A new subjective well-being index using anchored best-worst scaling.

Subjective well-being (SWB) describes an individual's life evaluation. Direct elicitation methods for SWB via rating scales do not force individuals to trade-off among life domains, whilst best-worst scaling (BWS) approaches only provide relative measures. This paper instead offers a dual-response BWS task, where respondents nominate areas of most and least importance and satisfaction with respect to 11 SWB domains, whilst also eliciting anchoring points to obtain an absolute measure of domain satisfaction. Combining domain satisfaction and importance produces a robust measure of individual SWB, but statistically unique relative to other life satisfaction measures utilizing single- and multi-item ratings, including global satisfaction and those aggregated over SWB domains, as well as eudemonia. Surveying 2500 Australians reveals anchored-BWS improves discrimination amongst domains in terms of importance and satisfaction, illustrating its value as a diagnostic tool for SWB measurement to focus services, policy, and initiatives in areas to most impact wellbeing. This includes highlighting a major discrepancy between health satisfaction and importance, whilst also reporting that SWB is significantly lower for Indigenous, unemployed, middle-aged, males and lower income groups.

Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure.

Approximately 3.3 billion people live with the threat of Plasmodium vivax malaria. Infection can result in liver-localized hypnozoites, which when reactivated cause relapsing malaria. This work demonstrates that an enzyme-cleavable polymeric prodrug of tafenoquine addresses key requirements for a mass administration, eradication campaign: excellent subcutaneous bioavailability, complete parasite control after a single dose, improved therapeutic window compared to the parent oral drug, and low cost of goods sold (COGS) at less than $1.50 per dose. Liver targeting and subcutaneous dosing resulted in improved liver:plasma exposure profiles, with increased efficacy and reduced glucose 6-phosphate dehydrogenase-dependent hemotoxicity in validated preclinical models. A COGS and manufacturability analysis demonstrated global scalability, affordability, and the ability to redesign this fully synthetic polymeric prodrug specifically to increase global equity and access. Together, this polymer prodrug platform is a candidate for evaluation in human patients and shows potential for P. vivax eradication campaigns.

Artificial flowers as a tool for investigating multimodal flower choice in wild insects.

Flowers come in a variety of colours, shapes, sizes and odours. Flowers also differ in the quality and quantity of nutritional reward they provide to entice potential pollinators to visit. Given this diversity, generalist flower-visiting insects face the considerable challenge of deciding which flowers to feed on and which to ignore. Working with real flowers poses logistical challenges due to correlations between flower traits, maintenance costs and uncontrolled variables. Here, we overcome this challenge by designing multimodal artificial flowers that varied in visual, olfactory and reward attributes. We used artificial flowers to investigate the impact of seven floral attributes (three visual cues, two olfactory cues and two rewarding attributes) on flower visitation and species richness. We investigated how flower attributes influenced two phases of the decision-making process: the decision to land on a flower, and the decision to feed on a flower. Artificial flowers attracted 890 individual insects representing 15 morphospecies spanning seven arthropod orders. Honeybees were the most common visitors accounting for 46% of visitors. Higher visitation rates were driven by the presence of nectar, the presence of linalool, flower shape and flower colour and was negatively impacted by the presence of citral. Species richness was driven by the presence of nectar, the presence of linalool and flower colour. For hymenopterans, the probability of landing on the artificial flowers was influenced by the presence of nectar or pollen, shape and the presence of citral and/or linalool. The probability of feeding increased when flowers contained nectar. For dipterans, the probability of landing on artificial flowers increased when the flower was yellow and contained linalool. The probability of feeding increased when flowers contained pollen, nectar and linalool. Our results demonstrate the multi-attribute nature of flower preferences and highlight the usefulness of artificial flowers as tools for studying flower visitation in wild insects.

Neuroanatomy of the crocodylian Tomistoma dowsoni from the Miocene of North Africa provides insights into the evolutionary history of gavialoids.

The interrelationships of the extant crocodylians Gavialis gangeticus and Tomistoma schlegelii have been historically disputed. Whereas molecular analyses indicate a sister taxon relationship between these two gavialoid species, morphological datasets typically place Gavialis as the outgroup to all other extant crocodylians. Recent morphological-based phylogenetic analyses have begun to resolve this discrepancy, recovering Gavialis as the closest living relative of Tomistoma; however, several stratigraphically early fossil taxa are recovered as closer to Gavialis than Tomistoma, resulting in anomalously early divergence timings. As such, additional morphological data might be required to resolve these remaining discrepancies. 'Tomistoma' dowsoni is an extinct species of gavialoid from the Miocene of North Africa. Utilising CT scans of a near-complete, referred skull, we reconstruct the neuroanatomy and neurosensory apparatus of 'Tomistoma' dowsoni. Based on qualitative and quantitative morphometric comparisons with other crocodyliforms, the neuroanatomy of 'Tomistoma' dowsoni is characterised by an intermediate morphology between the two extant gavialoids, more closely resembling Gavialis. This mirrors the results of recent studies based on the external anatomy of these three species and other fossil gavialoids. Several neuroanatomical features of these species appear to reflect ecological and/or phylogenetic signals. For example, the 'simple' morphology of their neurosensory apparatus is broadly similar to that of other long and narrow-snouted (longirostrine), aquatic crocodyliforms. A dorsoventrally short, anteroposteriorly long endosseous labyrinth is also associated with longirostry. These features indicate that snout and skull morphology, which are themselves partly constrained by ecology, exert an influence on neuroanatomical morphology, as has also been recognised in birds and turtles. Conversely, the presence of a pterygoid bulla in Gavialis and several extinct gavialoids, and its absence in Tomistoma schlegelii, could be interpreted as a phylogenetic signal of crocodylians more closely related to Gavialis than to Tomistoma. Evaluation of additional fossil gavialoids will be needed to further test whether these and other neuroanatomical features primarily reflect a phylogenetic or ecological signal. By incorporating such previously inaccessible information of extinct and extant gavialoids into phylogenetic and macroecological studies, we can potentially further constrain the clade's interrelationships, as well as evaluate the timing and ecological association of the evolution of these neuroanatomical features. Finally, our study supports recent phylogenetic analyses that place 'Tomistoma' dowsoni as being phylogenetically closer to Gavialis gangeticus than to Tomistoma schlegelii, indicating the necessity of a taxonomic revision of this fossil species.

Extreme temperatures, mortality, and adaptation: Evidence from the county level in China.

Extreme temperatures are known to cause adverse health outcomes. Yet knowledge on the magnitude of this effect in developing countries is limited due to data availability and reliability issues. Collecting data for 2872 counties in China, we estimate the effects of daily temperatures on the monthly mortality rate. The results indicate that an additional day for which the maximum temperature is 38°C or above on average increases the monthly mortality rate by about 1.7% relative to if that day's maximum temperature had been in the range 16-21°C. This is after deducting deaths harvested from the subsequent month. Higher gross domestic product per capita at the county level is associated with lower mortality effects of hot and cold days. Improved dwelling conditions are found to be associated with a lower mortality effect of hot days and improved local healthcare infrastructure to be associated with a lower mortality effect of cold days. In the absence of strong adaptation efforts, the estimates suggest net upward pressure on annual mortality rates over coming decades in many populous counties, especially under more extreme climate change scenarios.

Why do experts disagree? The development of a taxonomy.

People are increasingly exposed to conflicting health information and must navigate this information to make numerous decisions, such as which foods to consume, a process many find difficult. Although some consumers attribute these disagreements to aspects related to uncertainty and complexity of research, many use a narrower set of credibility-based explanations. Experts' views on disagreements are underinvestigated and lack explicit identification and classification of the differences in causes for disagreement. Consequently, there is a gap in existing literature to understand the range of reasons for these contradictions. Combining the findings from a literature study and expert interviews, a taxonomy of disagreements was developed. It identifies 10 types of disagreement classified under three dimensions: informant-, information- and uncertainty-related causes for disagreement. The taxonomy may assist with adoption of more effective strategies to deal with conflicting information and contributes to research and practice of science communication in the context of disagreement.

Teachers' Experiences of Emergency Remote Schooling During the Pandemic: Drivers for Student and Teacher Wellbeing.

This article discusses findings from a recent survey (n = 297) of teachers' views of both their own and their students' experiences during the 2021 enforced emergency remote schooling period occurring in New South Wales Australia, due to the COVID-19 pandemic. The quantitative analysis reported here explores teachers' views regarding teaching and learning during this challenging period. It identifies three latent constructs, learning, assessment, and interaction, and then uses structural equation modelling to identify the perceived impact of these constructs on student and teacher wellbeing. The remote schooling period had a significant negative impact for teachers and their students across a range of elements of teaching and learning, as well as wellbeing. Student learning experiences and their peer interactions were found to be strong predictors of students' wellbeing outcomes. Assessment design and teachers' feedback to students were significant in predicting levels of teacher wellbeing. Future research directions are also provided.

Predicting the efficiency of oxygen-evolving electrolysis on the Moon and Mars.

Establishing a permanent human presence on the Moon or Mars requires a secure supply of oxygen for life support and refueling. The electrolysis of water has attracted significant attention in this regard as water-ice may exist on both the Moon and Mars. However, to date there has been no study examining how the lower gravitational fields on the Moon and Mars might affect gas-evolving electrolysis when compared to terrestrial conditions. Herein we provide experimental data on the effects of gravitational fields on water electrolysis from 0.166 g (lunar gravity) to 8 g (eight times the Earth's gravity) and show that electrolytic oxygen production is reduced by around 11% under lunar gravity with our system compared to operation at 1 g. Moreover, our results indicate that electrolytic data collected using less resource-intensive ground-based experiments at elevated gravity (>1 g) may be extrapolated to gravitational levels below 1 g.

Fuel prices and road deaths: Motorcyclists are different.

This study estimates the effect of gasoline prices on road deaths by vehicle mode using annual data for 62 countries for 2000-2018 and all states of the United States (US) for 1998-2018. Higher gasoline prices are associated with fewer overall road deaths. The proportional effect on motorcyclist deaths tends to be smaller or even have the opposite sign, especially in countries that are not highly dependent on motorcycles. For the US, a positive effect of gasoline prices on motorcyclist deaths is found, with an elasticity of about 0.3. There is also a positive relationship between gasoline prices and motorcycle registrations in the US. The results confirm that additional attention towards motorcyclist safety is warranted in times of high fuel prices.

Enablers and barriers to COVID-19 vaccine uptake: An international study of perceptions and intentions.

The development of COVID-19 vaccines is occurring at unprecedented speeds, but require high coverage rates to be successful. This research examines individuals' psychological beliefs that may act as enablers and barriers to vaccination intentions. Using the health beliefs model as a guide to our conceptual framework, we explore factors influencing vaccine hesitancy and health beliefs regarding risks and severity of the disease, along with individual variables such as income, age, religion, altruism, and collectivism. A questionnaire using newly created measures for various antecedents provided 4303 usable responses from Australia, Canada, England, New Zealand, and the United States. A factor analytic and structural equation model indicates that trust in vaccine approval, the perceived effectiveness of the vaccine for protecting others, and conspiracy beliefs are the most significant drivers of intentions to vaccinate. Older people, those seeking employment, and those who have received a recent influenza vaccine are more likely to be vaccinated against COVID-19. The findings have implications for improving communication strategies targeting individuals about the merits of vaccination, particularly focusing on younger individuals and expanded message framing to include altruistic considerations, and to improve government transparency regarding the effectiveness and side effects of vaccines.

An investigation of psychological responses to COVID-19 in Irish healthcare workers: longitudinal quantitative and nested qualitative study.

COVID-19 is an unprecedent occurrence in modern times and individuals who work within healthcare settings, face a broad array of challenges in responding to this worldwide event. Key information on the psychosocial responses of such healthcare workers (HCWs) in the context of COVID-19 is limited and in particular there is a need for studies that utilise longitudinal methods, an overarching theoretical model, and use of a cohort of participants within a defined geographical area across acute and community settings. The work packages making up the current research project use quantitative and qualitative methods to examine the psychological sequelae for HCWs in the context of COVID-19 in geographically adjacent healthcare areas (South and Mid-West of Ireland) across four time points (induction, 3 months, 6 months, and 1 year follow-up). The quantitative arm of the project (WP 1) utilises the Common-Sense Model of Self-Regulation (CSM-SR) and examines a number of key psychological factors pertinent to this model including perceptions about COVID-19 and infection more generally, coping, formal and informal support and a number of impact variables including mood, sleep quality, and perceptions of stigma. The qualitative study (WP 2) will address HCWs experiences of working during the pandemic, ascertain any additional areas of psychological functioning, environmental and workplace factors and resources that may be utilised by HCWs and that are not assessed by the quantitative study protocol, focusing particularly on those staff groups typically underrepresented in previous studies.

SARS-CoV-2 infection in general practice in Ireland: a seroprevalence study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing in community settings may help us better understand the immune response to this virus and, therefore, help guide public health efforts. AIM: To conduct a seroprevalence study of immunoglobulin G (IgG) antibodies in Irish GP clinics. DESIGN & SETTING: Participants were 172 staff and 799 patients from 15 general practices in the Midwest region of Ireland. METHOD: This seroprevalence study utilised two manufacturers' point-of-care (POC) SARS-CoV-2 immunoglobulin M (IgM)-IgG combined antibody tests, which were offered to patients and staff in general practice from 15 June to 10 July 2020. RESULTS: IgG seroprevalence was 12.6% in patients attending general practice and 11.1% in staff working in general practice, with administrative staff having the lowest seroprevalence at 2.5% and nursing staff having the highest at 17.6%. Previous symptoms suggestive of COVID-19 and history of a polymerase chain reaction (PCR) test were associated with higher seroprevalence. IgG antibodies were detected in approximately 80% of participants who had a previous PCR-confirmed infection. Average length of time between participants' positive PCR test and positive IgG antibody test was 83 days. CONCLUSION: Patients and healthcare staff in general practice in Ireland had relatively high rates of IgG to SARS-CoV-2 compared with the national average between 15 June and 10 July 2020 (1.7%). Four-fifths of participants with a history of confirmed COVID-19 disease still had detectable antibodies an average of 12 weeks post-infection. While not proof of immunity, SARS-CoV-2 POC testing can be used to estimate IgG seroprevalence in general practice settings.

Liver-targeted polymeric prodrugs of 8-aminoquinolines for malaria radical cure.

Primaquine and tafenoquine are the two 8-aminoquinoline (8-AQ) antimalarial drugs approved for malarial radical cure - the elimination of liver stage hypnozoites after infection with Plasmodium vivax. A single oral dose of tafenoquine leads to high efficacy against intra-hepatocyte hypnozoites after efficient first pass liver uptake and metabolism. Unfortunately, both drugs cause hemolytic anemia in G6PD-deficient humans. This toxicity prevents their mass administration without G6PD testing given the approximately 400 million G6PD deficient people across malarial endemic regions of the world. We hypothesized that liver-targeted delivery of 8-AQ prodrugs could maximize liver exposure and minimize erythrocyte exposure to increase their therapeutic window. Primaquine and tafenoquine were first synthesized as prodrug vinyl monomers with self-immolative hydrolytic linkers or cathepsin-cleavable valine-citrulline peptide linkers. RAFT polymerization was exploited to copolymerize these prodrug monomers with hepatocyte-targeting GalNAc monomers. Pharmacokinetic studies of released drugs after intravenous administration showed that the liver-to-plasma AUC ratios could be significantly improved, compared to parent drug administered orally. Single doses of the liver-targeted, enzyme-cleavable tafenoquine polymer were found to be as efficacious as an equivalent dose of the oral parent drug in the P. berghei causal prophylaxis model. They also elicited significantly milder hemotoxicity in the humanized NOD/SCID mouse model engrafted with red blood cells from G6PD deficient donors. The clinical application is envisioned as a single subcutaneous administration, and the lead tafenoquine polymer also showed excellent bioavailability and liver-to-blood ratios exceeding the IV administered polymer. The liver-targeted tafenoquine polymers warrant further development as a single-dose therapeutic via the subcutaneous route with the potential for broader patient administration without a requirement for G6PD diagnosis.

Effects of anxiety on preferences for generic medicines in Australia.

Generic medicines have been available to consumers for ∼40 years, with varying degrees of uptake in different countries. Despite offering equivalent therapeutic qualities, generic medicines still struggle to be accepted by consumers. This study examines the role of a consumer's affective state and framing effects on the purchase of a branded versus a generic pharmaceutical product. These issues are examined in an experiment, with independent manipulations of consumer anxiety levels and the framing of generic alternatives by the pharmacist. The sample comprised 426 men and women within Australia who completed an online survey with a scenario of purchasing a pharmaceutical after visiting a General Practitioner. Results indicate that those consumers experiencing higher levels of anxiety and where the doctor prescribed the branded medicine are more likely to choose branded medicines over cheaper, generic alternatives. The effect of framing the generic alternative as either 'generic' or 'cheaper' was not significant.

An international experience of electronic communication and implementation of eHealth solutions in a vascular surgery clinic.

INTRODUCTION: Communication is key to any successful relationship with the patient-physician partnership being no different. Recent advances in technology have provided us with an array of new communication tools such as the mobile phone, computer, internet, and email. This new technology has revolutionized communications; however, limitations to their widespread use include access, literacy, and willingness for both the physician and patient to change. METHODS: To gather international data, questionnaires were completed by patients attending vascular surgery outpatient clinics in hospitals in Ireland and Canada. RESULTS: Five hundred ninety-seven patients participated in the study. Of the participants, 83.2% were over 50 years old. The mean age was 63.1 years, with a range of 18-95 years. Overall, home phone call was the most preferred method of communication with 41.0% of patients selecting this option. Of the patients, 82.4% had a mobile phone but just 48.5% use text message. In those over the age of 70, 72.1% use a mobile phone and just 25.3% use text message. Of the participants, 64.1% had access to a computer, and 67.2% had access to the internet with a decline in the usage of both with increasing age. DISCUSSION: Within this patient population, the use of technologies decreases with increasing age of the patients. This demonstrates a large population of service users who are contented with conventional methods of communication. Change within healthcare ICT is inevitable, and therefore, these patients need to be guided and educated to allow a smooth transition from the old to the new.

Autologous bone marrow mesenchymal stromal cell therapy for "no-option" critical limb ischemia is limited by karyotype abnormalities.

BACKGROUND: Critical limb ischemia (CLI) is the most severe manifestation of peripheral vascular disease. Revascularization is the preferred therapy, but it is not achievable in 25%-40% of patients due to diffuse anatomic distribution of the disease or medical comorbidities. No-option CLI represents an unmet medical need. Mesenchymal stromal cells (MSCs) may provide salvage therapy through their angiogenic and tissue-trophic properties. This article reports a phase 1b clinical study examining the safety and feasibility of intramuscular transplantation of autologous bone-marrow MSCs for patients with no-option CLI. METHODS: Twelve patients were enrolled in the clinical trial, and nine proceeded to bone marrow aspiration and culture expansion of MSCs. RESULTS: A high rate of karyotype abnormality (>30%) was detected in the produced cell batches, resulting in failure of release for clinical administration. Four patients were treated with the investigational medicinal product (IMP), three with a low dose of 20 × 106 MSCs and one with a mid-dose of 40 × 106 MSCs. There were no serious adverse events related to trial interventions, including bone marrow aspiration, IMP injection or therapy. CONCLUSIONS: The results of this trial conclude that an autologous cell therapy approach with MSCs for critical limb ischemia is limited by the high rate of karyotype abnormalities.

A Systematic Review and Meta-analysis of Thrombotic Events Following Endovenous Thermal Ablation of the Great Saphenous Vein.

OBJECTIVES: A systematic review and meta-analysis was performed to determine the incidence of thrombotic events following great saphenous vein (GSV) endovenous thermal ablation (EVTA). METHODS: MEDLINE, Embase and conference abstracts were searched. Eligible studies were randomised controlled trials and case series that included at least 100 patients who underwent GSV EVTA (laser ablation or radiofrequency ablation [RFA]) with duplex ultrasound (DUS) within 30 days. The systematic review focused on the complications of endovenous heat induced thrombosis (EHIT), deep venous thrombosis (DVT), and pulmonary embolism (PE). The primary outcome for the meta-analysis was deep venous thrombotic events which were defined as DVT or EHIT Type 2, 3, or 4. Secondary outcomes for the meta-analysis were EHIT Type 2, 3, or 4, DVT and PE. Subgroup analyses were performed for both the RFA and EVLA groups. Pooled proportions were calculated using random effects modelling. RESULTS: Fifty-two studies (16,398 patients) were included. Thrombotic complications occurred infrequently. Deep venous thrombotic events occurred in 1.7% of cases (95% CI 0.9-2.7%) (25 studies; 10,012 patients; 274 events). EHIT Type 2, 3, or 4 occurred in 1.4% of cases (95% CI 0.8-2.3%) (26 studies; 10,225 patients; 249 events). DVT occurred in 0.3% of cases (95% CI = 0.2%-0.5%) (49 studies; 15,676 patients; 48 events). PE occurred in 0.1% of cases (95% CI = 0.1-0.2%) (29 studies; 8223 patients; 3 events). Similar results were found when the RFA and EVLA groups were analysed separately. CONCLUSION: Thrombotic events occur infrequently following GSV EVTA. Given the large numbers of procedures worldwide and the potential for serious consequences, further research is needed on the burden of these complications and their management.

The impact of front-of-pack marketing attributes versus nutrition and health information on parents' food choices.

Front-of-pack attributes have the potential to affect parents' food choices on behalf of their children and form one avenue through which strategies to address the obesogenic environment can be developed. Previous work has focused on the isolated effects of nutrition and health information (e.g. labeling systems, health claims), and how parents trade off this information against co-occurring marketing features (e.g. product imagery, cartoons) is unclear. A Discrete Choice Experiment was utilized to understand how front-of-pack nutrition, health and marketing attributes, as well as pricing, influenced parents' choices of cereal for their child. Packages varied with respect to the two elements of the Australian Health Star Rating system (stars and nutrient facts panel), along with written claims, product visuals, additional visuals, and price. A total of 520 parents (53% male) with a child aged between five and eleven years were recruited via an online panel company and completed the survey. Product visuals, followed by star ratings, were found to be the most significant attributes in driving choice, while written claims and other visuals were the least significant. Use of the Health Star Rating (HSR) system and other features were related to the child's fussiness level and parents' concerns about their child's weight with parents of fussy children, in particular, being less influenced by the HSR star information and price. The findings suggest that front-of-pack health labeling systems can affect choice when parents trade this information off against marketing attributes, yet some marketing attributes can be more influential, and not all parents utilize this information in the same way.

Can a Neutrophil-Lymphocyte Ratio Derived from Preoperative Blood Tests Predict Arteriovenous Fistula Maturation?

BACKGROUND: To evaluate the association between inflammatory markers expressed as neutrophil-lymphocyte ratio (NLR) and process of arteriovenous fistula (AVF) maturation. METHODS: A retrospective review of patients with end-stage renal disease referred for formation of a new AVF in one center. Patients referred to the vascular service in the University Hospital of Limerick for creation of vascular access between 2009 and 2013. The association between NLR, calculated from preoperative blood tests, and functional fistula maturation, as determined by successful use of the AVF for 6 consecutive hemodialysis sessions, was investigated using univariate and logistic regression analyses. A logistic regression analysis was carried out to assess potential influence from other factors related to AVF maturation. Stepwise regression test was performed including the NLR. RESULTS: Overall AVF functional maturation rate in our study was 53.7% (66/123). Patients with matured AVFs had an NLR of 4.850 (1.8-15.7) compared with 3.554 (1.7-15.0); this difference was found to be significant (P = 0.024). Female gender (P = 0.008) and a history of kidney transplant (P = 0.004) were the only independent factors of fistula maturation outcome in a logistic regression model. CONCLUSION: Increased level of NLR was found to be associated with fistula maturation; however, more studies are needed to validate this finding.