of the system. We find that the Einstein relation relating to the size scaling of the electrical conductance holds true only in the limiting case of p_{0}→1. Monitoring the fractal dimension of the interface of the multilayer formation for various p_{0} values, we reveal that in a wide range of p_{0}>0.2 interface shows the characteristic of a self-avoiding random walk, compared to the limiting case of p_{0}→0 where it is characterized by the fractal dimension of the backbone of ordinary percolation cluster at criticality. Our results thus can provide useful information about the fundamental mechanisms underlying the formation and behavior of wide varieties of amorphous and disordered systems that are of paramount importance both in science and technology as well as in environmental studies.

On the estimation of the effect of weight change on a health outcome using observational data, by utilising the target trial emulation framework.

BACKGROUND/OBJECTIVES: When studying the effect of weight change between two time points on a health outcome using observational data, two main problems arise initially (i) 'when is time zero?' and (ii) 'which confounders should we account for?' From the baseline date or the 1st follow-up (when the weight change can be measured)? Different methods have been previously used in the literature that carry different sources of bias and hence produce different results. METHODS: We utilised the target trial emulation framework and considered weight change as a hypothetical intervention. First, we used a simplified example from a hypothetical randomised trial where no modelling is required. Then we simulated data from an observational study where modelling is needed. We demonstrate the problems of each of these methods and suggest a strategy. INTERVENTIONS: weight loss/gain vs maintenance. RESULTS: The recommended method defines time-zero at enrolment, but adjustment for confounders (or exclusion of individuals based on levels of confounders) should be performed both at enrolment and the 1st follow-up. CONCLUSIONS: The implementation of our suggested method [adjusting for (or excluding based on) confounders measured both at baseline and the 1st follow-up] can help researchers attenuate bias by avoiding some common pitfalls. Other methods that have been widely used in the past to estimate the effect of weight change on a health outcome are more biased. However, two issues remain (i) the exposure is not well-defined as there are different ways of changing weight (however we tried to reduce this problem by excluding individuals who develop a chronic disease); and (ii) immortal time bias, which may be small if the time to first follow up is short.

Exposure to Pfaffia glomerata causes oxidative stress and triggers hepatic changes.

Medicinal plant species are genetically engineered to obtain higher production of biomass and specific secondary metabolites, which can be used in the pharmaceutical industry. The aim of the present study was to evaluate the effect of Pfaffia glomerata (Spreng.) Pedersen tetraploid hydroalcoholic extract on the liver of adult Swiss mice. The extract was prepared from the plant roots and given to the animals by gavage, for 42 days. The experimental groups were treated with water (control), Pfaffia glomerata tetraploid hydroalcoholic extract (100, 200 and 400 mg/kg) and Pfaffia glomerata tetraploid hydroalcoholic extract discontinuously (200 mg/kg). The last group received the extract every 3 days, for 42 days. The oxidative status, mineral dynamics, and cell viability were analysed. The liver weight and the number of viable hepatocytes were reduced, despite the increased cell's number. Increased levels of malondialdehyde and nitric oxide, and changes in iron, copper, zinc, potassium, manganese and sodium levels were observed. aspartate aminotransferase levels were increased while alanine aminotransferase levels were decreased due to BGEt intake. Our results showed that BGEt induced alterations of oxidative stress biomarkers leading to liver injury, which was associated with a reduction in the number of hepatocytes.

Alkylphosphonium carboxylate ionic liquids with tuned microscopic structures and properties.

Eleven pure alkylphosphonium carboxylate ionic liquids (ILs) were synthesised following a reliable and accessible route. Tetrabutylphosphonium and tetradecyltrihexylphosphonium cations were associated to a variety of [R-COO]- anions with R varying from shorter to longer linear alkyl chains; smaller to bulkier branched alkyl chains; cyclic saturated aliphatic and aromatic moieties; and one heterocyclic aromatic ring containing nitrogen. A combined experimental and molecular simulation study allowed the full characterization of the physico-chemical properties, the structure and the thermal stability of the synthesized ILs. Although slightly more viscous than their imidazolium counterparts, the viscosities of the prepared salts decrease dramatically with temperature and are comparable to other ILs above 50 °C, a manageable temperature as they are thermally stable up to temperatures above 250 °C, even under an oxidizing atmosphere. The microscopic structure of the phophonium ILs is rich and has been studied both experimentally using SAXS and by molecular dynamics simulation using state of the art polarizable force fields whose parameters were determined when necessary. Unique and surprising anion-anion correlations were found for the tetrazolate-based IL allowing to explain some of the unique physical-chemical properties of this phosphonium salt.

Infiltration OF 5Y-PSZ with thermally compatible glass: Strength, microstructure and failure mode analyses.

This study set out to develop a thermally compatible glass to be infiltrated into zirconia partially stabilized by yttrium oxide (5Y-PSZ), to characterize it, and to evaluate its structural reliability and mechanical behavior. 5Y-PSZ zirconia discs (N = 90), dimensions 1.5 mm × 15 mm were produced, polished with #600 alumina oxide and #1200 silicon carbide sandpaper in a polisher. Three groups of 5Y-PSZ discs were assigned (n = 30): Zctrl: as sintered zirconia, Zinf-comp: glass-infiltrated zirconia on the occlusal surface, and sintered, and Zinf-tens: glass-infiltrated zirconia on the cementing surface and sintered; for biaxial flexural strength testing (ISO 6872:2015). A gel was synthesized via the sol-gel method and applied to the ceramic surface. Mechanical assay data (MPa) were evaluated via Weibull analysis (α = 5%) and specimens via X-Ray Diffractometry (XRD), Scanning Electron Microscopy (SEM), and fractographic analysis. The Zinf-tens group showed a characteristic strength of 824 MPa and m = 9.9; Zinf-comp 613 MPa and m = 10.2; Zctrl 534 MPa and m = 8; all groups differed statistically (σ0). However, they were similar in structural homogeneity (m). XRD showed 20-50 µm of infiltration, which means dissolution of part of the yttrium and reduction in the size of the cubic grains. In addition, the Zinf-tens group presented a failure origin from inside the material. The developed glass infiltrated into zirconia partially stabilized by yttrium oxide, increasing its characteristic strength and structural homogeneity by reducing surface defects and changing the failure mode.

Over-blending effect of lubricants on capsules manufacturing: a simple and fast wettability technique to predict batch dissolution performance.

Mixing/blending is a crucial operation in the manufacturing of solid drug products in the pharmaceutical industry. Although usually described and controlled in specific steps, blending is also inherent to other operations such as the transference of materials and equipment feeding systems. This study aimed to investigate a simple and fast wettability testing procedure capable to foresee the potential over-blending effects of lubricants occurring during the manufacturing of solid dosage forms. An industrial batch blend was submitted to two mixing mechanisms studies (diffusion and shear) during increasing time periods, and the developed wettability testing procedure was applied to assess their impact on blend water uptake. Capsules filled with these blends were tested for dissolution and disintegration. The method was applied to capsules with known dissolution results manufactured at an industrial scale. Results demonstrated that processes inducing shear stress led to less permeable blends with consequent retardation on capsules dissolution of at least 35% in the tested timepoints and obtained study metrics above 500 s. Moreover, disintegration testing was not able to detect non-compliant dissolutions, while the proposed wettability testing procedure proved to be able to identify performance failures. Wettability results correlate the effect of mixing mechanisms to capsules dissolution performance, evidencing that this technique can be applied in the pharmaceutical industry to evaluate possible over-blending effects.

The impact of having a carer on adult health and social care utilisation across five settings of care: A matched cohort study.

INTRODUCTION: An estimated 6.8 million people are (informal) carers in the UK. The economic value of annual carer contributions is an estimated .·132bn. Reliance on carers appears to be increasing. There is mixed evidence on whether carers are substitutes for formal care. This study investigated the association between having a carer and service use patterns across five care settings when compared to a matched cohort without a carer. MATERIALS AND METHODS: A matched case-control group analysis using person-level data in Barking and Dagenham (B&D), a London borough in the U.K., to assess the impact of having a carer in terms of the differences in cost-weighted utilisation relative to a matched control group. RESULTS: In 2016/17, for adult residents of B&D, having a carer (n = 1,295) was associated with 27% increased cost-weighted utilisation (mean difference of £2,662, CI £1,595, £3,729, p<0.001) compared to a matched cohort without a carer. 39% of the cost difference was social care. CONCLUSIONS: Findings suggest additional service use induced by carers may dominate any substitution effect. Having a carer may be a key element in enabling access to services. As such, there may be wider inequalities in service access for people without a carer. For an ageing society with projections suggesting there will be more people without carers in the future, these inequalities need to be addressed.

Design of an artificial phage-display library based on a new scaffold improved for average stability of the randomized proteins.

Scaffold-based protein libraries are designed to be both diverse and rich in functional/folded proteins. However, introducing an extended diversity while preserving stability of the initial scaffold remains a challenge. Here we developed an original approach to select the ensemble of folded proteins from an initial library. The thermostable CheY protein from Thermotoga maritima was chosen as scaffold. Four loops of CheY were diversified to create a new binding surface. The subset of the library giving rise to folded proteins was first selected using a natural protein partner of the template scaffold. Then, a gene shuffling approach based on a single restriction enzyme was used to recombine DNA sequences encoding these filtrated variants. Taken together, the filtration strategy and the shuffling of the filtrated sequences were shown to enrich the library in folded and stable sequences while maintaining a large diversity in the final library (Lib-Cheytins 2.1). Binders of the Oplophorus luciferase Kaz domain were then selected by phage display from the final library, showing affinities in the µM range. One of the best variants induced a loss of 92% of luminescent activity, suggesting that this Cheytin preferentially binds to the Kaz active site.

Decline of tuberculosis notification rate in different populations and regions in Portugal, 2010-2017.

BACKGROUND: Tuberculosis (TB) incidence declined in Portugal in recent decades, but trends differ between regions and population subgroups. We investigated these differences to inform prevention and control programmes. METHODS: We extracted TB notifications from the Portuguese National TB Surveillance System (SVIG-TB) in 2010-2017, disaggregated by region, age group, nationality and HIV status. We calculated notification rates using denominators from the Portuguese National Institute of Statistics and the Joint United Nations Programme on HIV/AIDS and performed stratified time series analysis. We estimated interannual decline percentages and 95% confidence intervals (CI) using Poisson and binomial negative regression models. RESULTS: The overall TB notification rate decreased from 25.7 to 17.5/100,000 population from 2010 to 2017 (5.2%/year) in Portugal. Interannual decline did not differ significantly between regions, but it was smaller amongst non-Portuguese nationals (-1.57% [CI: -4.79%, 1.75%] vs -5.85% [CI: -6.98%, -4.70%] in Portuguese nationals); children under five years of age (+1.77% [CI: -4.61%, 8.58%] vs -5.38% [CI: -6.33%, -4.42%] in other age groups); and HIV-negative people (-6.47% [CI: -9.10%, -3.77%] vs -11.29% [CI; -17.51%, -4.60%] in HIV-positive). CONCLUSIONS: The decline in TB notification rates in Portugal during the study period has been steady. However, the decline amongst non-Portuguese nationals, children under five years of age and non-infected-HIV patients was lower. No significant differences were observed between regions. Changes in TB epidemiology in specific risk groups and geographical areas should be closely monitored to achieve the objectives of the End TB Strategy. We recommend intensifying screening of TB in the subpopulations identified.

King George III of England and Queen Maria I of Portugal: bipolar disorder and prince regents as common features of their reigns.

ABSTRACT: Humanity is sporadically subjected to leaders with deviant behavior, ego problems, or psychiatric disorders, potentially leading to social instability. Bipolar disorder is not common in all populations, but, coincidentally, studies suggest that it affected two sovereigns that were contemporaries, King George III of England, who died 201 years ago, and Queen Maria I of Portugal, who died 205 years ago. They lived during a time when Europe was in turmoil with the French Revolution and Napoleonic Wars, which also coincided with the rise of psychiatry. Both monarchs were forced to have prince regents rule in their place, due to their emotional decline, and they shared the same medical consultant, Francis Willis.

King George III of England and Queen Maria I of Portugal: bipolar disorder and prince regents as common features of their reigns

Abstract Humanity is sporadically subjected to leaders with deviant behavior, ego problems, or psychiatric disorders, potentially leading to social instability. Bipolar disorder is not common in all populations, but, coincidentally, studies suggest that it affected two sovereigns that were contemporaries, King George III of England, who died 201 years ago, and Queen Maria I of Portugal, who died 205 years ago. They lived during a time when Europe was in turmoil with the French Revolution and Napoleonic Wars, which also coincided with the rise of psychiatry. Both monarchs were forced to have prince regents rule in their place, due to their emotional decline, and they shared the same medical consultant, Francis Willis.

Transport properties in multilayer adsorption of dimers.

In this paper, we study the transport properties (percolation and conductivity) of a two-dimensional structure created by depositing dimers on a one-dimensional substrate where multilayer deposition is allowed. Specifically, we are interested in studying how the mentioned properties vary as a function of the height of the multilayer. The critical parameters of the percolation transition are calculated using finite-size scaling analysis, obtaining the scaling laws for the probability of percolation and the conductivity of the system. To calculate the electrical conductivity of the multilayer, we use the Frank-Lobb algorithm.

Unfolding of crumpled thin sheets.

Crumpled thin sheets are complex fractal structures whose physical properties are influenced by a hierarchy of ridges. In this paper, we report experiments that measure the stress-strain relation and show the coexistence of phases in the stretching of crumpled surfaces. The pull stress showed a change from a linear Hookean regime to a sublinear scaling with an exponent of 0.65±0.03, which is identified with the Hurst exponent of the crumpled sheets. The stress fluctuations are studied. The statistical distribution of force peaks is analyzed. It is shown that the unpacking of crumpled sheets is guided by a hierarchical order of ridges.

Durability assessment of external thermal insulation composite systems in urban and maritime environments.

External Thermal Insulation Composite Systems (ETICS) are multilayer solutions which provide an enhanced thermal performance to the building envelope. However, significant anomalies can be detected on ETICS facades, in some cases shortly after the application of these systems. This study intends to evaluate and compare the durability of six commercially available ETICS after two years of outdoor exposure at both urban and maritime conditions in Portugal. The systems were characterized by means of non-destructive testing (i.e., visual and microscopic assessment, water transport properties, thermal conductivity, surface roughness), thus allowing to evaluate the performance loss throughout natural aging. The bio-susceptibility and aesthetic properties (color and gloss) were also investigated. Results showed that the performance and durability of the complete system is significantly affected by the rendering system formulation. The lime-based specimens obtained the highest rate of mold development after one year of aging in a maritime environment, becoming considerably darker and with lower surface gloss. Fungal analysis of this darkish stained area indicated the presence of mold species of the genera Alternaria, Didymella, Cladosporium and Epicoccum, and yeasts of the genera Vishniacozyma and Cystobasidium. An increase of both capillary water absorption and water vapor permeability was also registered for the aged lime-based specimens. Acrylic-based systems obtained lower capillary water absorption after aging and greater dirt deposition on their surfaces, especially in urban conditions. These systems had also higher color variation and surface gloss decrease and slightly higher mold growth, when compared with those aged in a maritime environment. Finally, no mold growth was detected on the silicate-based specimens after two years of aging. However, these specimens obtained higher capillary water absorption and lower vapor permeability after aging, possibly leading to moisture accumulation within the system. Results contribute towards the development of ETICS with enhanced performance and durability.

Herd immunity under individual variation and reinfection.

We study a susceptible-exposed-infected-recovered (SEIR) model considered by Aguas et al. (In: Herd immunity thresholds for SARS-CoV-2 estimated from unfolding epidemics, 2021), Gomes et al. (In: J Theor Biol. 540:111063, 2022) where individuals are assumed to differ in their susceptibility or exposure to infection. Under this heterogeneity assumption, epidemic growth is effectively suppressed when the percentage of the population having acquired immunity surpasses a critical level - the herd immunity threshold - that is lower than in homogeneous populations. We derive explicit formulas to calculate herd immunity thresholds and stable configurations, especially when susceptibility or exposure are gamma distributed, and explore extensions of the model.