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Abstract Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta‐lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure. An ex vivo study was undertaken using CPB devices primed and then dosed with cefazolin and samples were obtained over 1 hour of recirculation. Twelve experimental runs were conducted using different CPB device sizes (neonate, infant, child, and adult), device coatings (Xcoating™, Rheoparin®, PH.I.S.I.O), and priming solutions. The time course of saturable binding, using Bmax (binding capacity), Kd (dissociation constant), and T2off (half‐time of dissociation), described cefazolin adsorption. Bmax estimates for the device sizes were neonate 40.0 mg (95% CI 24.3, 67.4), infant 48.6 mg (95% CI 5.97, 80.2), child 77.8 mg (95% CI 54.9, 103), and adult 196 mg (95% CI 191, 199). The Xcoating™ Kd estimate was 139 mg/L (95% CI 27.0, 283) and the T2off estimate was 98.4 min (95% CI 66.8, 129). The Rheoparin® and PH.I.S.I.O coatings had similar binding parameters with Kd and T2off estimates of 0.169 mg/L (95% CI 0.01, 1.99) and 4.94 min (95% CI 0.17, 59.4). The Bmax was small (

Abstract People’s negative attitudes to vaccines can be motivated by psychological factors—such as fears, ideological beliefs, and cognitive patterns—known as ‘attitude roots’. This study had two primary objectives: (1) to identify which of 11 known attitude roots are featured in individuals’ self-expressed reasons for negative vaccine attitudes (i.e., a linguistic analysis); (2) to explore how attitude roots present in self-expressed texts are linked to specific psychological measures. To achieve Objective 1, our study collected data from December 2022 to January 2023 from 556 participants from the US, who wrote texts to explain the reasons for their negative vaccine attitudes. The texts encompassed 2327 conceptually independent units of anti-vaccination argumentation, that were each coded for its attitude root(s) by at least two psychological experts. By allowing participants to spontaneously express their attitudes in their own words, we were able to observe how this differed from what participants reported to endorse when presented with a list of arguments. We found that there were four groups of attitude roots based on linguistic similarity in self-expression. In addition, latent class analysis of participants’ coded texts identified three distinct groups of participants that were characterised by their tendency to express combinations of arguments related to (1) fears, (2) anti-scientific conceptions, and (3) politicised perspectives. To achieve Objective 2, we collected participants’ responses to 11 validated measures of psychological constructs expected to underlie the respective 11 attitude roots, and used a correlational design to investigate how participants’ self-expressed attitude roots were linked to these measures. Logistic regressions showed that an expected psychological construct was the strongest, and significant, predictor for expression of three out of the four attitude root groups. We discuss the implications of these findings for health communicators and practitioners.

Abstract Background Healthcare professionals (HCPs) can play an important role in encouraging patients and their caregivers to be vaccinated. The objective of this qualitative study was to investigate HCPs’ perspectives on challenges in vaccine communication and unmet training needs in this domain. Methods Semi-structured interviews were conducted with 41 HCPs (mainly nurses and physicians) with vaccination roles (23 in England; 18 in France), gathering information on: (1) HCPs’ approach to vaccine conversations with patients; (2) Challenges of communicating about vaccines; (3) Vaccine-related training and learning resources available to HCPs, and; (4) HCPs’ training needs around vaccine communication. Results HCPs described a range of communication experiences that indicated insufficient time, information, and skills to confidently navigate difficult conversations with vaccine-hesitant patients. Communication skills were especially important to avoid conflict that could potentially damage the patient-provider relationship. Some HCPs interviewed had received communication training, but for most, this training was not specific to vaccination. Although general communication skills were transferable to vaccine conversations, most HCPs welcomed specific training and informational resources to support countering patients’ misconceptions or misinformation about vaccines. Conclusions HCPs would benefit from training tailored to address vaccine communication with patients, and this should be part of a systemic approach that also provides time and space to have effective vaccine conversations.

Abstract Background Stigma, lack of trust in authorities, and poor knowledge can prevent health-seeking behaviour, worsen physical and mental health, and undermine efforts to control transmission during disease outbreaks. These factors are particularly salient with diseases such as mpox, for which 96% of cases in the 2022–2023 UK outbreak were identified among gay, bisexual, queer and men who have sex with men (MSM). This study explored stigma and health-seeking behaviour in Liverpool through the lens of the recent mpox outbreak. Methods Primary sources of data were interviews with national and regional key informants involved in the mpox response, and participatory workshops with priority populations. Workshop recruitment targeted Grindr users (geosocial dating/hookup app) and at risk MSM; immigrant, black and ethnic minority MSM; and male sex workers in Liverpool. Data were analysed using a deductive framework approach, building on the Health Stigma and Discrimination Framework. Results Key informant interviews (n = 11) and five workshops (n = 15) were conducted. There were prevalent reports of anticipated and experienced stigma due to mpox public health messaging alongside high demand and uptake of the mpox vaccine and regular attendance at sexual health clinics. Respondents believed the limited impact of stigma on health-seeking behaviour was due to actions by the LGBTQ + community, the third sector, and local sexual health clinics. Key informants from the LGBTQ + community and primary healthcare felt their collective action to tackle mpox was undermined by central public health authorities citing under-resourcing; a reliance on goodwill; poor communication; and tokenistic engagement. Mpox communication was further challenged by a lack of evidence on disease transmission and risk. This challenge was exacerbated by the impact of the COVID-19 pandemic on the scientific community, public perceptions of infectious disease, and trust in public health authorities. Conclusions The LGBTQ + community and local sexual health clinics took crucial actions to counter stigma and support health seeking behaviour during the 2022–2023 UK mpox outbreak. Lessons from rights based and inclusive community-led approaches during outbreaks should be heeded in the UK, working towards more meaningful and timely collaboration between affected communities, primary healthcare, and regional and national public health authorities.

Abstract Modeling the relationships between covariates and pharmacometric model parameters is a central feature of pharmacometric analyses. The information obtained from covariate modeling may be used for dose selection, dose individualization, or the planning of clinical studies in different population subgroups. The pharmacometric literature has amassed a diverse, complex, and evolving collection of methodologies and interpretive guidance related to covariate modeling. With the number and complexity of technologies increasing, a need for an overview of the state of the art has emerged. In this article the International Society of Pharmacometrics (ISoP) Standards and Best Practices Committee presents perspectives on best practices for planning, executing, reporting, and interpreting covariate analyses to guide pharmacometrics decision making in academic, industry, and regulatory settings.

Summary: Background: Argentina's smoking rates remain high. We aim to estimate Argentina age-specific histories of smoking initiation, cessation, prevalence, and intensity by birth-cohort to inform policy interventions. Methods: Modeling study. Data from three Argentinian nationally representative surveys conducted from 2004 to 2018 (n = 268,193) were used to generate smoking histories. The Cancer Intervention and Surveillance Modeling (CISNET) Network Lung Working Group age, period, and cohort modeling approach was used to calculate smoking initiation and cessation probabilities, ever and current smoking prevalence, and intensity (cigarettes per day, CPD) by age, sex, and birth cohort from 1950 to 2018. Findings: Ever smoking prevalence increases with age up to 25 and decreases with birth cohorts after 1990. Smoking initiation peaks between 15 and 18 years of age. Among females, initiation probabilities increased until the 1955 cohort, reaching a second peak in 1980–85 cohorts and declining thereafter. Males have higher initiation probabilities than females. Among males, initiation has decreased since the 1950 birth cohort, with a slight increase around the 1985 cohort. Current smoking prevalence has been decreasing since the 1960 birth cohort, except for a peak in 1980–85 cohorts. Cessation increases with age. Mean CPD increases with age and peaks around age 40, appearing flat in females since the 1985 cohort. Interpretation: Recent birth cohorts seem to be experiencing lower rates of initiation, stable rates of quitting and lower current and ever smoking prevalence. The stabilization of cessation probabilities and mean CPD indicate the need to strengthen existing tobacco control measures and advance new ones. Funding: NIH/NCI U01CA253858 grant.

Arsenic (As) contamination of agricultural soils poses a serious threat to crop productivity and food safety. Zinc oxide nanoparticles (ZnONPs) have emerged as a potential amendment for mitigating the adverse effects of As stress in plants. Soybean crop is mostly grown on marginalized land and is known for high accumulation of As in roots than others tissue. Therefore, this study aimed to elucidate the underlying mechanisms of ZnONPs in ameliorating arsenic toxicity in soybean. Our results demonstrated that ZnOB significantly improved the growth performance of soybean plants exposed to arsenic. This improvement was accompanied by a decrease (55%) in As accumulation and an increase in photosynthetic efficiency. ZnOB also modulated hormonal balance, with a significant increase in auxin (149%), abscisic acid (118%), gibberellin (160%) and jasmonic acid content (92%) under As(V) stress assuring that ZnONPs may enhance root growth and development by regulating hormonal signaling. We then conducted a transcriptomic analysis to understand further the molecular mechanisms underlying the NPs-induced As(V) tolerance. This analysis identified genes differentially expressed in response to ZnONPs supplementation, including those involved in auxin, abscisic acid, gibberellin, and jasmonic acid biosynthesis and signaling pathways. Weighted gene co-expression network analysis identified 37 potential hub genes encoding stress responders, transporters, and signal transducers across six modules potentially facilitated the efflux of arsenic from cells, reducing its toxicity. Our study provides valuable insights into the molecular mechanisms associated with metalloid tolerance in soybean and offers new avenues for improving As tolerance in contaminated soils.

Diaphorina citri serves as the primary vector for ‘Candidatus Liberibacter asiaticus (CLas),’ the bacterium associated with the severe Asian form of huanglongbing. CLas-positive D. citri are more fecund than their CLas-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone (DcAKH) and its receptor (DcAKHR) were essential for increasing lipid metabolism and fecundity in response to CLas infection in D. citri. Knockdown of DcAKH and DcAKHR not only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity and CLas titer in ovaries. Combined in vivo and in vitro experiments showed that miR-34 suppresses DcAKHR expression by binding to its 3’ untranslated region, whilst overexpression of miR-34 resulted in a decline of DcAKHR expression and CLas titer in ovaries and caused defects that mimicked DcAKHR knockdown phenotypes. Additionally, knockdown of DcAKH and DcAKHR significantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor, methoprene-tolerant (DcMet), and the transcription factor, Krüppel homolog 1 (DcKr-h1), that acts downstream of it, as well as the egg development related genes vitellogenin 1-like (DcVg-1-like), vitellogenin A1-like (DcVg-A1-like) and the vitellogenin receptor (DcVgR). As a result, CLas hijacks AKH/AKHR-miR-34-JH signaling to improve D. citri lipid metabolism and fecundity, while simultaneously increasing the replication of CLas, suggesting a mutualistic interaction between CLas and D. citri ovaries.

Background Healthcare professionals (HCPs) play an important role in vaccination; those with low confidence in vaccines are less likely to recommend them to their patients and to be vaccinated themselves. The study’s purpose was to adapt and validate long- and short-form versions of the International Professionals’ Vaccine Confidence and Behaviors (I-Pro-VC-Be) questionnaire to measure psychosocial determinants of HCPs’ vaccine confidence and their associations with vaccination behaviors in European countries. Research design and methods After the original French-language Pro-VC-Be was culturally adapted and translated, HCPs involved in vaccination (mainly GPs and pediatricians) across Germany, Finland, France, and Portugal completed a cross-sectional online survey in 2022. A 10-factor multigroup confirmatory factor analysis (MG-CFA) of the long-form (10 factors comprising 34 items) tested for measurement invariance across countries. Modified multiple Poisson regressions tested the criterion validity of both versions. Results 2,748 HCPs participated. The 10-factor structure fit was acceptable to good everywhere. The final MG-CFA model confirmed strong factorial invariance and showed very good fit. The long- and short-form I-Pro-VC-Be had good criterion validity with vaccination behaviors. Conclusion This study validates the I-Pro-VC-Be among HCPs in four European countries; including long- and short-form tools for use in research and public health.

Molecular confirmation of the presence of the tomato leafminer, Phthorimaea (Tuta) absoluta Meyrick, 1917 (Lepidoptera: Gelechiidae), in the Paksong region of the Bolaven Plateau in Champasak province in south-western Lao PDR is reported. The moth, which is native to South America, has invaded many countries in Europe, Africa, and Asia since 2006, and, based on regional records possibly entered Lao PDR between 2014 and 2018. It is a devastating pest of solanaceous crops and threatens tomato production worldwide. Further surveys are required to determine its presence in other regions of Lao PDR and effective management programs must be developed to help farmers minimise losses.

Introduction Physicians play a critical role in encouraging their patients to get vaccinated, in part by responding to patients’ concerns about vaccines. It is, therefore, important to understand what difficulties physicians have in dealing with different concerns they may encounter. The aim of this article was to determine physicians’ perceptions of difficulties in rebutting different antivaccination arguments from patients using data collected as part of a cross-sectional, cross-national questionnaire on physicians’ vaccine attitudes and behaviours.Methods Physicians in 4 European countries (Finland, Germany, France and Portugal, total n=2718) rated 33 different arguments, chosen to represent 11 different psychological motivations underlying vaccine hesitancy, in terms of their perceptions of how difficult each argument would be to rebut.Results Across all countries, physicians perceived arguments based on religious concerns and ‘reactance’ (ie, resistance to perceived curbs of freedom) to be the most difficult to rebut, whereas arguments based on patients’ distorted perception of the risks of disease and vaccines were perceived to be the easiest. There were also between-country differences in the level of perceived difficulty of argument rebuttal. Physicians’ perceived difficulty with rebutting arguments was significantly negatively correlated with their vaccine recommendation behaviours and their preparedness for vaccination discussions.Conclusions Physicians may feel better equipped to counter arguments that can be rebutted with facts and evidence but may struggle to respond when arguments are motivated by psychological dispositions or values.

Abstract Every animal secretes mucus, placing them among the most diverse biological materials. Mucus hydrogels are complex mixtures of water, ions, carbohydrates, and proteins. Uncertainty surrounding their composition and how interactions between components contribute to mucus function complicates efforts to exploit their properties. There is substantial interest in commercializing mucus from the garden snail, Cornu aspersum, for skincare, drug delivery, tissue engineering, and composite materials. C. aspersum secretes three mucus—one shielding the animal from environmental threats, one adhesive mucus from the pedal surface of the foot, and another pedal mucus that is lubricating. It remains a mystery how compositional differences account for their substantially different properties. Here, we characterize mucus proteins, glycosylation, ion content, and mechanical properties that could be used to provide insight into structure-function relationships through an integrative “mucomics” approach. We identify macromolecular components of these hydrogels, including a previously unreported protein class termed Conserved Anterior Mollusk Proteins (CAMPs). Revealing differences between C. aspersum mucus shows how considering structure at all levels can inform the design of mucus-inspired materials.

Citrus virus A (CiVA) was detected for the first time in Australia in a living pathogen collection. Buds were originally collected from a Washington navel field tree prior to 1970 and graft-inoculated onto a Symons sweet orange indicator plant. The virus was detected using conventional and quantitative reverse transcription polymerase chain reactions and high-throughput sequencing. This variant shares 96.3% (RNA1) and 96.7% (RNA2) nucleotide identity with isolates of CiVA from South Africa and China, respectively. Foliar symptoms of leaf flecking and oak leaf patterns, consistent with detections of CiVA in other regions, were observed on the foliage of the original accession and inoculated indicator plants. Subsequent surveys of an Australian citrus variety collection detected a different CiVA sequence variant in two accessions of Pera sweet orange; this variant had 97% similarity to the other Australian variant.

Citrus has been promoted in the Lao People’s Democratic Republic (Lao PDR) as a poverty reduction strategy for at least two decades. However, citrus trees have been in widespread decline for no less than ten years. Since 2010, the authors have observed symptoms on citrus trees consistent with the bacterial disease huanglongbing (HLB). These symptoms included asymmetric leaf mottle, small lopsided fruit, poor fruit production and tree decline. The authors then initiated a long-term study on the occurrence of HLB in southern Lao PDR. Samples of leaf mid-ribs were collected from citrus trees in orchards, nurseries, and backyards across four provinces: Champasak, Sekong, Salavan, and Savannakhet. The presence of ‘Candidatus Liberibacter asiaticus’, the putative causal agent of the Asiatic form of HLB, was confirmed in 59 of 109 samples collected in all four provinces. The Asian citrus psyllid, the vector of ‘Ca. L. asiaticus’, was also observed on citrus trees and tested positive for the pathogen. The implications of these findings for citrus production in Lao PDR are discussed.

Two points arising from Isaac Nowell's review of Sally Coulthard's The Apple (September 20). Long before Milton, the fruit that brought about the Fall had been identified as an apple [...]

Abstract The proliferation of anti-vaccination arguments online can threaten immunisation programmes, including those targeting COVID-19. To effectively refute misinformed views about vaccination, communicators need to go beyond providing correct information and debunking of misconceptions, and must consider the underlying motivations of people who hold contrarian views. Drawing on a taxonomy of anti-vaccination arguments that identified 11 “attitude roots”—i.e., psychological attributes—that motivate an individual’s vaccine-hesitant attitude, we assessed whether these attitude roots were identifiable in argument endorsements and responses to psychological construct measures corresponding to the presumed attitude roots. In two UK samples (total n = 1250), we found that participants exhibited monological belief patterns in their highly correlated endorsements of anti-vaccination arguments drawn from different attitude roots, and that psychological constructs representing the attitude roots significantly predicted argument endorsement strength and vaccine hesitancy. We identified four different latent anti-vaccination profiles amongst our participants’ responses. We conclude that endorsement of anti-vaccination arguments meaningfully dovetails with attitude roots clustering around anti-scientific beliefs and partisan ideologies, but that the balance between those attitudes differs considerably between people. Communicators must be aware of those individual differences.