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Background Despite disproportionate rates of mental ill-health compared with non-Indigenous populations, few programs have been tailored to the unique health, social, and cultural needs and preferences of young Aboriginal and Torres Strait Islander males. This paper describes the process of culturally adapting the US-based Young Black Men, Masculinities, and Mental Health (YBMen) Project to suit the needs, preferences, culture, and circumstances of Aboriginal and Torres Strait Islander males aged 16–25 years in the Northern Territory, Australia. YBMen is an evidence-based social media-based education and support program designed to promote mental health, expand understandings of gender and cultural identities, and enhance social support in college-aged Black men. Methods Our adaptation followed an Extended Stages of Cultural Adaptation model. First, we established a rationale for adaptation that included assessing the appropriateness of YBMen’s core components for the target population. We then investigated important and appropriate models to underpin the adapted program and conducted a non-linear, iterative process of gathering information from key sources, including young Aboriginal and Torres Strait Islander males, to inform program curriculum and delivery. Results To maintain program fidelity, we retained the core curriculum components of mental health, healthy masculinities, and social connection and kept the small cohort, private social media group delivery but developed two models: ‘online only’ (the original online delivery format) and ‘hybrid in-person/online’ (combining online delivery with weekly in-person group sessions). Adaptations made included using an overarching Aboriginal and Torres Strait Islander social and emotional wellbeing framework and socio-cultural strengths-based approach; inclusion of modules on health and wellbeing, positive Indigenous masculinities, and respectful relationships; use of Indigenous designs and colours; and prominent placement of images of Aboriginal and Torres Strait Islander male sportspeople, musicians, activists, and local role models. Conclusions This process resulted in a culturally responsive mental health, masculinities, and social support health promotion program for young Aboriginal and Torres Strait Islander males. Next steps will involve pilot testing to investigate the adapted program’s acceptability and feasibility and inform further refinement. Keywords: Aboriginal, Torres Strait Islander, Indigenous, Australia, male, cultural adaptation, social media, mental health, masculinities, social support.

Abstract Introduction There is currently a lack of research regarding disease course and burden as well as treatment patterns and goals in patients with non-segmental vitiligo (NSV). The aim of this analysis was to evaluate disease course, treatment patterns and goals in patients with NSV. Methods This analysis used secondary data from the Adelphi Real World Vitiligo Disease Specific Programme™ 2021, specifically, a survey of physicians and their adult and adolescent patients with NSV. Physicians categorized patients by the extent of NSV at time of survey completion as mild, moderate or severe/very severe. Physician-reported patient information included demographics, current/previously prescribed NSV therapies, treatment satisfaction and the Vitiligo Noticeability Scale (VNS). Patients completed a survey on treatment satisfaction and the VNS. Treatment pattern data were stratified by disease extent and Fitzpatrick skin type. Results At survey completion, physicians reported that 38, 50 and 12% of patients (N = 1865) had improving, stable and deteriorating/progressing disease, respectively. Most patients (96%) with mild disease at treatment initiation still had mild disease at the time of survey completion. More than half of patients with moderate disease (62%) or severe/very severe disease (57%) at treatment initiation still had moderate or severe/very severe disease at survey completion. Topical calcineurin inhibitors (TCIs) were the most common treatment in 40% of patients followed by phototherapy in 30%. Patients hoped for re-pigmentation (mild 56%, moderate 62%, severe/very severe 66%), reduction (mild 50%, moderate 56%, severe/very severe 49%) or cessation of affected areas with vitiligo (mild 48%, moderate 54%, severe/very severe 43%). Conclusion The study findings indicate that a significant proportion of patients with NSV are not improving on current treatments, most commonly TCIs and phototherapy. The results highlight the unmet need for novel and effective therapies to substantially improve re-pigmentation, an important treatment goal for patients with NSV.

Abstract Introduction Vitiligo was historically regarded as a cosmetic disorder; however, it is an autoimmune disease. As a visible condition, it affects patient well-being. We assessed the impact of disease severity, lesion location, and body surface area (BSA) affected on patient health-related quality of life (HRQoL). Methods Retrospective data were from the Adelphi Real World Vitiligo Disease Specific Programme: a cross-sectional survey of physicians and their patients with vitiligo (10/2021–07/2022). Patient-reported outcomes were assessed by the Vitiligo-Specific Quality of Life Instrument (VitiQoL), Hospital Anxiety and Depression Scale (HADS), and EQ-5D-5L. The Work Productivity and Impairment Questionnaire (WPAI) questionnaire was used to assess disease-related impairment of daily activities. Data were stratified by physician-reported disease severity, presence/absence of vitiligo on the face, and BSA percentage affected. Results In total, 1388 patients were included. Mean (SD) VitiQoL, HADS depression, and anxiety scores were higher for those with severe disease [40.5 (26.1), 5.2 (4.4), and 6.8 (4.7)] than those with mild [24.8 (18.8), 3.6 (3.8), 4.2 (3.8)] or moderate [27.1 (22.6), 3.8 (4.5), 4.3 (4.4)] disease. Patients with face affected reported higher VitiQoL [30.0 (22.3) versus 23.2 (19.3)], and HADS scores [depression, 4.3 (4.3) versus 3.2 (3.9); anxiety, 5.0 (4.3) versus 3.8 (3.9)] than those without. Patients with ≥ 5% BSA affected had higher VitiQoL, depression and anxiety scores [27.9 (21.8), 4.0 (4.4), and 4.5 (4.2)] than those with 0–5% [24.6 (19.7), 3.4 (3.7), and 4.3 (4.1)]. Patients with severe vitiligo, facial lesions, or ≥ 5% BSA reported higher activity impairment. Mean EQ-5D-5L-utility score was approximately 0.9 regardless of disease severity or total BSA affected. Conclusions These data demonstrate the impact disease severity can have on HRQoL and daily activities for patients with vitiligo. Lesions that are more severe, on the face, or covering a greater BSA are more often associated with poorer outcomes and activity impairment. These data also highlight the potential insensitivity of commonly used HRQoL measures and a need for more sensitive disease-specific measures.

Abstract Introduction Vitiligo is a chronic autoimmune disease characterized by destruction of melanocytes, leading to skin depigmentation. Vitiligo can have a high quality-of-life burden and profound impact on psychosocial well-being. The objectives of this study were to describe the self-reported patient burden among patients with nonsegmental vitiligo with ≤ 10% affected body surface area, summarize the physician-reported psychosocial and psychological impact of vitiligo on patient lives, and describe disease characteristics and treatment history, goals, and satisfaction. Methods Data were drawn from the Adelphi Vitiligo Disease Specific Programme™, a real-world, cross-sectional survey with retrospective data collection of physicians and patients with vitiligo, collected in the United States between October 2021 and April 2022. Separate surveys for dermatologists and patients contained questions on clinical and demographic characteristics of patients with vitiligo and burden of vitiligo. Treatment history, goals, and satisfaction were assessed together with the impact of vitiligo on quality of life. Results Sixty-one dermatologists provided data for 326 patients with ≤ 10% affected body surface area (adults, n = 221; adolescents, n = 105); 90 of those patients also responded to the survey. The most common treatments were topical corticosteroids, topical calcineurin inhibitors, and narrow-band ultraviolet-B phototherapy, with the main treatment goal being repigmentation. Physician-reported treatment satisfaction was 56%; 25% of patients reported frustration with treatment options. Physicians reported impact of vitiligo on everyday life in 46% of patients. Patients reported 12.7% overall work impairment; mean scores for Hospital Anxiety and Depression Scale anxiety and depression domains were 3.5 and 2.2, respectively, and mean Vitiligo-specific Quality of Life index score was 26.9. Patients with facial involvement experienced higher burden than those without. Conclusion A high patient burden was reported by dermatologists and their patients with vitiligo who had ≤ 10% affected body surface area, including psychosocial and psychological consequences. These findings highlight an unmet need in the treatment of vitiligo.

During decision-making, animals may use either innate or plastic behaviours. This has been suggested to be important for generalist phytophagous insects where females need to assess a large range of cues during host plant selection for oviposition. To facilitate the choice, generalists may thus use innate preference hierarchies among host plants combined with phenotypic plasticity based on earlier host experience, but if populations differ in whether they rely on innate or plastic factors during decision-making is not well-known. Females from an Egyptian population of the polyphagous moth Spodoptera littoralis has previously been found to shift preference between plants in their innate preference hierarchy depending on larval host plant experience. We studied the innate preference hierarchy for three host plants (cotton, cabbage and cowpea), and whether the hierarchy shifts based on larval host plant experience, in a Northern range margin population (Italy) and a core population (Kenya) of S. littoralis, to see if and how these traits vary across populations. In addition, we studied larval performance on the three host plants in all three populations. The Italian and Kenyan populations had different innate preference hierarchies, and both hierarchies differed from the hierarchy that has previously been found in the Egyptian population. Furthermore, the host plant selection of ovipositing females was affected by larval diet in the Italian and Kenyan population, but the larval host plant experience did not completely shift the preference hierarchy as in the Egyptian population. This indicates that not only host plant preference per se, but also phenotypic plasticity during host plant selection can vary between populations. We further found that the populations responded differently to larval diet for some performance traits. However, it was only the Italian population that showed indications of any link between preference and performance, as they had slower development on their least preferred host plant. Overall, preference divergence between populations seems not to be driven by local variation in larval performance.

Abstract Introduction The 2021 US approval of ruxolitinib cream for treatment of atopic dermatitis (AD) in patients aged ≥ 12 years was based on the results of two pivotal phase 3 studies. Currently, real-world data to describe effectiveness of ruxolitinib cream and physician satisfaction with treatment remain limited. Our objective is to describe disease control among adults with mild to moderate AD prescribed ruxolitinib cream and physician satisfaction with treatment. Methods Data were from the Adelphi AD Disease Specific Programme™, a US real-world, cross-sectional survey of physician-reported data, undertaken between August 2022 and March 2023. For patients aged ≥ 18 years, physicians reported patient demographics, clinical characteristics, treatment patterns, and physician satisfaction with disease control. Descriptive analysis of data for patients with mild to moderate AD prior to the initiation of ruxolitinib cream and treated with ruxolitinib cream for ≥ 1 month was undertaken. Results Among physician-reported data from 1360 patients with AD, 149 patients had received ruxolitinib cream (in combination or as monotherapy) for ≥ 1 month, including 59 patients receiving monotherapy. Prior to treatment with ruxolitinib cream, 84.6% of patients had moderate AD (Investigator’s Global Assessment, IGA of 3), whereas after treatment (median duration, 26 weeks), only 21.5% had an IGA of 3, with 48.3% of patients having clear or almost clear skin (IGA of 0/1). For these patients, 81.2% were not currently experiencing a flare, and physicians were satisfied with disease control for 87.3%. Results were similar in patients receiving monotherapy. The most frequent physician-reported reasons for prescribing ruxolitinib cream included relieving itch, improving lesion redness/thickness, achieving disease control, and reducing/controlling flares. Conclusions These real-world findings demonstrate effective disease control and physician satisfaction with ruxolitinib cream for the treatment of AD in adults in a clinical practice setting. Outcomes were similar whether ruxolitinib cream was prescribed as monotherapy or in combination regimens, suggesting a role for ruxolitinib cream across the spectrum of disease.

Abstract In the Americas, the fall armyworm (Spodoptera frugiperda) exists in two genetically distinct strains, the corn (C) and rice (R) strains. Despite their names, these strains are not associated with host plant preferences but have been shown to vary in pheromone composition and male responses. Recently, S. frugiperda was detected in Africa as an invasive species, but knowledge about variation in strain types, pheromone composition and inter-strain mating of populations of the pest in the continent has not been fully examined. Therefore, this study aimed to investigate variations, if any in the pheromone composition of female moths, male moth responses, and mating between C and R mitotypes of S. frugiperda populations in Kenya, as well as their geographic distribution. Strains (mitotypes) of S. frugiperda were identified using mitochondrial DNA (mtDNA) markers, and their pheromonal composition determined by coupled gas chromatography–mass spectrometric (GC–MS) analysis. Male moth responses to these compounds were evaluated using GC-electroantennographic detection (EAD), electroantennogram (EAG), and wind tunnel assays. Oviposition assays were used to determine whether R and C mitotype moths could mate and produce eggs. The results showed that both the R and C mitotypes were present, and there were no statistically significant differences in their distribution across all sampled locations. Five pheromone compounds including (Z)-7-dodecenyl acetate (Z7-12:OAc), (Z)-7-tetradecenyl acetate (Z7-14:OAc), (Z)-9-tetradecenyl acetate (Z9-14:OAc), (Z)-11-tetradecenyl acetate (Z11-14:OAc) and (Z)-11-hexadecenyl acetate (Z11-16:OAc), were detected in the pheromone glands of female moths of both mitotypes, with Z9-14:OAc being the most abundant. The relative percentage composition of Z9-14:OAc was similar in both mitotypes. However, the R mitotype had a 2.7 times higher relative percentage composition of Z7-12:OAc compared to the C mitotype moth, while the C mitotype moth had a 2.4 times higher relative percentage composition of Z11-16:OAc than the R mitotype moth. Male moths of both mitotypes exhibited similar responses to the pheromone compounds, showing the strongest responses to Z9-14:OAc and Z7-12:OAc in electrophysiological and behavioural assays. There was mating between R and C mitotypes with egg production comparable to mating within the same mitotype. Our results revealed that differences between the two S. frugiperda mitotypes are characterized by female moth pheromone composition rather than male moth responses to the pheromones, and that this does not prevent hybridisation between the mitotypes, which may have implications for their management.

This review updates the present status of the field of molecular markers and marker-assisted selection (MAS), using the example of drought tolerance in barley. The accuracy of selected quantitative trait loci (QTLs), candidate genes and suggested markers was assessed in the barley genome cv. Morex. Six common strategies are described for molecular marker development, candidate gene identification and verification, and their possible applications in MAS to improve the grain yield and yield components in barley under drought stress. These strategies are based on the following five principles: (1) Molecular markers are designated as genomic ‘tags’, and their ‘prediction’ is strongly dependent on their distance from a candidate gene on genetic or physical maps; (2) plants react differently under favourable and stressful conditions or depending on their stage of development; (3) each candidate gene must be verified by confirming its expression in the relevant conditions, e.g., drought; (4) the molecular marker identified must be validated for MAS for tolerance to drought stress and improved grain yield; and (5) the small number of molecular markers realized for MAS in breeding, from among the many studies targeting candidate genes, can be explained by the complex nature of drought stress, and multiple stress-responsive genes in each barley genotype that are expressed differentially depending on many other factors.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Chickpea (Cicer arietinum L.) is a very important food legume and needs improved drought tolerance for higher seed production in dry environments. The aim of this study was to determine diversity and genetic polymorphism in zinc finger knuckle genes with CCHC domains and their functional analysis for practical improvement of chickpea breeding. Two CaZF-CCHC genes, Ca04468 and Ca07571, were identified as potentially important candidates associated with plant responses to drought and dehydration. To study these genes, various methods were used including Sanger sequencing, DArT (Diversity array technology) and molecular markers for plant genotyping, gene expression analysis using RT-qPCR, and associations with seed-related traits in chickpea plants grown in field trials. These genes were studied for genetic polymorphism among a set of chickpea accessions, and one SNP was selected for further study from four identified SNPs between the promoter regions of each of the two genes. Molecular markers were developed for the SNP and verified using the ASQ and CAPS methods. Genotyping of parents and selected breeding lines from two hybrid populations, and SNP positions on chromosomes with haplotype identification, were confirmed using DArT microarray analysis. Differential expression profiles were identified in the parents and the hybrid populations under gradual drought and rapid dehydration. The SNP-based genotypes were differentially associated with seed weight per plant but not with 100 seed weight. The two developed and verified SNP molecular markers for both genes, Ca04468 and Ca07571, respectively, could be used for marker-assisted selection in novel chickpea cultivars with improved tolerance to drought and dehydration.

Background The ability to cope with concussion symptoms and manage stress is an important determinant of risk for prolonged symptoms. Objective This open-label mixed-methods pilot study assessed the acceptability and credibility of a mindfulness-based intervention delivered through a digital therapeutic (DTx; therapeutic smartphone app) for pediatric concussion. Methods Participants aged 12 to 18 years were recruited from an emergency department within 48 hours of a concussion (acute cohort) or from a tertiary care clinic at least 1-month post-concussion (persisting symptoms cohort). Participants completed a novel 4-week mindfulness-based intervention, for 10 to 15 minutes/day, at a minimum of 4 days/week. At 2 weeks, participants completed a credibility and expectancy questionnaire. At 4 weeks, participants completed questionnaires assessing satisfaction, usability and working alliance, as well as a semi-structured phone interview. Results Ten participants completed the study outcomes (7 acute; 3 persisting symptoms). The intervention was perceived as credible (median/max possible = 6.50/9.00 [6.83,8.75]) and DTx was usable (median/max possible = 70.00/100.00 [55.00,82.50]). Participants rated their satisfaction with the DTx (median/max possible = 27.00/32.00 [24.50,29.50]) and the working alliance with the digital mindfulness guides (median/max possible = 3.92/5.00 [3.38–4.33]) as high. Four themes were identified from the qualitative data: (a) positive attributes; (b) negative attributes; (c) ideas for modifications; and (d) technical issues. Conclusion Results show modifications to the DTx, instructions and mindfulness intervention, and potential ways to increase adherence by leveraging positive attributes. A randomized control trial will assess the effectiveness of the DTx MBI to decrease the risk of persisting symptoms and reduce the symptom burden following pediatric concussion.

Abstract Introduction Alopecia areata (AA) is characterized by non-scarring scalp and/or body hair loss and can negatively impact patient mental health. Data are limited on the alignment of patient and physician perceptions of AA severity with each other and with Japanese Dermatological Association (JDA) guideline criteria, and of patient-physician alignment on treatment satisfaction. Therefore, we performed analyses to compare JDA severity groupings with patient-physician alignment on disease severity and to explore treatment satisfaction in AA in Japan. Methods Data were drawn from the Adelphi AA Disease Specific Programme (DSP)™, a real-world survey of physicians and patients with AA in Japan conducted January-March 2021. Patients and physicians reported patient AA severity as mild, moderate or severe based on their subjective judgement. Patients were then categorized into five hair loss severity groups according to JDA criteria (S1-5), and patient-physician pairs were matched to assess alignment on severity and treatment satisfaction. Results Subjective patient- and physician-reported disease severity generally followed JDA severity groupings. The percentage of patient-physician alignment on severity recognition was 76.3% in the overall population. In misaligned pairs, 20.2%, 14.5%, 7.3%, 25.0% and 0.0% of physicians rated disease as more severe than patients in S1, S2, S3, S4 and S5, respectively. Regarding treatment satisfaction, patient-physician alignment was 57.6% in the overall population. In S5, 46.2% of physicians reported being less satisfied than patients. Both physicians and patients cited lack of efficacy as the main reason for dissatisfaction. Of 221 patients, 39.8% and 29.9% were categorized as borderline-abnormal cases for anxiety and depression, respectively. Conclusions This study highlights previously unreported patient-physician misalignment on disease severity, level of treatment dissatisfaction and unmet needs due to the lack of effective treatment. Further study on how improvement of the misalignment between physicians and patients could increase both patient and physician satisfaction with treatment and improve the quality of life for patients with AA.

Salinity tolerance was studied in chickpea accessions from a germplasm collection and in cultivars from Kazakhstan. After NaCl treatment, significant differences were found between genotypes, which could be arranged into three groups. Those that performed poorest were found in group 1, comprising five ICC accessions with the lowest chlorophyll content, the highest leaf necrosis (LN), Na+ accumulation, malondialdehyde (MDA) content, and a low glutathione ratio GSH/GSSG. Two cultivars, Privo-1 and Tassay, representing group 2, were moderate in these traits, while the best performance was for group 3, containing two other cultivars, Krasnokutsky-123 and Looch, which were found to have mostly green plants and an exact opposite pattern of traits. Marker–trait association (MTA) between 6K DArT markers and four traits (LN, Na+, MDA, and GSH/GSSG) revealed the presence of four possible candidate genes in the chickpea genome that may be associated with the three groups. One gene, ATP-binding cassette, CaABCC6, was selected, and three haplotypes, A, D1, and D2, were identified in plants from the three groups. Two of the most salt-tolerant cultivars from group 3 were found to have haplotype D2 with a novel identified SNP. RT-qPCR analysis confirmed that this gene was strongly expressed after NaCl treatment in the parental- and breeding-line plants of haplotype D2. Mass spectrometry of seed proteins showed a higher accumulation of glutathione reductase and S-transferase, but not peroxidase, in the D2 haplotype. In conclusion, the CaABCC6 gene was hypothesized to be associated with a better response to oxidative stress via glutathione metabolism, while other candidate genes are likely involved in the control of chlorophyll content and Na+ accumulation.

We used the 2005–2010 National Health and Nutrition Examination Survey (NHANES), constructed to evaluate health of adults in the United States using consolidated data from interviews and physical exams that were conducted to obtain data for this study. The analysis sample was representative of noninstitutionalized US adults aged 20–59 years. When considering sexual frequency, overall, only female participants with lower sexual frequency were at a higher risk of all-cause death in a dose-response manner with a hazard ratio (HR) of 1.70 (95% CI 1.38–2.10, p trend < .001) during the follow-up period. This relationship was not significant in males. However, when sexual frequency was categorized (

The issue of how to best address Indigenous education needs has long been a public debate. There has been much discussion in the educational system, at policy levels and at universities. However, little is known about the perception of Indigenous peoples in regard to the education that their children are receiving or how to incorporate their traditional knowledge inside the classroom. This paper shares such a study and explores the views of Indigenous people living in rural communities of the Atacama Desert of Chile. Views are shared about the needs of their children and that of teacher education. Using a decolonising rights-based methodology, the study aimed to highlight the voices of Atacameños people, who talked about their relationship with schoolteachers, their role in supporting schools and the role of the traditional educator. Findings suggest that even though Indigenous community members perceived their engagement as key in incorporating local knowledge inside the classroom, they realised they are not actively participating in school organisation. There is also a perception that the role of the traditional educator needs to be valued more because they are crucial for reducing the gap between the Indigenous community and local schools.

Objetivo. Medir el efecto de la pandemia de COVID-19 en la implementación de un programa de detección oportuna, intervención breve y referencia para tratamiento por consumo de alcohol en centros de salud del primer nivel de atención de la Ciudad de México. Métodos. Se recopilaron los datos en 18 centros de salud de la Ciudad de México entre 2019 y 2021, como parte de un estudio más amplio. Participaron 287 profesionales de la salud, quienes midieron el consumo de alcohol de sus pacientes con la prueba AUDIT-C. Se analizaron aspectos demográficos y patrones de consumo de los pacientes, así como las acciones de atención (detección, intervención breve, entrega de folletos, monitoreo y referencia) en tres momentos: antes de la pandemia de COVID-19, durante el confinamiento y luego del confinamiento. Se realizaron pruebas paramétricas y no paramétricas para identificar la relación y las diferencias entre las variables en los tres períodos. Resultados. Se identificaron 9090 personas con consumo de alcohol; el porcentaje de detección del consumo tuvo fluctuaciones en los tres períodos estudiados (26%, 53% y 37%, respectivamente). El consumo de riesgo medio y alto fue más frecuente entre hombres jóvenes y con mayor escolaridad durante y después del confinamiento. En el período posconfinamiento aumentaron las acciones de monitoreo y referencia. Conclusiones. La medición del impacto de la pandemia en la implementación de un programa de detección oportuna, asesoramiento breve y referencia para el tratamiento del consumo de alcohol en centros de salud ayuda a elaborar políticas en salud por edad, género, escolaridad y tipo de consumo para el primer nivel de atención.

Traditionally, adult and neonatal cerebral perfusion have been presumed to be symmetrical. Contrary to this, our adult work shows that supra-aortic cerebral supply is systematically biased towards the left, in terms of both vessel geometry and blood flow volumes. Although this asymmetry is meaningfully related to hand preference, the developmental origins of this association remain unknown. Our detailed investigations of the cerebral vasculature confirm analogous asymmetries in term neonates. Specifically, we demonstrate that the structure and flow of neonatal middle cerebral vessels are consistently asymmetric and predominantly left-dominant. Building on our work from the same cohort, we now report further analyses of these new-found asymmetries. Namely, exploring for the first time, the relationship between arterial lateral biases and the neonatal head-turning response—a reliable early behavioural precursor of handedness that shows a systematic rightward bias in the population. Here, we demonstrate a contralateral relationship between vessel morphology and primitive expressions of lateralisation that predate the establishment of definitive handedness in the course of postnatal development. This relationship mimics patterns observed in adults and suggests that lateralising trends in angiogenesis may ultimately influence the emergence of human lateral preferences.

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

Summary: Background: It is unclear if expiratory airflow in survivors born extremely low birth weight (ELBW; 500–999 g) has improved after the introduction of exogenous surfactant into clinical practice in 1991. The primary aim of this study was to describe the changes in airflow at 7–8 years of age of survivors born ELBW in five discrete cohorts from 14 years before to 14 years after the introduction of exogenous surfactant into clinical practice. Methods: The cohorts comprised consecutive survivors born ELBW in 1977–82 and 1985–87 at the Royal Women's Hospital, Melbourne, and in 1991–92, 1997 and 2005 in the state of Victoria, Australia. Survival rates to 2-years of age for infants born ELBW in the state of Victoria rose from approximately 1-in-4 to 3-in-4 over the time of this study. Expiratory airflow measurements at 7–8 years included the forced expired volume in 1 s (FEV1), converted to z-scores for age, height, sex, and race. Findings: There were 596 ELBW participants with expiratory flow data, 280 (47%) of whom had bronchopulmonary dysplasia (BPD). Overall, there was little change in zFEV1 over the 28-year period (mean change per year; 0.003, 95% CI −0.010, 0.015, P = 0.67). There was, however, evidence of an interaction between BPD and year; zFEV1 in those who had BPD fell over time (mean change per year −0.019, 95% CI −0.037, −0.009, P = 0.035), whereas zFEV1 improved in those who did not have BPD (mean change per year 0.021, 95% CI 0.006, 0.037, P = 0.007). Interpretation: Contrary to recent evidence, expiratory airflow of children born ELBW has not improved with the introduction of surfactant, and may be deteriorating in those who had BPD. Funding: National Health and Medical Research Council (Australia); Victorian Government’s Operational Infrastructure Support Program.

Diet composition is vital in shaping gut microbial assemblage in many insects. Minimal knowledge is available about the influence of transgenerational diet transition on gut microbial community structure and function in polyphagous pests. This study investigated transgenerational diet-induced changes in Spodoptera littoralis larval gut bacteriome using 16S ribosomal sequencing. Our data revealed that 88% of bacterial populations in the S. littoralis larval gut comprise Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. The first diet transition experiment from an artificial diet (F0) to a plant diet (F1), cabbage and cotton, caused an alteration of bacterial communities in the S. littoralis larval gut. The second transgenerational diet switch, where F1 larvae feed on the same plant in the F2 generation, displayed a significant variation suggesting further restructuring of the microbial communities in the Spodoptera larval gut. F1 larvae were also challenged with the plant diet transition at the F2 generation (cabbage to cotton or cotton to cabbage). After feeding on different plant diets, the microbial assemblage of F2 larvae pointed to considerable differences from other F2 larvae that continued on the same diet. Our results showed that S. littoralis larval gut bacteriome responds rapidly and inexplicably to different diet changes. Further experiments must be conducted to determine the developmental and ecological consequences of such changes. Nevertheless, this study improves our perception of the impact of transgenerational diet switches on the resident gut bacteriome in S. littoralis larvae and could facilitate future research to understand the importance of symbiosis in lepidopteran generalists better.

Summary: Unlike mammals, most invertebrates provide no direct parental care for their progeny, which makes a well-selected oviposition site crucial. However, little is known about the female evaluation of opportunities and threats during host selection. Leveraging the wide range of host plants used by the polyphagous pest, Spodoptera littoralis, we investigate oviposition choice between two plants of different nutritional quality. Females prefer to lay their eggs on the host plant, which has inferior larval development and more natural enemies but provides lower predation rates. On the superior host plant, a major predator shows more successful search behavior and is more attracted to herbivore-induced volatiles. Our findings show that predator efficacy and odor-guided attraction, rather than predator abundance, determine enemy free space. We postulate that predators' behaviors contribute to the weak correlation between preference and performance during host plant selection in S. littoralis and in polyphagous insects in general.

Researchers and practitioners recognise the importance of context when implementing healthcare interventions, but the influence of wider environment is rarely mapped. This paper identifies the country and policy-related factors potentially explaining the country differences in outcomes of an intervention focused on improving detection and management of heavy alcohol use in primary care in Colombia, Mexico and Peru. Qualitative data obtained through interviews, logbooks and document analysis are used to explain quantitative data on number of alcohol screenings and screening providers in each of the countries. Existing alcohol screening standards in Mexico, and policy prioritisation of primary care and consideration of alcohol as a public health issue in Colombia and Mexico positively contributed to the outcome, while the COVID-19 pandemic had a negative impact. In Peru, the context was unsupportive due to a combination of: political instability amongst regional health authorities; lack of focus on strengthening primary care due to the expansion of community mental health centres; alcohol considered as an addiction rather than a public health issue; and the impact of COVID-19 on healthcare. We found that wider environment-related factors interacted with the intervention implemented and can help explain country differences in outcomes.

Abstract Background The detection of environmental cues and signals via the sensory system directs behavioral choices in diverse organisms. Insect larvae rely on input from the chemosensory system, mainly olfaction, for locating food sources. In several lepidopteran species, foraging behavior and food preferences change across larval instars; however, the molecular mechanisms underlying such behavioral plasticity during larval development are not fully understood. Here, we hypothesize that expression patterns of odorant receptors (ORs) change during development, as a possible mechanism influencing instar-specific olfactory-guided behavior and food preferences. Results We investigated the expression patterns of ORs in larvae of the cotton leafworm Spodoptera littoralis between the first and fourth instar and revealed that some of the ORs show instar-specific expression. We functionally characterized one OR expressed in the first instar, SlitOR40, as responding to the plant volatile, β-caryophyllene and its isomer α-humulene. In agreement with the proposed hypothesis, we showed that first but not fourth instar larvae responded behaviorally to β-caryophyllene and α-humulene. Moreover, knocking out this odorant receptor via CRISPR-Cas9, we confirmed that instar-specific responses towards its cognate ligands rely on the expression of SlitOR40. Conclusion Our results provide evidence that larvae of S. littoralis change their peripheral olfactory system during development. Furthermore, our data demonstrate an unprecedented instar-specific behavioral plasticity mediated by an OR, and knocking out this OR disrupts larval behavioral plasticity. The ecological relevance of such behavioral plasticity for S. littoralis remains to be elucidated, but our results demonstrate an olfactory mechanism underlying this plasticity in foraging behavior during larval development.

Background Effective interventions exist for heavy drinking and depression but to date there has been limited translation into routine practice in global health systems. This evidence-to-practice gap is particularly evident in low- and middle-income countries. The international SCALA project (Scale-up of Prevention and Management of Alcohol Use Disorders and Comorbid Depression in Latin America) sought to test the impact of multilevel implementation strategies on rates of primary health care-based measurement of alcohol consumption and identification of depression in Colombia, Mexico, and Peru. Objective To describe the process of development and cultural adaptation of the clinical intervention and training package. Methods We drew on Barrero and Castro’s four-stage cultural adaption model: 1) information gathering, 2) preliminary adaption, 3) preliminary adaption tests, and 4) adaption refinement. The Tailored Implementation in Chronic Diseases checklist helped us identify potential factors that could affect implementation, with local stakeholder groups established to support the tailoring process, as per the Institute for Healthcare Improvement’s Going to Scale Framework. Results In Stage 1, international best practice guidelines for preventing heavy drinking and depression, and intelligence on the local implementation context, were synthesised to provide an outline clinical intervention and training package. In Stage 2, feedback was gathered from local stakeholders and materials refined accordingly. These materials were piloted with local trainers in Stage 3, leading to further refinements including developing additional tools to support delivery in busy primary care settings. Stage 4 comprised further adaptions in response to real-world implementation, a period that coincided with the onset of the COVID-19 pandemic, including translating the intervention and training package for online delivery, and higher priority for depression screening in the clinical pathway. Conclusion Our experience highlights the importance of meaningful engagement with local communities, alongside the need for continuous tailoring and adaptation, and collaborative decision-making.

Height from soil at the base of plant to the first pod (HFP) is an important trait for mechanical harvesting of legume crops. To minimise the loss of pods, the HFP must be higher than that of the blades of most combine harvesters. Here, we review the genetic control, morphology, and variability of HFP in legumes and attempt to unravel the diverse terminology for this trait in the literature. HFP is directly related to node number and internode length but through different mechanisms. The phenotypic diversity and heritability of HFP and their correlations with plant height are very high among studied legumes. Only a few publications describe a QTL analysis where candidate genes for HFP with confirmed gene expression have been mapped. They include major QTLs with eight candidate genes for HFP, which are involved in auxin transport and signal transduction in soybean [Glycine max (L.) Merr.] as well as MADS box gene SOC1 in Medicago trancatula, and BEBT or WD40 genes located nearby in the mapped QTL in common bean (Phaseolus vulgaris L.). There is no information available about simple and efficient markers associated with HFP, which can be used for marker-assisted selection for this trait in practical breeding, which is still required in the nearest future. To our best knowledge, this is the first review to focus on this significant challenge in legume-based cropping systems.

Objective To assess the immediate impact of the introduction of minimum unit pricing (MUP) in Scotland on alcohol consumption and whether the impact differed by sex, level of alcohol consumption, age, social grade and level of residential deprivation of respondents.Design Primary controlled interrupted time series analysis and secondary before-and-after analysis of the impact of introducing MUP in Scotland using alcohol consumption data for England as control.Setting Data from Kantar Worldpanel’s Alcovision survey, a continuous retrospective online timeline follow-back diary survey of the previous week’s alcohol consumption.Participants 53 347 women and 53 143 men.Interventions Introduction of a minimum price of 50 pence per UK unit (6.25 pence/g) for the sale of alcohol in Scotland on 1 May 2018.Main outcome measures Number of grams of alcohol consumed per week, in total, in off-trade (eg, at home) and in on-trade (eg, in pubs, restaurants).Results Primary interrupted time series analyses found that the introduction of MUP was associated with a drop in reported weekly total alcohol consumption of 5.94 g (95% CI 1.29 to 10.60), a drop in off-trade consumption of 3.27 g (95% CI −0.01 to 6.56) and a drop in on-trade consumption of 2.67 g (95% CI −1.48 to 6.82). Associated reductions were larger for women than for men and were greater among heavier drinkers than for lighter drinkers, except for the 5% of heaviest drinking men for whom an associated increase in consumption was found. Secondary before-and-after analyses found that reductions in consumption were greater among older respondents and those living in less deprived areas. The introduction of MUP was not associated with a reduction in consumption among younger men and men living in more deprived areas.Conclusions Greater policy attention needs to be addressed to the heaviest drinking men, to younger men and to men who live in more deprived areas.

Background Initial results from the SCALA study demonstrated that training primary health care providers is an effective implementation strategy to increase alcohol screening in Colombia, Mexico and Peru, but did not show evidence of superior performance for the standard compared to the shorter training arm. This paper elaborates on those outcomes by examining the relationship of training-related process evaluation indicators with the alcohol screening practice. Methods A mix of convergent and exploratory mixed-methods design was employed. Data sources included training documentation, post-training questionnaires, observation forms, self-report forms and interviews. Available quantitative data were compared on outcome measure – providers’ alcohol screening. Results Training reach was high: three hundred fifty-two providers (72.3% of all eligible) participated in one or more training or booster sessions. Country differences in session length reflected adaptation to previous topic knowledge and experience of the providers. Overall, 49% of attendees conducted alcohol screening in practice. A higher dose received was positively associated with screening, but there was no difference between standard and short training arms. Although the training sessions were well received by participants, satisfaction with training and perceived utility for practice were not associated with screening. Profession, but not age or gender, was associated with screening: in Colombia and Mexico, doctors and psychologists were more likely to screen (although the latter represented only a small proportion of the sample) and in Peru, only psychologists. Conclusions The SCALA training programme was well received by the participants and led to half of the participating providers conducting alcohol screening in their primary health care practice. The dose received and the professional role were the key factors associated with conducting the alcohol screening in practice. Plain Language Summary: Primary health care providers can play an important role in detecting heavy drinkers among their consulting patients, and training can be an effective implementation strategy to increase alcohol screening and detection. Existing training literature predominantly focuses on evaluating trainings in high-income countries, or evaluating their effectiveness rather than implementation. As part of SCALA (Scale-up of Prevention and Management of Alcohol Use Disorders in Latin America) study, we evaluated training as implementation strategy to increase alcohol screening in primary health care in a middle-income context. Overall, 72.3% of eligible providers attended the training and 49% of training attendees conducted alcohol screening in practice after attending the training. Our process evaluation suggests that simple intervention with sufficient time to practice, adapted to limited provider availability, is optimal to balance training feasibility and effectiveness; that booster sessions are especially important in context with lower organizational or structural support; and that ongoing training refinement during the implementation period is necessary.

The World Health Organization has called on economic operators to “substitute, whenever possible, higher-alcohol products with no-alcohol and lower-alcohol products in their overall product portfolios, with the goal of decreasing the overall levels of alcohol consumption in populations and consumer groups, while avoiding the circumvention of existing regulations for alcoholic beverages and the targeting of new consumer groups with alcohol marketing, advertising and promotional activities” (see [...]

Abstract Background Confinement due to COVID-19 has increased mental ill-health. Few studies unpack the risk and protective factors associated with mental ill-health and addictions that might inform future preparedness. Methods Cross-sectional on-line survey with 37,810 Catalan residents aged 16+ years from 21 April to 20 May 2020 reporting prevalence of mental ill-health and substance use and associated coping strategies and behaviours. Results Weighted prevalence of reported depression, anxiety and lack of mental well-being was, respectively, 23, 26, and 75%, each three-fold higher than before confinement. The use of prescribed hypnosedatives was two-fold and of non-prescribed hypnosedatives ten-fold higher than in 2018. Women, younger adults and students were considerably more likely, and older and retired people considerably less likely to report mental ill-health. High levels of social support, dedicating time to oneself, following a routine, and undertaking relaxing activities were associated with half the likelihood of reported mental ill-health. Worrying about problems living at home, the uncertainty of when normality would return, and job loss were associated with more than one and a half times the likelihood of mental ill-health. With the possible exception of moderately severe and severe depression, length of confinement had no association with reported mental ill-health. Conclusions The trebling of psychiatric symptomatology might lead to either to under-identification of cases and treatment gap, or a saturation of mental health services if these are not matched with prevalence increases. Special attention is needed for the younger adult population. In the presence of potential new confinement, improved mental health literacy of evidence-based coping strategies and resilience building are urgently needed to mitigate mental ill-health.

In this work, reduction of alcoholic strength was discussed as a means to reduce consumption and alcohol-attributable harm. Statistical modelling was conducted to (1) estimate its potential for the largest six Western and Central European countries (France, Germany, Italy, Poland, Spain, UK); (2) calculate the increase in taxation necessary to reach this potential, and (3) estimate the mortality gains achieved with the introduction of no- or low-alcohol beverages in the UK and Spain. The high public health potential of reducing alcoholic strength was demonstrated via modelling a scenario in which the strength of all beverages was reduced by 10%, which would avert thousands of deaths in these six European countries per year. However, methods by which to achieve these gains were not clear, as the alcohol industry has shown no inclination toward reductions in the alcoholic strength of beer, wine, or spirits via a reformulation on a large scale. The increase of excise taxation to achieve the public health gains of such a reduction would result in markedly increasing prices—a situation unlikely to be implemented in Europe. Finally, the introduction of beer and wine with an alcoholic strength below 0.5% led to some substitutions of higher-strength beverages, but did not show a marked public health impact. New taxation initiatives to achieve the potential of a reduction of alcoholic strength will need to be implemented.

Abstract Background During development, excessive osteogenic differentiation of mesenchymal progenitor cells (MPC) within the cranial sutures can lead to premature suture fusion or craniosynostosis, leading to craniofacial and cognitive issues. Saethre-Chotzen syndrome (SCS) is a common form of craniosynostosis, caused by TWIST-1 gene mutations. Currently, the only treatment option for craniosynostosis involves multiple invasive cranial surgeries, which can lead to serious complications. Methods The present study utilized Twist-1 haploinsufficient (Twist-1 del/+) mice as SCS mouse model to investigate the inhibition of Kdm6a and Kdm6b activity using the pharmacological inhibitor, GSK-J4, on calvarial cell osteogenic potential. Results This study showed that the histone methyltransferase EZH2, an osteogenesis inhibitor, is downregulated in calvarial cells derived from Twist-1 del/+ mice, whereas the counter histone demethylases, Kdm6a and Kdm6b, known promoters of osteogenesis, were upregulated. In vitro studies confirmed that siRNA-mediated inhibition of Kdm6a and Kdm6b expression suppressed osteogenic differentiation of Twist-1 del/+ calvarial cells. Moreover, pharmacological targeting of Kdm6a and Kdm6b activity, with the inhibitor, GSK-J4, caused a dose-dependent suppression of osteogenic differentiation by Twist-1 del/+ calvarial cells in vitro and reduced mineralized bone formation in Twist-1 del/+ calvarial explant cultures. Chromatin immunoprecipitation and Western blot analyses found that GSK-J4 treatment elevated the levels of the Kdm6a and Kdm6b epigenetic target, the repressive mark of tri-methylated lysine 27 on histone 3, on osteogenic genes leading to repression of Runx2 and Alkaline Phosphatase expression. Pre-clinical in vivo studies showed that local administration of GSK-J4 to the calvaria of Twist-1 del/+ mice prevented premature suture fusion and kept the sutures open up to postnatal day 20. Conclusion The inhibition of Kdm6a and Kdm6b activity by GSK-J4 could be used as a potential non-invasive therapeutic strategy for preventing craniosynostosis in children with SCS. Graphical abstract Pharmacological targeting of Kdm6a/b activity can alleviate craniosynostosis in Saethre-Chotzen syndrome. Aberrant osteogenesis by Twist-1 mutant cranial suture mesenchymal progenitor cells occurs via deregulation of epigenetic modifiers Ezh2 and Kdm6a/Kdm6b. Suppression of Kdm6a- and Kdm6b-mediated osteogenesis with GSK-J4 inhibitor can prevent prefusion of cranial sutures.

The planet is presently undergoing dramatic changes caused by human activities. We are living in the era of the Anthropocene, where our activities directly affect all living organisms on Earth. Insects constitute a major part of the world’s biodiversity and currently, we see dwindling insect biomass but also outbreaks of certain populations. Most insects rely on chemical communication to locate food, mates, and suitable oviposition sites, but also to avoid enemies and detrimental microbes. Emissions of, e.g., CO2, NOx, and ozone can all affect the chemical communication channel, as can a rising temperature. Here, we present a review of the present state of the art in the context of anthropogenic impact on insect chemical communication. We concentrate on present knowledge regarding fruit flies, mosquitoes, moths, and bark beetles, as well as presenting our views on future developments and needs in this emerging field of research. We include insights from chemical, physiological, ethological, and ecological directions and we briefly present a new international research project, the Max Planck Centre for Next Generation Insect Chemical Ecology (nGICE), launched to further increase our understanding of the impact of human activities on insect olfaction and chemical communication.

British supermarket-panel data suggest no increases in overall sales and purchases of alcohol following COVID-19 lockdowns, yet survey and mortality data suggest otherwise. This paper attempts to unravel the paradox. Based on purchase data of 79,417 British households from Kantar Worldpanel, we undertake controlled interrupted time series analysis of the impact of COVID-19 confinement introduced on 23rd March 2020, and variably applied during 2020, compared to purchases during 2015 to 2019 as controls. We also undertook Poisson regression analyses to estimate if changes in purchases differed by household socio-demographic and economic factors. Excess off-trade household alcohol purchases (expressed as grams of ethanol) following the introduction of confinement, were 29.2% higher (95% CI = 25.8% to 32.5%) for the post-confinement months of 2020, being larger until mid-July 2020 (37.5%, 95%CI = 33.9 to 41.26%) when pubs re-opened with restrictions, and smaller (24.6%, 95%CI = 21.6 to 27.7) thereafter. During the time of complete pub closures, and fully adjusting for no on-trade purchases, household purchases of alcohol did not change when compared with the same time period during 2015–2019 (coefficient = -0.9%, 95%CI = -5.6 to 3.8). Excess purchases from 23rd March to 31st December 2020 varied by region of Great Britain, being higher in the north of England, and lower in Scotland and Wales. Excess purchases were greater in the most deprived households, compared with the least deprived households. Excess purchases increased substantially as the amount of alcohol normally purchased by a household increased, with the top one fifth of households that normally bought the most alcohol increasing their purchases more than 17 times than the bottom one fifth of households that bought the least alcohol. That the heaviest buyers of alcohol increased their purchases the most, with some independent impact of socio-economic disadvantage, might explain why reported alcohol problems and recent alcohol-related death rates might have increased. A conclusion of this is that alcohol policy to reduce high consumption of alcohol, and the availability of help and treatment to reduce alcohol consumption become more important during extraordinary times, such as COVID lockdowns.

BackgroundBy adopting Agenda 2030, governments agreed to review and report on their approach and action for achievement of sustainable development goals annually through the High-Level Political Forum (HLPF) on Sustainable Development. Health and well-being are at the heart of the United Nations Agenda 2030. Given the social and economic harm that can be done by alcohol, reducing the consumption of alcohol is a pre-requisite to achieve the sustainable development goals. We explored how selected European countries have considered alcohol-related harm as an obstacle to achievement of SDGs and the extent to which they view alcohol policy as a solution to the achievement of sustainable development by analysing their voluntary national reviews (VNRs) submitted to the HLPF between years 2016 and 2020.MethodsWe developed our own framework with 260 questions reflecting three dimensions of alcohol-harm considerations: indication, action, and evaluation. We analysed 36 VNRs of 32 European countries by first assessing them against the 260 questions to find out how they report on alcohol harm and whether they, in their action, refer to evidence-based, cost-effective alcohol policy solutions. Afterwards we used content analysis to assess the extent to which the countries addressed alcohol related harm, whether they refer to alcohol harm within SDG 3 (good health and well-being) or look beyond the health goal and consider alcohol harm having impact on goals other than the Goal 3.FindingsNine countries (28.1%) did not mention alcohol in their report. Only eight countries (25%) mentioned one or more of the alcohol policy best buys among the actions they are taking to reduce alcohol related harm and only three (9.3%) explicitly elaborated on their impact on goals other than goal 3. Only five countries referred to the agreed indicator 3.5.2 measuring alcohol per capita consumption in the adult population. Many of the remaining countries used a range of terminology rather than alcohol per capita consumption, including "excessive use of alcohol", "heavy use", "too much alcohol ", "harmful alcohol consumption", "use among young people".InterpretationAlcohol use is, for example, associated with violence (SDG 5 and 16), it contributes to inequalities (SDG 5 and 10), it hinders economic growth (SDG 8), disrupts sustainable consumption (SDG 12) and it adversely impacts environment (SDG 13 and 14). The findings of this study show that these effects are not considered in the design of measures to achieve these goals. Moreover, inaccurate language related to alcohol harm indicates a gap in understanding of extend of alcohol burden and the consequences for sustainable development. So does the choice of ineffective measures to reduce alcohol consumption. Education programs and awareness raising campaigns focusing on individual lifestyle are neither in line with WHO Global Strategy to reduce the harm caused by alcohol that all selected countries adopted in 2010, nor do they reflect the seriousness of the problems related to alcohol use. Effective alcohol policy measures, so called three best buys, are missing from the transformative action that the Agenda 2030 calls for and governments committed to.

Oilseed rape (OSR; Brassica napus) is a globally important crop which is increasingly under pressure from pests, pathogens and weeds. We investigated the potential of achieving multifunctional crop protection benefits by intercropping oilseed rape with legumes. A field experiment was conducted in which winter oilseed rape was intercropped with the annual frost sensitive legumes berseem clover (Trifolium alexandrinum) or spring faba bean (Vicia faba), or with the winter grain legumes winter faba bean or winter peas (Pisum sativum). We tracked damage to winter oilseed rape by autumn and spring pests (slugs and insects), pathogens, weed biomass, as well as oilseed rape and intercrop yield in each treatment. Intercropping treatments resulted in pest damage that was equivalent or lower than in oilseed rape alone. Follow up field and lab assessments for the frost sensitive legume intercrops provided evidence for a reduction in autumn pest damage to OSR. Each legume intercrop had its own benefits and drawbacks in relation to pest, pathogen and weed suppression, suggesting that the plant species selected for intercropping with oilseed rape should be based on the pests, pathogens and weeds of greatest concern locally to achieve relevant multifunctional benefits. Our study provides a framework for further experiments in which the multifunctional effects of intercropping on pests, pathogens and weeds can be quantified.

In its action plan (2022–2030) to reduce the harmful use of alcohol, the WHO calls on economic operators to “substitute, whenever possible, higher-alcohol products with no-alcohol and lower-alcohol products in their overall product portfolios, with the goal of decreasing the overall levels of alcohol consumption in populations and consumer groups”. This paper investigates substitution at the level of the consumer, based on Spanish household purchase data. ARIMA modelling of market research data of 1.29 million alcohol purchases from 18,954 Spanish households is used to study the potential impact of lower-strength alcohol products and the impact of beer prices in reducing household purchases of grams of alcohol between the 2nd quarter of 2017 and 1st quarter of 2022. Reducing the alcohol strength of existing higher-strength beers and wines had a much greater associated impact on reducing the purchases of all grams of alcohol than the relatively small increases in purchases of no-alcohol beers (ABV ≤ 1.0%) and zero-alcohol wines (ABV = 0.0%). For beers, the relative price per gram of alcohol decreased with the increasing ABV of the beer. Increasing the price per gram of alcohol in beers with an ABV > 3.5%, adjusted for the ABV of the beer, was associated with much greater increases in purchases of no-alcohol beers (ABV ≤ 1.0%) and much greater decreases in purchases of all grams of alcohol than decreases in the price of no-alcohol beers or increases in the price of beers with an ABV > 3.5% unadjusted for ABV. Thus, a key to reducing purchases of grams of alcohol, which also results in increased purchases of no-alcohol beers, is to increase the price of higher strength beers (ABV > 3.5%) with the price per gram of alcohol increasing as the ABV of the product increases.

**Background**: Trauma remains a leading cause of morbidity and mortality in Australia. The objective of this South Australian study was to analyse epidemiological trends in facial fractures and assess the relationship between socioeconomic disadvantage and clinical outcomes. **Method**: A retrospective analysis of the relationship was conducted between socioeconomic disadvantage and facial fractures. All paediatric and adult patients with facial fractures who attended the Royal Adelaide Hospital and the Women’s and Children’s Hospital Adelaide between January 2012 and January 2017 either as in- or outpatients. The medical records, progress notes, imaging and operative notes from plastics, craniofacial and oral maxillofacial surgery teams were retrospectively collated into a registry and reviewed. Ethics approval was granted from the RAH Human Research and Ethics Committee [HREC/17/RAH/402]. **Results**: A total of 2559 patients, 1976 males (77.2%) and 583 females (22.8%), sustained a facial fracture. The most disadvantaged group had the highest proportion of facial fractures (36.9%), with the highest incidence in the 25–34 age group (22.4%). Assaults were the most common injury with decreasing odds as socioeconomic advantage increased (p

**Background**: Trauma remains a leading cause of morbidity and mortality in Australia. The objective of this South Australian study was to analyse epidemiological trends in facial fractures and assess the relationship between socioeconomic disadvantage and clinical outcomes. **Method**: A retrospective analysis of the relationship was conducted between socioeconomic disadvantage and facial fractures. All paediatric and adult patients with facial fractures who attended the Royal Adelaide Hospital and the Women’s and Children’s Hospital Adelaide between January 2012 and January 2017 either as in- or outpatients. The medical records, progress notes, imaging and operative notes from plastics, craniofacial and oral maxillofacial surgery teams were retrospectively collated into a registry and reviewed. Ethics approval was granted from the RAH Human Research and Ethics Committee [HREC/17/RAH/402]. **Results**: A total of 2559 patients, 1976 males (77.2%) and 583 females (22.8%), sustained a facial fracture. The most disadvantaged group had the highest proportion of facial fractures (36.9%), with the highest incidence in the 25–34 age group (22.4%). Assaults were the most common injury with decreasing odds as socioeconomic advantage increased (p

Summary: Background: As a policy option to reduce consumption of alcohol and the harm it does, on May 1, 2018, Scotland introduced a minimum price of 50 British pence (p) per unit of alcohol (8 g) sold; Wales followed suit on March 2, 2020, with the same minimum unit price (MUP). We analysed household purchase data based on bar codes to assess the impact of these policy options in the medium term for Scotland and in the immediate term for Wales. Methods: For these location-controlled, interrupted time series regression analyses, the data source was Kantar WorldPanel's household shopping panel, which, at the time of our analysis, included 35 242 British households providing detailed information on 1·24 million separate alcohol purchases in 2015–18 and the first half of 2020. With no data exclusions, we analysed the impact of introducing MUP in Scotland, using purchases in northern England as control, and in Wales, using western England as control. The studied changes associated with MUP were price paid per gram of alcohol purchased, grams of alcohol purchased, and amount of money spent on alcohol. Findings: In Scotland, price increases and purchase decreases following the introduction of MUP in 2018 were maintained during the first half of 2020. The difference between Scotland and northern England in 2020 was a price increase of 0·741 p per gram (95% CI 0·724–0·759), a 7·6% increase, and a purchase decrease of 7·063 g per adult per household per day that an alcohol purchase was made (6·656–7·470), a 7·7% decrease. In Wales, the introduction of MUP led to similar results. The difference between Wales and western England was a price increase 0·841 of 0·841 p per gram (0·732–0·951), an 8·2% increase, and a purchase decrease of 7·052 g per adult per household per day that an alcohol purchase was made (6·463–7·640), an 8·6% decrease. For both Scotland and Wales, reductions in overall purchases of alcohol were largely restricted to households that bought the most alcohol. The introduction of MUP was not associated with an increased expenditure on alcohol by households that generally bought small amounts of alcohol and, in particular, those with low incomes. The changes were not affected by the introduction of COVID-19 confinement in the UK on March 26, 2020. Interpretation: The evidence base supporting the positive, targeted impact of MUP is strengthened by the comparable results for Scotland and Wales. The short-term impact of MUP in Scotland during 2018 is maintained during the first half of 2020. MUP is an effective alcohol policy option to reduce off-trade purchases of alcohol and should be widely considered. Funding: None.

This paper reports the result of a realist review based on a theory of change that substitution of higher strength alcohol products with lower strength alcohol products leads to decreases in overall levels of alcohol consumption in populations and consumer groups. The paper summarizes the results of 128 publications across twelve different themes. European consumers are increasingly buying and drinking lower strength alcohol products over time, with some two fifths doing so to drink less alcohol. It tends to be younger more socially advantaged men, and existing heavier buyers and drinkers of alcohol, who take up lower strength alcohol products. Substitution leads to a lower number of grams of alcohol bought and drunk. Although based on limited studies, buying and drinking lower strength products do not appear to act as gateways to buying and drinking higher strength products. Producer companies are increasing the availability of lower strength alcohol products, particularly for beer, with extra costs of production offset by income from sales. Lower strength alcohol products tend to be marketed as compliments to, rather than substitutes of, existing alcohol consumption, with, to date, the impact of such marketing not evaluated. Production of lower strength alcohol products could impair the impact of existing alcohol policy through alibi marketing (using the brand of lower strength products to promote higher strength products), broadened normalization of drinking cultures, and pressure to weaken policies. In addition to increasing the availability of lower strength products and improved labelling, the key policy that favours substitution of higher strength alcohol products with lower strength products is an alcohol tax based on the dose of alcohol across all products.

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk.

In its action plan (2022–2030) to reduce the harmful use of alcohol, the WHO calls on economic operators to “substitute, whenever possible, higher-alcohol products with no-alcohol and lower-alcohol products in their overall product portfolios, with the goal of decreasing the overall levels of alcohol consumption in populations and consumer groups”. In this paper, we investigate substitution at the level of the consumer based on Spanish household purchase data. ARIMA modelling of market research data of 1.29 million alcohol purchases from 18,954 Spanish households is used to study the potential impact of lower-strength alcohol products on reducing household purchases of grams of alcohol between the second quarter of 2017 and the first quarter of 2022. For households that recently bought either no-alcohol beer or wine (ABV ≤ 0.5%), the subsequent associated purchases of higher-strength beers and wines, respectively, and total grams of alcohol were reduced, the more so the higher the volume of initial purchases of beers and wines. The introduction of 20% ABV variants of same-branded 40% ABV whisky and gin during early 2021 was associated with reduced purchases of grams of alcohol within all spirits and of total grams of alcohol as a result of switching from other spirits products to the 20% variants, although not associated with reduced purchases of grams of alcohol within all variants of the studied same-branded whisky and gin; instead, an increase was observed in this category. With respect to Spanish household purchase data, the evidence behind the WHO’s call for substitution is substantiated. Further research across different jurisdictions is needed to provide ongoing monitoring of the impact of potential substitution on consumer behavior and public health, including unintended consequences, with findings from research informing future alcohol policies at all levels.

Abstract Background Deciphering the molecular mechanisms mediating the chemical senses, taste, and smell has been of vital importance for understanding the nature of how insects interact with their chemical environment. Several gene families are implicated in the uptake, recognition, and termination of chemical signaling, including binding proteins, chemosensory receptors and degrading enzymes. The cotton leafworm, Spodoptera littoralis, is a phytophagous pest and current focal species for insect chemical ecology and neuroethology. Results We produced male and female Illumina-based transcriptomes from chemosensory and non-chemosensory tissues of S. littoralis, including the antennae, proboscis, brain and body carcass. We have annotated 306 gene transcripts from eight gene families with known chemosensory function, including 114 novel candidate genes. Odorant receptors responsive to floral compounds are expressed in the proboscis and may play a role in guiding proboscis probing behavior. In both males and females, expression of gene transcripts with known chemosensory function, including odorant receptors and pheromone-binding proteins, has been observed in brain tissue, suggesting internal, non-sensory function for these genes. Conclusions A well-curated set of annotated gene transcripts with putative chemosensory function is provided. This will serve as a resource for future chemosensory and transcriptomic studies in S. littoralis and closely related species. Collectively, our results expand current understanding of the expression patterns of genes with putative chemosensory function in insect sensory and non-sensory tissues. When coupled with functional data, such as the deorphanization of odorant receptors, the gene expression data can facilitate hypothesis generation, serving as a substrate for future studies.

Background Screening, brief intervention and referral to treatment (SBIRT) is a programme to reduce alcohol consumption for drinkers with high alcohol consumption levels. Only 2.9% of patients in primary health care (PHC) are screened for their alcohol use in Germany, despite high levels of alcohol consumption and attributable harm. We developed an open-access simulation model to estimate the impact of higher SBIRT delivery rates in German PHC settings on population-level alcohol consumption. Methods and findings A hypothetical population of drinkers and non-drinkers was simulated by sex, age, and educational status for the year 2009 based on survey and sales data. Risky drinking persons receiving BI or RT were sampled from this population based on screening coverage and other parameters. Running the simulation model for a ten-year period, drinking levels and heavy episodic drinking (HED) status were changed based on effect sizes from meta-analyses. In the baseline scenario of 2.9% screening coverage, 2.4% of the adult German population received a subsequent intervention between 2009 and 2018. If every second PHC patient would have been screened for alcohol use, 21% of adult residents in Germany would have received BI or RT by the end of the ten-year simulation period. In this scenario, population-level alcohol consumption would be 11% lower than it was in 2018, without any impact on HED prevalence. Screening coverage rates below 10% were not found to have a measurable effect on drinking levels. Conclusions Large-scale implementation of SBIRT in PHC settings can yield substantial reductions of alcohol consumption in Germany. As high screening coverage rates may only be achievable in the long run, other effective alcohol policies are required to achieve short-term reduction of alcohol use and attributable harm in Germany. There is large potential to apply this open-access simulation model to other settings and for other alcohol interventions.

Introduction Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare. Materials and methods Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status. Results 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained. Conclusions Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19.

Neonatal and adult strokes are more common in the left than in the right cerebral hemisphere in the middle cerebral arterial territory, and adult extracranial and intracranial vessels are systematically left-dominant. The aim of the research reported here was to determine whether the asymmetric vascular ground plan found in adults was present in healthy term neonates (n = 97). A new transcranial Doppler ultrasonography dual-view scanning protocol, with concurrent B-flow and pulsed wave imaging, acquired multivariate data on the neonatal middle cerebral arterial structure and function. This study documents for the first-time systematic asymmetries in the middle cerebral artery origin and distal trunk of healthy term neonates and identifies commensurately asymmetric hemodynamic vulnerabilities. A systematic leftward arterial dominance was found in the arterial caliber and cortically directed blood flow. The endothelial wall shear stress was also asymmetric across the midline and varied according to vessels’ geometry. We conclude that the arterial structure and blood supply in the brain are laterally asymmetric in newborns. Unfavorable shearing forces, which are a by-product of the arterial asymmetries described here, might contribute to a greater risk of cerebrovascular pathology in the left hemisphere.

Environmental variation experienced by a single genotype can induce phenotypic plasticity in various traits, such as behavioural, physiological and developmental characteristics. It can occur within the lifetime of an individual through within-generation phenotypic plasticity (WGP) or vertically across generations through transgenerational phenotypic plasticity (TGP). However, knowledge about TGP and the co-occurrence of WGP and TGP is still limited. In insect host-plant selection, the ability to alter phenotypic traits through WGP is well documented while the importance of TGP and the possible co-occurrence between the two is largely unknown. Host-plant selection of both larvae and adults of the polyphagous moth Spodoptera littoralis can be modified by previous experience through WGP. Thus, the aim of this study was to investigate if parental host-plant experience can influence host-plant choice behaviour and performance of S. littoralis offspring through TGP. For this, we tested effects of rearing parents on different host plants on the offspring’s first instar larval migration and host plant choice, larval development and adult oviposition. A transgenerational effect on larval development was found, with increased pupal weight on a matching host-plant diet to that of the parent, when larvae were reared on cotton (good larval host plant) while no such effect was found on maize (poor larval host plant). These findings indicate that TGP of S. littoralis progeny development traits may only occur under favourable conditions. Parental diet did not affect larval host plant choice or migration. Furthermore, no effect of parental diet was found on offspring oviposition behaviour, indicating that adult female host-plant selection is governed by innate preference hierarchy and WGP, rather than TGP. Thus, parental diet may influence offspring performance but not behaviour, indicating that WGP is most important for host-plant selection behaviours in S. littoralis, but TGP can affect progeny development. If so, the importance of different types of plasticity may vary among traits of S. littoralis associated with host plant utilisation.

Summary: Advances in the treatment of Ewing's sarcoma (EWS) are desperately needed, particularly in the case of metastatic disease. A deeper understanding of collateral sensitivity, where the evolution of therapeutic resistance to one drug aligns with sensitivity to another drug, may improve our ability to effectively target this disease. For the first time in a solid tumor, we produced a temporal collateral sensitivity map that demonstrates the evolution of collateral sensitivity and resistance in EWS. We found that the evolution of collateral resistance was predictable with some drugs but had significant variation in response to other drugs. Using this map of temporal collateral sensitivity in EWS, we can see that the path toward collateral sensitivity is not always repeatable, nor is there always a clear trajectory toward resistance or sensitivity. Identifying transcriptomic changes that accompany these states of transient collateral sensitivity could improve treatment planning for patients with EWS.

This study was a clinical review of infant positive expiratory pressure (PEP) therapy in young children with cystic fibrosis (CF). The aim of this study was to determine whether pressures of 10–20 cm H2O PEP therapy (recommended by the CF trust) are being achieved with routine airway clearance therapy. This took place at the Royal Hospital for Children, Glasgow a specialist UK CF centre. Values were obtained from 21 young children. Pressures above 10 cm H2O during tidal volume breathing were not achieved within our cohort. Further investigation is required to determine efficacy of lower pressures in PEP therapy with young children.