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Aims: Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre‐exposure prophylaxis to affect hormonal concentrations achieved from taking gender‐affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT. Methods: The study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took ≥12 weeks of TDF/FTC and then switched to ≥12 weeks of TAF/FTC for pre‐exposure prophylaxis. Results: Thirty‐nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT. Conclusion: There are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT. [ABSTRACT FROM AUTHOR]

Female herbivorous insects are expected to oviposit on the host plant providing the best performance of the offspring. However, in some insects the larvae are mobile and are not totally dependent on the mother's choice. They can change host plant when conditions for development or exposure to natural enemies vary between individual plants within a patch. Here we study larval migration and preference between two host plants, cotton and alfalfa, in the Egyptian leafworm, Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae). Previous studies have shown that although larval performance is better on cotton, females prefer to oviposit on alfalfa, and this preference corresponds to a higher survival of the eggs. In this study, S. littoralis larvae showed directed movement between host plants and were found to prefer alfalfa over cotton in field test in Egypt, as well as in laboratory selection of feeding site assays. To determine effects by natural enemies, the parasitism rates and various life‐history traits were measured for one larval parasitoid, Microplitis rufiventris Kokujev (Hymenoptera: Braconidae), on several host plants including cotton and clover (equivalent host plant to alfalfa). Overall, parasitism was higher on cotton and parasitoid performance (cocoon mass, adult longevity, and female egg load) was better on cotton compared to clover. This fact suggests an enemy‐free space on clover and alfalfa, as parasitism rate is higher on cotton, and the parasitoid performance is also better on cotton‐fed larvae. [ABSTRACT FROM AUTHOR]

Objectives: Retrospective harmonisation of data obtained through different instruments creates measurement error, even if the underlying concepts are assumed the same. We tested a novel method for item‐level data harmonisation of two widely used instruments that measure emotional and behavioural problems: the Child Behavior Checklist (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). Methods: Item content of the CBCL and SDQ was mapped onto four dimensions: emotional problems, peer relationship problems, hyperactivity/inattention and conduct problems. A diverse test sample was drawn from four prospective longitudinal birth cohort studies in Australia and Europe who used one or both instruments. The pooled sample included 5188 data points assessing children and adolescents aged 6–13 years (N = 257–704 participants per cohort). Measurement invariance was assessed using latent variable multi‐group confirmatory factor analysis. Results: Fifteen items from the CBCL and SDQ were mapped onto four dimensions allowing for measurement invariance testing as part of a stepwise process. Partial strict invariance between CBCL and SDQ assessments was established for all four dimensions. Conclusions: The harmonised dimensions of emotional, peer relationship, hyperactivity/inattention and conduct problems are invariant across the CBCL and SDQ suggesting that these dimensions can be reliably compared with limited measurement error. [ABSTRACT FROM AUTHOR]

Objective: Dysregulation of Fibroblast Growth Factor 10 (FGF10), a member of the family of Fibroblast Growth Factor (FGF) proteins, has been implicated in craniofacial and dental anomalies, including craniosynostosis, cleft palate, and Lacrimo‐Auriculo‐Dento‐Digital Syndrome. The aim of this murine study was to assess the craniofacial and dental phenotypes associated with a heterozygous FGF10 gene (FGF10+/−) mutation at skeletal maturity. Methods: Skulls of 40 skeletally mature mice, comprising two genotypes (heterozygous FGF10+/− mutation, n = 22; wildtype, n = 18) and two sexes (male, n = 23; female, n = 17), were subjected to micro‐computed tomography. Landmark‐based linear dimensions were measured for the cranial vault, maxilla, mandible, and first molar teeth. Multivariate analysis of variance was performed to assess whether there were significant differences in the craniofacial and dental structures between genotypes and sexes. Results: The craniomaxillary skeleton and the first molar teeth were smaller in the FGF10+/− mice (P <.05), but the mandible was unaffected. Sex did not have a significant effect on these structures (P >.05). Cranial sutural defects were noted in 5/22 (22.7%) mutant versus 2/18 (11.1%) wildtype mice, and cleft palate in only one (4.5%) mutant mouse. None of the mice displayed craniosynostosis, expansive bony lesions, bifid condyles, or impacted teeth. Conclusion: The FGF10+/− mutation was associated with craniomaxillary skeletal hypoplasia that probably arose from deficient (delayed) intramembranous ossification of the sutured bones. Overall, the skeletal and dental data suggest that the FGF10 gene plays an important role in the aetiology of craniofacial dysmorphology and malocclusion. [ABSTRACT FROM AUTHOR]

Aim: To examine the relationship between motor performance and attention in children born very preterm and at term, and investigate the presence of individual profiles of motor and attention performance. Method: Attention and motor performance at 7 and 13 years were assessed in 197 children born very preterm (52.5% male) and 69 children born at term (47.8% male) between 2001 and 2003. Linear regression models were fitted including an interaction term for birth group. Subgroups of children with similar attention and motor performance profiles were identified using latent profile analysis. Results: Balance was positively associated with all attention outcomes at both ages (p < 0.006). There were specific birth group interactions for aiming and catching and manual dexterity with attention at 13 years, with positive associations observed only for children born very preterm (p < 0.001). At 7 years, three profiles were observed: average attention and motor functioning; average motor functioning and low attention functioning; and low attention and motor functioning. At 13 years, two profiles of average attention and motor functioning emerged, as well as one profile of below-average attention and motor functioning. Children born very preterm were overrepresented in the lower functioning profiles (born very preterm 56%; born at term 29%). Interpretation: Motor functioning at age 7 years may be a useful marker of later attention skills, particularly for children born very preterm who are at greater risk of poorer long-term cognitive outcomes. [ABSTRACT FROM AUTHOR]

Alopecia area (AA) is a common autoimmune disorder, characterized by hair loss. Although its impact on quality of life is fairly well understood, studies on the economic impact of AA are limited. The aim of this study was to quantify the personal and nationwide economic burden of AA in Japan. Data were drawn from the Adelphi AA Disease Specific Programme (DSP)™, a real‐world, cross‐sectional survey with retrospective data collection, of Japanese physicians and patients with AA. The study was conducted in 2021, before the approval of Janus kinase inhibitors for AA. Physicians and their consulting AA patients completed questionnaires regarding disease severity, treatment, and AA‐related costs. The Work Productivity and Activity Impairment questionnaire was used to evaluate the impact of AA on patients' work and activity. Nationwide estimates of cost and productivity loss were extrapolated from collected patient data. A total of 50 physicians provided data on 235 patients; 58.7% were female, mean ± SD age was 41.1 ± 11.8 years, and mean physician‐estimated scalp hair loss was 40.4% ± 30.2%. Prescription medication use was high (92.3% of patients), but the use of over‐the‐counter medication was low, at 8.7%. Mean cost to patients for medication was ¥ 4263 (US$ 32.42) per month. Productivity while at work (presenteeism) was significantly impaired (23.9% ± 25.7%), but absenteeism was low (0.9% ± 2.8%). The total nationwide cost of AA was estimated at 112.7 billion yen (US$ 857 million), of which 88.1 billion yen (78.2%) was due to productivity loss. Over 2 million days per year of activity time were estimated to be lost due to AA. Thus, despite not being a physically limiting disease, AA has a significant impact in terms of cost and time, both on a personal and national level. These data highlight the need for more targeted interventions to reduce the effects of AA on the Japanese economy. [ABSTRACT FROM AUTHOR]

Aim: Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long‐term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. Methods: Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016–2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. Results: Seventy‐six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92–3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) −1.3 (−2.7, 0.1) and motor composite score adjusted coefficient (95% CI) −1.3 (−2.8, 0.2). Conclusion: Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

This meta‐analysis examined the relationship between prenatal maternal stress and/or anxiety and the outcomes of children aged 3 months to 9 years. Of the 8754 studies published before June 2021 that were synthesized, 17 conducted in Western countries were included in the meta‐analysis (Ntotal = 23,307; Mmales 54%; Methnicity White 77%, Pacific 15%, African American/Black 10%, Middle Eastern 7%, Eastern 8%). Effect sizes ranged from −0.41 to 0.15. A weak negative association was found between prenatal stress and/or anxiety exposure and children's general intellectual development. Associations varied based on the type of exposure. Findings are limited to developed counties and cannot be generalized to low‐ and middle‐income countries. Directions for maternal prenatal intervention and future studies are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol screening, brief advice and referral to treatment (SBIRT) in primary health care is an effective strategy to decrease alcohol consumption at population level. However, there is relatively scarce evidence regarding its economic returns in non‐high‐income countries. The current paper aims to estimate the return‐on‐investment of implementing a SBIRT program in Mexican primary health‐care settings. Methods: Empirical data was collected in a quasi‐experimental study, from 17 primary health‐care centres in Mexico City regarding alcohol screening delivered by 145 health‐care providers. This data was combined with data from a simulation study for a period of 10 years (2008 to 2017). Economic investments were calculated from a public sector health‐care perspective as clinical consultation costs (salary and material costs) and program costs (set‐up, adaptation, implementation strategies). Economic return was calculated as monetary gains in the public sector health‐care, estimated via simulated reductions in alcohol consumption, dependent on population coverage of alcohol interventions delivered to primary health‐care patients. Results: Results showed that scaling up a SBIRT program in Mexico over a 10‐year period would lead to positive return‐on‐investment values ranging between 21% in scenario 4 (confidence interval −8.6%, 79.5%) and 110% in scenario 5 (confidence interval 51.5%, 239.8%). Moreover, over the 10‐year period, up to 16,000 alcohol‐related deaths could be avoided as a result of implementing the program. Discussion and Conclusions: SBIRT implemented at national level in Mexico may lead to substantial financial gains from a public sector health‐care perspective. [ABSTRACT FROM AUTHOR]

Thus, there is great interest in interventions that improve children's working memory, such as available working memory training programmes and understanding which children benefit most. Abbreviations ADHD attention deficit/hyperactiviy disorder CI confidence interval Grit-S short grit scale IQ intellectual quotient SD standard deviation Cognitive training programmes typically require intensive practice on challenging activities and can improve children's core cognitive abilities such as working memory for up to 6 months.[[1]] Working memory, the ability to briefly hold information in mind and work with it, is important for cognitive, behavioural and academic functioning and is more likely to be reduced in children with neurodevelopmental disorders than typically developing peers. [Extracted from the article]

Young age has consistently correlated with lower adherence to pre‐exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Digital medicine, a dynamic healthcare platform of wearable physiological sensors and mobile communication technology that can respond to medication nonadherence rapidly, has the potential in promoting PrEP adherence. We evaluated the feasibility and acceptability of Proteus Discover, a digital monitoring adherence system, to measure PrEP adherence and provide real‐time feedback among cisgender YMSM and transgender women. One hundred HIV‐negative young men and transgender women ages 16–24 years were enrolled in a 24‐week randomized controlled crossover study to tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) coencapsulated with Proteus Discover versus TDF/FTC standard‐of‐care. Participants in the 12‐week Proteus Discover arm received weekly SMS text messages to promote pill taking based on Proteus Discover adherence data. Dried blood spots (DBS) were collected at 4‐week intervals for tenofovir diphosphate (TFV‐DP) in red blood cells as the referent and questionnaires were completed to assess acceptability, usability, and patterns of use. Linear mixed models analyzed the relationship between 30‐day adherence measured by DBS and Proteus Discover. PrEP adherence was high overall. Adherence, as measured by DBS, was correlated with adherence as measured by Proteus Discover (p value = 0.03). Most participants reported that Proteus Discover helped them take their PrEP daily and that the system was easy to use. However, a majority (53.5%–60.5%) disagreed with the statement that wearing the patch was not an issue. There was an incremental increase in TFV‐DP in DBS with adherence by Proteus Discover. More research is warranted to explore optimizing PrEP adherence for youth through real‐time monitoring. [ABSTRACT FROM AUTHOR]

Aim: To describe the presence and nature of parent concerns regarding the development of their children admitted to Australian neonatal units (NNUs), comprising neonatal intensive care or special care. Methods: In a cross‐sectional survey, mothers and fathers provided information regarding concerns for their child's development. The self‐administered survey was completed by two separate cohorts; (i) parents of child graduates from Australian NNUs (n = 381); (ii) parents of infant's inpatient in two South Australian NNUs (n = 209). Data were analysed using thematic analysis and descriptive statistics. Results: Information was provided for 730 children. Developmental concern was reported for 39% of NNU graduates and 35% of inpatients. Children born very preterm (< 32 weeks' gestation) elicited greater parent concern than those born more mature (Cohort 1: 41% vs 36%; Cohort 2: 49% vs 22%), including in multiple developmental domains (Cohort 1: 17% vs 15%; Cohort 2: 28% vs 4%). Parents with inpatient infants were predominantly concerned about general development‐milestones (19.1%) and the potential impact of medical or CNS issues (13.7%). Graduate parents commonly focused on specific domains, such as their child's speech‐language (13.7%) and motor (12.9%) development. Conclusion: Neurodevelopment is a substantial source of concern for mothers and fathers during NNU admission and childhood, particularly for children born very preterm. However, in the first year of life, developmental concerns are poorly defined. This highlights the need for clinical education resources detailing infant developmental expectations and supportive strategies for parents of these high‐risk infants. [ABSTRACT FROM AUTHOR]

Background: Although outcomes for infants born extremely low birthweight (ELBW; <1000 g birthweight) have improved over time, it is important to document survival and morbidity changes following the advent of modern neonatal intensive care in the 1990s. Objective: To describe trends in survival, perinatal outcomes and neurodevelopment to 2 years' corrected age over time across six discrete geographic cohorts born ELBW between 1979 and 2017. Methods: Analysis of data from discrete population‐based prospective cohort studies of all live births free of lethal anomalies with birthweight 500–999 g in the state of Victoria, Australia, over 6 eras: 1979–80, 1985–87, 1991–92, 1997, 2005 and 2016–17. Perinatal data collected included survival, duration and type of respiratory support, neonatal morbidities and two‐year neurodevelopmental outcomes. Results: More ELBW live births were inborn (born in a maternity hospital with a neonatal intensive care unit) over time (1979–80, 70%; 2016–17, 84%), and more were offered active care (1979–80, 58%; 2016–17, 90%). Survival to 2 years rose substantially, from 25% in 1979–80 to 80% in 2016–17. In survivors, rates of any assisted ventilation rose from 75% in 1979–80 to 99% in 2016–17. Cystic periventricular leukomalacia, severe retinopathy of prematurity and blindness improved across eras. Two‐year data were available for 95% (1054/1109) of survivors. Rates of cerebral palsy, deafness and major neurodevelopmental disability changed little over time. The annual numbers with major neurodevelopmental disability increased from 12.5 in 1979–80 to 30 in 2016–17, but annual numbers free of major disability increased much more, from 31 in 1979–80 to 147 in 2016–17. Conclusions: Active care and survival rates in ELBW children have increased dramatically since 1979 without large changes in neonatal morbidities. The numbers of survivors free of major neurodevelopmental disability have increased more over time than those with major disability. [ABSTRACT FROM AUTHOR]

Pesticide resistance development is an example of rapid contemporary evolution that poses immense challenges for agriculture. It typically evolves due to the strong directional selection that pesticide treatments exert on herbivorous arthropods. However, recent research suggests that some species are more prone to evolve pesticide resistance than others due to their evolutionary history and standing genetic variation. Generalist species might develop pesticide resistance especially rapidly due to pre‐adaptation to handle a wide array of plant allelochemicals. Moreover, research has shown that adaptation to novel host plants could lead to increased pesticide resistance. Exploring such cross‐resistance between host plant range evolution and pesticide resistance development from an ecological perspective is needed to understand its causes and consequences better. Much research has, however, been devoted to the molecular mechanisms underlying pesticide resistance while both the ecological contexts that could facilitate resistance evolution and the ecological consequences of cross‐resistance have been under‐studied. Here, we take an eco‐evolutionary approach and discuss circumstances that may facilitate cross‐resistance in arthropods and the consequences cross‐resistance may have for plant–arthropod interactions in both target and non‐target species and species interactions. Furthermore, we suggest future research avenues and practical implications of an increased ecological understanding of pesticide resistance evolution. [ABSTRACT FROM AUTHOR]

Background: We assessed cumulative antiretroviral exposure—using tenofovir diphosphate (TFV‐DP) in dried blood spots (DBS)—in persons with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)‐based antiretroviral therapy (ART) as single‐tablet regimens (STR) or multiple‐tablet regimens (MTR). Methods: Blood for DBS was prospectively collected in PWH on TDF during 1144 person visits (n = 523). Linear mixed‐effects models, adjusted for baseline characteristics, were used to compare TFV‐DP in STR versus MTR. Models adjusted for ART regimen using either anchor drug class, pharmacokinetic booster status (unboosted [u/] or boosted [b/]), or a combined STR/MTR and booster categorical variable. Results: In the anchor class‐adjusted model, STR had 19% (95% confidence interval [CI]: 3%–37%; p = 0.02) higher TFV‐DP concentrations than MTR. However, in the booster‐adjusted model, STR was not significantly higher than MTR (estimate 5%, 95% CI: −9% to 21%; p = 0.48), although PWH on b/ART had 35% (95% CI: 16%–58%; p = 0.0001) higher TFV‐DP than u/ART. In the STR/MTR‐boosted variable model, when compared to u/MTR, b/STR, b/MTR, and u/STR had 25% (95% CI: 7%–47%; p = 0.005), 37% (95% CI: 17%–59%; p < 0.0001), and 7% (95% CI: −7% to 24%; p = 0.34) higher TFV‐DP, respectively. Compared with b/MTR, b/STR had 9% (95% CI: −31% to 10%; p = 0.37) lower TFV‐DP. In a sensitivity analysis of PWH with HIV viral load <20 copies/ml at all visits, b/STR and b/MTR had 34% (95% CI: 16%–55%; p < 0.0001) and 12% (95% CI: −2% to 27%; p = 0.09) higher TFV‐DP, respectively, compared with u/MTR, while u/STR had 4% (95% CI: −15% to 8%; p = 0.50) lower TFV‐DP. Compared with b/MTR, b/STR had 17% (95% CI: 2%–30%; p = 0.03) higher TFV‐DP. Conclusions: Persons with HIV on b/TDF‐based ART had higher TFV‐DP than u/ART, regardless of STR or MTR use. No significant differences in TFV‐DP between regimens of the same boosting status (i.e., b/STR vs. b/MTR; u/STR vs. u/MTR) were observed in the full cohort. Future research should examine the clinical utility of these findings in patient‐tailored ART selection. [ABSTRACT FROM AUTHOR]

The cognitive functioning of children who experience intimate partner violence (IPV) has received less attention than their emotional‐behavioral outcomes. Drawing upon data from 615 (48.4% female) 10‐year‐old Australian‐born children and their mothers (9.6% of mothers born in non‐English speaking countries) participating in a community‐based longitudinal study between 2004 and 2016, this study examined the associations between IPV in infancy and cognition in middle childhood (at age 10). Results showed that IPV in the first 12 months of life was associated with lower general cognitive ability and poorer executive attention but not working memory skills. IPV in middle childhood (in the 10th year postpartum) was not associated with cognition. This study provides evidence for the long‐term impact of early life exposure to IPV on children's cognition, and points to the importance of early intervention to optimize development. [ABSTRACT FROM AUTHOR]

Introduction: HIV incidence remains high among African adolescent girls and young women (AGYW). The primary objective of this study is to assess pre‐exposure prophylaxis (PrEP) initiation, use, persistence and HIV acquisition among African AGYW offered PrEP in order to inform PrEP scale‐up. Methods: POWER was a prospective implementation science evaluation of PrEP delivery for sexually active HIV‐negative AGYW ages 16–25 in family planning clinics in Kisumu, Kenya and youth and primary healthcare clinics in Cape Town and Johannesburg, South Africa. Follow‐up visits occurred at month 1 and quarterly for up to 36 months. PrEP users were defined based on the month 1 refill. PrEP persistence through month 6 was assessed using Kaplan–Meier survival analysis among AGYW with a month 1 visit, defining non‐persistence as an ≥15 day gap in PrEP availability for daily dosing. PrEP execution was evaluated in a subset with PrEP supply from the prior visit sufficient for daily dosing by measuring blood tenofovir diphosphate (TFV‐DP) levels. Results: From June 2017 to September 2020, 2550 AGYW were enrolled (1000 in Kisumu, 787 in Cape Town and 763 in Johannesburg). Median age was 21 years, 66% had a sexual partner of unknown HIV status, and 29% had chlamydia and 10% gonorrhoea. Overall, 2397 (94%) initiated PrEP and 749 (31%) had a refill at 1 month. Of AGYW who could reach 6 months of post‐PrEP initiation follow‐up, 128/646 (20%) persisted with PrEP for 6 months and an additional 92/646 (14%) had a gap and restarted PrEP. TFV‐DP levels indicated that 47% (91/193) took an average of ≥4 doses/week. Sixteen HIV seroconversions were observed (incidence 2.2 per 100 person‐years, 95% CI 1.2, 3.5); 13 (81%) seroconverters either did not have PrEP dispensed in the study interval prior to seroconversion or TFV‐DP levels indicated <4 doses/week in the prior 6 weeks. Conclusions: In this study of PrEP integration with primary care and reproductive health services for African AGYW, demand for PrEP was high. Although PrEP use decreased in the first months, an important fraction used PrEP through 6 months. Strategies are needed to simplify PrEP delivery, support adherence and offer long‐acting PrEP options to improve persistence and HIV protection. [ABSTRACT FROM AUTHOR]

The criteria used by physicians to assess alopecia areata severity and its associated burden from the patients' point of view are not well understood. We aimed to understand physician‐assessed determinants of disease severity, factors associated with severity, patient–physician concordance, and patient‐reported burden by severity. Data were drawn from the Adelphi Alopecia Areata Disease Specific Programme™, a point‐in‐time survey of dermatologists and their alopecia areata patients in real‐world practice in Japan conducted between January and March 2021. Patients were categorized into three groups by current disease severity according to physician subjective assessment: mild, moderate, or severe. Demographics, clinical characteristics, and outcomes were described within and compared between the three patient groups. Our study of 97 dermatologists and 587 patients found overall scalp hair loss was the most important factor considered by physicians in determining disease severity. More severe disease was associated with loss of eyebrow hair, eyelashes, and hair loss from other body areas. Agreement on disease severity between physicians and patients was moderate. From the patient perspective, greater severity of alopecia areata was associated with greater anxiety and depression, with lower work productivity and worse quality of life. Our study provides insights into which factors physicians use to determine alopecia areata severity, how physician and patient severity assessments compare, and the burden of alopecia areata on patients. [ABSTRACT FROM AUTHOR]

Aim: To investigate the strength of the independent associations of mathematics performance in children born very preterm (<32wks' gestation or <1500g birthweight) with attending postsecondary education and their current employment status in young adulthood. Method: We harmonized data from six very preterm birth cohorts from five different countries and carried out one‐stage individual participant data meta‐analyses (n=954, 52% female) using mixed effects logistic regression models. Mathematics scores at 8 to 11 years of age were z‐standardized using contemporary cohort‐specific controls. Outcomes included any postsecondary education, and employment/education status in young adulthood. All models were adjusted for year of birth, gestational age, sex, maternal education, and IQ in childhood. Results: Higher mathematics performance in childhood was independently associated with having attended any postsecondary education (odds ratio [OR] per SD increase in mathematics z‐score: 1.36 [95% confidence interval {CI}: 1.03, 1.79]) but not with current employment/education status (OR 1.14 per SD increase [95% CI: 0.87, 1.48]). Interpretation: Among populations born very preterm, childhood mathematics performance is important for adult educational attainment, but not for employment status. [ABSTRACT FROM AUTHOR]

Introduction: On 1 May 2018 Scotland introduced a minimum unit price (MUP) of GB50 pence per unit of alcohol (8 g) sold. We analysed household purchase data to assess the impact of MUP in shifting purchases from higher to lower strength beers. Methods: Data from Kantar Worldpanel's household shopping panel, with 75 376 households and 4.76 million alcohol purchases, 2015–2020. We undertook interrupted time series analyses of the impact of introducing MUP in Scotland on changes in the proportion of the volume of purchased beer with an alcohol by volume (ABV) ≤3.5% using purchases in England as control. We analysed the moderating impact of the volume of purchased beer with an ABV ≤3.5% on the size of the associated impact of MUP in reducing purchases of grams of alcohol within beer. Results: MUP was associated with a relative increase in the proportion of the volume of beer purchased with an ABV ≤3.5%, Scotland minus England, of 10.9% (95% CI 10.6–11.1), following a 43.6% (95% CI 40.1–47.1) increase in the volume of beer purchased with an ABV ≤3.5%, and a 9.6% (95% CI 9.4–9.8) decrease in the volume of beer purchased with an ABV >3.5%. MUP was associated with reduced purchases of grams of alcohol within beer by 8% (95% CI 7.8–8.3), increasing to 9.6% (95% CI 9.3–9.9), when accounting for the moderating impact of shifts to lower strength beer. Discussion and Conclusions: MUP seems an effective policy to reduce off‐trade purchases of alcohol and encourage shifts to lower strength beers. [ABSTRACT FROM AUTHOR]

Introduction: Market research indicates an increasing interest in low‐ and no‐alcohol drinks in Europe, but there is no systematic overview of their availability and consumption. In this article, we present data on the availability and apparent consumption of non‐alcoholic beer in the European Union and the UK. Methods: We use Sold production, exports and imports by PRODCOM list (NACE Rev. 2) dataset, available in Eurostat, to extract the available data on sold production, exports and imports of non‐alcoholic beer in the EU‐27 (total and country‐level) and the UK between 2013 and 2019, and additionally calculate the apparent consumption. Results: Between 2013 and 2019, the sold production volume in the EU increased from 0.59 to 1.38 billion litres, the value from 0.42 to 1.28 billion EUR and value per litre from 0.72 to 0.93 EUR/L. In 2019, the share of non‐alcoholic beer represented 3.8% of all beer volume and 4.1% of all beer value produced. Five countries accounted for 80.8% of sold production volume: Germany, the Netherlands, Spain, Poland and Czechia. The Netherlands and Germany were the largest exporters, while importing was distributed more equally. Per capita, average apparent consumption (2017–2019) was highest in Czechia, followed by the Netherlands, Spain, Luxembourg and Germany. Discussion and Conclusions: Our results show the increasing availability of non‐alcoholic beer in the EU‐27, although overall changes seem to be driven by a small number of countries. More research is needed at the country‐level on no‐ and low‐alcohol consumption trends and drivers, and their impact on alcohol‐related harm reduction. [ABSTRACT FROM AUTHOR]

In Australia, approximately 18% of newborn babies are admitted to a neonatal intensive or special care nursery. While most babies admitted to a neonatal intensive or special care nursery are discharged home within a few weeks, around 6% of babies spend more than 2 weeks in hospital. For the parents of these babies, much of their leave entitlements (Australian Government Paid Parental Leave Scheme is up to18 weeks for the primary care giver and up to 2 weeks for partners) are used before their baby comes home from hospital. The time babies and parents spend together in the early developmental period, during the hospitalisation and when the baby is discharged home, is crucial for optimal child development and bonding. Yet care givers who have a baby admitted to neonatal intensive or special care for extended periods are not currently entitled to any extra parental leave payments in Australia. We recommend the Australian Paid Parental Leave Act is changed to allow primary carers access to 1 week of extra parental leave pay for every week in hospital (for babies admitted to hospital for more than 2 weeks), up to a maximum of 14 weeks. For fathers and partners of these babies, we recommend an additional 2 weeks of extra Dad and Partner Pay. The net cost, taking into account likely productivity benefits, would be less than 1.5% of the current cost of the scheme and would improve health and socio‐economic outcomes for the baby, family and society. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to evaluate daily oral pre‐exposure prophylaxis (PrEP) uptake, retention, and adherence and predictors of study non‐attendance and low PrEP adherence in a Brazilian trans‐specific 48‐week study (PrEParadas). Methods: We enrolled transgender women (TGW) engaging in high‐risk sexual behaviours between August 2017 and December 2018. PrEP adherence was based on tenofovir diphosphate concentrations in dried blood spots (DBS). We used random effects logistic regression models and ordinal models to estimate the odds of having a missed visit and of low PrEP adherence, respectively. Multivariable models were adjusted for variables with p‐value<0.10 in the univariate analysis. Results: From the 271 eligible, 130 participants were enrolled in the study (PrEP uptake: 48%), out of which 111 (85.4%) were retained at 48 weeks. Multivariable model for study non‐attendance included study visit, age, main sexual partner and stimulant use. The odds of missing a visit increased after the week 24. Participants aged 18–24 (adjusted odds ratio [aOR] = 8.76, 95% CI: 2.09–36.7) and 25–34 years (aOR = 6.79, 95% CI: 1.72–26.8) compared to TGW aged 35+ years had significantly higher odds of having a missed visit. The odds of a missed visit were higher among participants reporting stimulant use (aOR = 4.99, 95% CI: 1.37–18.1) compared to no stimulant use. DBS levels at week 48 showed that 42 (38.5%), 14 (12.8%) and 53 (48.6%) of 109 participants had low, moderate and high PrEP adherence. Multivariable model for low PrEP adherence included study visit, age, schooling, race/colour, housing, binge drinking, stimulant use, feminizing hormone therapy (FHT) use and received text message. Low PrEP adherence was significantly higher among participants with less years of schooling (aOR = 6.71, 95% CI: 1.30–34.5) and had a borderline association with Black colour/race (aOR = 6.72, 95% CI: 0.94–47.8). Participants using the FHT available at the site had decreased odds of low PrEP adherence (aOR = 0.38, 95% CI: 0.16–0.88). No participant seroconverted over the course of the study. Conclusions: Although high PrEP retention can be achieved in a gender‐affirming setting, PrEP adherence may be an important challenge faced among TGW due to social disparities. The scale‐up of prevention tools like PrEP will have to address systemic social determinants as these stand as important barriers for TGW's access to health services. [ABSTRACT FROM AUTHOR]

Aim: To assess the causal effect of being born extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g), compared with being born at term, on neurodevelopment and social‐emotional development at 2 years' corrected age. Methods: Prospective geographical cohort study of children born EP/ELBW over 12 months in 2016 from Victoria, Australia, and term‐born controls. Children were assessed at 2 years' corrected age with the Bayley Scales of Infant and Toddler Development–3rd edition and the Infant‐Toddler Social and Emotional Assessment. Delay was defined as <−1 standard deviation relative to the mean of controls. The estimand of interest was the mean difference/odds ratio (OR) between the EP/ELBW and control groups estimated using linear/logistic regression, adjusted for multiple pregnancy and social risk. Results: A total of 205 EP/ELBW and 201 controls were assessed at 2 years. Delay/concerns were more common in the EP/ELBW group compared with controls, for cognitive (OR 3.7 [95% confidence interval 2.3, 6.0]), language (5.3 [3.1, 9.0]) and motor (3.9 [2.3, 6.3]) development, and social‐emotional competence (4.1 [1.6, 10.2]). Conclusion: Being born EP/ELBW has an adverse effect on cognitive, language and motor development, and social‐emotional competence at 2 years' corrected age. Close developmental surveillance, including social‐emotional development, is recommended. [ABSTRACT FROM AUTHOR]

Introduction: Tenofovir diphosphate (TFV‐DP) in dried blood spots (DBS), a measure of cumulative antiretroviral therapy (ART) adherence, is associated with viral suppression and predicts future viremia in persons with HIV (PWH). However, its utility to identify those at risk for virologic failure (VF) and drug resistance is unknown. To address this, we aimed to establish the association between this adherence biomarker and VF with drug resistance in a cohort of PWH initiating first‐line ART in KwaZulu‐Natal, South Africa. Methods: PWH initiating TFV disoproxil fumarate (TDF)‐based ART within a parent prospective cohort were evaluated. Using a nested design, DBS for TFV‐DP were collected from cases who developed VF (HIV‐1 RNA ≥1000 copies/ml) after ≥5 months on ART versus controls, matched 1:2 by site, age, gender, race and ART duration. Cases were categorized as having VF with or without resistance using genotyping. One‐way analysis of variance (ANOVA) was used to compare TFV‐DP for controls, cases with VF and resistance, and cases with VF without resistance. Data are presented as mean (standard deviation, SD) or geometric mean [95% confidence interval, 95% CI]. Results and discussion: One thousand participants were enrolled in the parent study between 2014 and 2016, of which 288 (29%) had DBS available. Of these, 94 (33%) were cases and 194 (67%) were controls; 59% were women. Mean age of our population was 33 (SD 8) years. Genotyping was available in 50 (53%) of the 94 cases. Geometric mean TFV‐DP in DBS from controls was 708 [95% CI; 647–773] fmol/punch, which was higher compared to participants having VF with resistance (n = 36), 386 [95% CI; 241–617] fmol/punch and VF without resistance (n = 14), 61 [95% CI; 22–164] fmol/punch; p<0.001. Genotype could not be obtained in 44 (47%) cases. Conclusions: TFV‐DP in DBS showed a stepwise association with VF and drug resistance in South African PWH. Participants having VF with resistance had mid‐range concentrations of TFV‐DP, which were higher than those for PWH without resistance. Future research on the clinical utility of TFV‐DP concentrations in DBS to predict and prevent the development of VF and drug resistance is needed. [ABSTRACT FROM AUTHOR]

With the introduction of long-acting (LA) injectable antiretrovirals, a new paradigm for HIV prevention and treatment is upon us. Long-acting injectable Cabotegravir: How drug concentrations could help guide patient management May impact the applicability of traditional therapeutic drug monitoring, drug concentration monitoring could help solve patient management issues as CAB-LA use becomes widespread and identify patients at the extremes of drug exposure. [Extracted from the article]

Advances in perinatal medicine in high-income countries have resulted in a significant reduction in mortality for infants born very preterm (<32 weeks gestation), such that most now survive. These results are in line with those from the study by Zayegh et al.1 showing trends in extremely low birthweight outcomes over four decades in Australia were concordant with investigations in later cohorts based on gestational age. Encouragingly, however, once the severity of the very low birth weight or very preterm birth was considered, the use of birthweight or gestational age did not contribute to heterogeneity in the meta-analysis estimates of the cognitive deficit associated with very preterm birth. [Extracted from the article]

Background: Magnesium sulphate was introduced for fetal neuroprotection in Australia in 2010. The aim of this study was to determine how often antenatal magnesium sulphate is used currently and its association with cerebral palsy in children born <28 weeks' gestation. Materials and Methods: Participants comprised all survivors born <28 weeks' gestational age in the state of Victoria in 2016‐17, and earlier, in 1991‐92, 1997, 2005. Rates of cerebral palsy, diagnosed at two years for the 2016‐17 cohort, and at eight years in the earlier cohorts, were compared across eras. Within 2016‐17, the proportions of children exposed to antenatal magnesium sulphate were determined, and rates of cerebral palsy were compared between those with and without exposure to magnesium sulphate. Results: Overall, cerebral palsy was present in 6% (11/171) of survivors born in 2016‐17, compared with 12% (62/499) of survivors born in the three earlier eras (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.25–0.94; P = 0.032). Data were available for 213/215 (99%) survivors born in 2016‐17, of whom 147 (69%) received magnesium sulphate. Data on cerebral palsy at two years were available for 171 (80%) survivors with magnesium data. Cerebral palsy was present in 5/125 (4%) children exposed to magnesium sulphate and in 6/46 (13%) of those not exposed (OR 0.28, 95% CI 0.08–0.96; P = 0.043). Conclusions: Antenatal magnesium sulphate is being translated into clinical practice for infants born <28 weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors. [ABSTRACT FROM AUTHOR]

Background: The highly conserved Grainyhead‐like (Grhl) family of transcription factors play critical roles in the development of the neural tube and craniofacial skeleton. In particular, deletion of family member Grainyhead‐like 2 (Grhl2) leads to mid‐gestational embryonic lethality, maxillary clefting, abdominoschisis, and both cranial and caudal neural tube closure defects. These highly pleiotropic and systemic defects suggest that Grhl2 plays numerous critical developmental roles to ensure correct morphogenesis and patterning. Results: Here, using four separate Cre‐lox conditional deletion models, as well as one genetic epistasis approach (Grhl2+/−;Edn1+/− double heterozygous mice) we have investigated tissue‐specific roles of Grhl2 in embryonic development, with a particular focus on the craniofacial skeleton. We find that loss of Grhl2 in the pharyngeal epithelium (using the ShhCre driver) leads to low‐penetrance micrognathia, whereas deletion of Grhl2 within the ectoderm of the pharynx (NestinCre) leads to small, albeit significant, differences in the proximal‐distal elongation of both the maxilla and mandible. Loss of Grhl2 in endoderm (Sox17‐2aiCre) resulted in noticeable lung defects and a single instance of secondary palatal clefting, although formation of other endoderm‐derived organs such as the stomach, bladder and intestines was not affected. Lastly, deletion of Grhl2 in cells of the neural crest (Wnt1Cre) did not lead to any discernible defects in craniofacial development, and similarly, our epistasis approach did not detect any phenotypic consequences of loss of a single allele of both Grhl2 and Edn1. Conclusion: Taken together, our study identifies a pharyngeal‐epithelium intrinsic, non‐cell‐autonomous role for Grhl2 in the patterning and formation of the craniofacial skeleton, as well as an endoderm‐specific role for Grhl2 in the formation and establishment of the mammalian lung. Key Findings: Deletion of Grhl2 in the Shh‐expressing pharyngeal epithelium leads to low‐penetrance micrognathia.Deletion of Grhl2 in the Sox17‐expressing endoderm leads to subtantial lung formation and cellularity defects, and is incompatible with life.Deletion of Grhl2 in the endoderm of intestine, bladder or other tissues in which Grhl2 expression has been reported does not result in detectable developmental defects. [ABSTRACT FROM AUTHOR]

The urgent global public health need presented by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) has brought scientists from diverse backgrounds together in an unprecedented international effort to rapidly identify interventions. There is a pressing need to apply clinical pharmacology principles and this has already been recognized by several other groups. However, one area that warrants additional specific consideration relates to plasma and tissue protein binding that broadly influences pharmacokinetics and pharmacodynamics. The principles of free drug theory have been forged and applied across drug development but are not currently being routinely applied for SARS‐CoV‐2 antiviral drugs. Consideration of protein binding is of critical importance to candidate selection but requires correct interpretation, in a drug‐specific manner, to avoid either underinterpretation or overinterpretation of its consequences. This paper represents a consensus from international researchers seeking to apply historical knowledge, which has underpinned highly successful antiviral drug development for other viruses, such as HIV and hepatitis C virus for decades. [ABSTRACT FROM AUTHOR]

Introduction: African adolescent girls and young women (AGYW) eligible for HIV pre‐exposure prophylaxis (PrEP) experience high levels of depressive symptoms. Depression can reduce PrEP adherence among adults, although analyses have considered depression as a time‐varying exposure rather than modelling distinct patterns of symptoms. The association between depressive symptoms and PrEP adherence has not been explored for AGYW. To address these gaps, we sought to understand depressive symptom trajectories among African AGYW initiating PrEP and the impact of time‐varying depressive symptoms and symptom trajectories on PrEP adherence. Methods: HPTN 082 was an open‐label PrEP study among AGYW (ages 16 to 24) in Zimbabwe and South Africa from 2016 to 2018. Depressive symptoms were measured at enrolment and Weeks 13, 26 and 52, using the 10‐item Center for Epidemiologic Studies scale; a score ≥10 is indicative of elevated depressive symptoms. PrEP adherence was defined as any detectable tenofovir diphosphate (TFV‐DP) levels. Group‐based trajectory modelling was used to model longitudinal patterns of depressive symptoms. We assessed psychosocial and behavioural predictors of depressive symptom trajectory membership (e.g. PrEP stigma, intimate partner violence [IPV], sexual behaviour). We modelled associations between (1) group trajectory membership and PrEP adherence at Week 52 and (2) time‐varying depressive symptoms and PrEP adherence through follow‐up. Results: At enrolment, 179 (41.9%) participants had elevated depressive symptoms. Group‐based trajectory models revealed persistent elevated depressive symptoms in 48.5%, declining symptoms in 9.4% and no consistent or mild depressive symptoms in 43.3%. AGYW who engaged in transactional sex, reported IPV, or had traumatic stress symptoms were more likely to be assigned to the persistent elevated symptom group compared with the consistent no/mild symptom group (Wald test p‐value all <0.01). Participants assigned to the persistent elevated depressive symptom trajectory had a significantly lower risk of detectable TFV‐DP at Week 52 than those in the no/mild symptom trajectory (adjusted prevalence ratio = 0.89; 95% CI: 0.80 to 0.98). Elevated depressive symptoms were significantly inversely associated with PrEP use throughout follow‐up (adjusted relative risk = 0.73; 95% CI = 0.53 to 0.99). Conclusions: Persistent depressive symptoms were common among African AGYW seeking PrEP. Integration of depressive symptom screening and treatment into PrEP programmes may improve PrEP effectiveness among African women. [ABSTRACT FROM AUTHOR]

Background: Of all newborns, 1%‐2% are born very preterm (VP; <32 weeks) or with very low birthweight (VLBW; ≤1500 g). Advances in prenatal and neonatal care have substantially improved their survival, and the first generations who have benefited from these advances are now entering middle age. While most lead healthy lives, on average these adults are characterised by a number of adversities. These include cardiometabolic risk factors, airway obstruction, less physical activity, poorer visual function, lower cognitive performance, and a behavioural phenotype that includes inattention and internalising and socially withdrawn behaviour that may affect life chances and quality of life. Outcomes in later adulthood are largely unknown, and identifying trajectories of risk or resilience is essential in developing targeted interventions. Joint analyses of data and maintenance of follow‐up of cohorts entering adulthood are essential. Such analyses are ongoing within the Adults Born Preterm International Collaboration (APIC; www.apic-preterm.org). Joint analyses require data harmonisation, highlighting the importance of consistent assessment methodologies. Objective: To present an expert recommendation on Common Core Assessments to be used in follow‐up assessments of adults born preterm. Methods: Principles of Common Core Assessments were discussed at APIC meetings. Experts for each specific outcome domain wrote the first draft on assessments pertaining to that outcome. These drafts were combined and reviewed by all authors. Consensus was reached by discussion at APIC meetings. Results: We present a recommendation by APIC experts on consistent measures to be used in adult follow‐up assessments. Conclusions: The recommendation encompasses both "core" measures which we recommend to use in all assessments of adults born preterm that include the particular outcome. This will allow comparability between time and location. The recommendation also lists optional measures, focusing on current gaps in knowledge. It includes sections on study design, cardiometabolic and related biomarkers, biological samples, life style, respiratory, ophthalmic, cognitive, mental health, personality, quality of life, sociodemographics, social relationships, and reproduction. [ABSTRACT FROM AUTHOR]

Introduction: Randomized trials of new agents for HIV pre‐exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well‐characterized adherence‐efficacy relationship for F/TDF to back‐calculate the (non‐PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV). Methods: The DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non‐inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV‐DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV. Results: There were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person‐years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV‐negative controls, 5% of the person‐time years had low, 9% had medium and 86% had high TFV‐DP levels. A non‐informative prior distribution for counterfactual bHIV, combined with the prior for TFV‐DP level‐efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV. Conclusions: Based on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non‐PrEP control group in randomized, active‐controlled PrEP trials that include a F/TDF‐comparator group. [ABSTRACT FROM AUTHOR]

Introduction: Event‐driven pre‐exposure prophylaxis (edPrEP) with oral tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective for preventing HIV acquisition in men who have sex with men (MSM) and is preferred over daily PrEP by some MSM. However, it is largely unknown how well MSM adhere to edPrEP. We then aimed to assess PrEP protection during CAS among MSM using edPrEP and participating in the Amsterdam PrEP demonstration project (AMPrEP). Methods: We analysed data from participants enrolled in AMPrEP who were taking edPrEP. We measured adherence through (1) a mobile application in which sexual behaviour and PrEP‐use were recorded daily, (2) three‐monthly self‐completed questionnaires and (3) dried blood spot (DBS) samples collected around six, twelve and twenty‐four months after PrEP initiation. We assessed the proportion of days with condomless anal sex (CAS) acts that were protected by PrEP, per partner type (i.e. steady partners, known casual partners, unknown casual partners), and the proportion of three‐month periods during which PrEP was correctly used. Intracellular TFV‐diphosphate (TFV‐DP) concentrations were determined from DBS. Good adherence was defined as at least one tablet before and one tablet within 48 hours after a CAS act. Results: Between 11 September 2015 and 6 October 2019, 182 of 376 MSM (48.4%) used edPrEP for at least one three‐month period. Of the 8224 CAS days that were reported in the app during edPrEP‐use, we observed good protection for most CAS days involving steady partners (n = 1625/2455, 66.9%), known casual partners (n = 3216/3472, 92.6%) and unknown casual partners (n = 2074/2297, 90.3%). Men reported consistently correct PrEP‐use in 851 (81.4%) of the 1046 three‐month periods of edPrEP‐use. The median TFV‐DP concentration was 591 fmol/sample (interquartile range = 270 to 896). Conclusions: Adherence to edPrEP was high as determined from the online app and questionnaire. DBS measurements were consistent with two to three tablets per week on average. [ABSTRACT FROM AUTHOR]

Study Objective: To assess the association between tenofovir diphosphate (TFV‐DP) in dried blood spots (DBS), a measure of cumulative tenofovir‐based antiretroviral (ART) adherence, with medication regimen complexity in persons with human immunodeficiency virus (PWH). Design: Prospective clinical cohort (up to three visits over 48 weeks). Setting: Academic‐based HIV clinic. Patients: PWH receiving tenofovir disoproxil fumarate (TDF)‐based ART. Measurements: DBS for TFV‐DP were collected at every study visit. Baseline patient‐level medication regimen complexity index (pMRCI) scores were calculated and categorized into three sub‐scores (disease‐specific [ART], non‐ART, and over‐the‐counter [OTC]). The pMRCI scores were evaluated to assess the association with TFV‐DP in DBS <350 fmol/punch after adjusting for clinical covariates. pMRCI scores were also categorized to estimate the adjusted relative risk (aRR) of having a TFV‐DP <350 fmol/punch between pMRCI quartiles. Main Results: Data from 525 participants (1,146 person‐visits) were analyzed. Baseline median (interquartile range [IQR]) pMRCI scores for participants with TFV‐DP in DBS <350 vs. ≥350 fmol/punch were 4 (3, 8) vs. 4 (2, 6) for ART, 27 (12, 31) vs. 12 (5, 22) for non‐ART, and 0 (0, 1) vs. 0 (0, 2) for OTC, respectively. For the non‐ART scores, the aRR for having a TFV‐DP in DBS <350 fmol/punch was 6.4 (95% CI: 2.0, 20.6; P=0.002) when comparing participants in the highest pMRCI quartile with those in the lowest quartile. Conclusions: Higher pMRCI for non‐ART medications is associated with lower adherence as measured by TFV‐DP in DBS. Future research should investigate whether reducing non‐ART medication complexity improves ART adherence and exposure in PWH. [ABSTRACT FROM AUTHOR]

Plants' defenses against herbivores usually include both resistance and tolerance mechanisms. Their deployment has predominantly been studied in either single‐plant genotypes or multiple genotypes exposed to single herbivores. In natural situations, however, most plants are attacked by multiple herbivores. Therefore, aims of this study were to assess and compare the effects of single and multiple herbivores on plant resistance and tolerance traits, and the consequences for overall plant performance. For this, we exposed multiple genotypes of wild woodland strawberry (Fragaria vesca) to jasmonic acid (JA), to mimic chewing herbivory and induce the plants' defense responses, and then introduced the generalist herbivore Spodoptera littoralis to feed on them. We found that woodland strawberry consistently showed resistance to S. littoralis herbivory, with no significant genetic variation between the genotypes. By contrast, the studied genotypes showed high variation in tolerance, suggesting evolutionary potential in this trait. Prior JA application did not alter these patterns, although it induced an even higher level of resistance in all tested genotypes. The study provides novel information that may be useful for breeders seeking to exploit tolerance and resistance mechanisms to improve strawberry crops' viability and yields, particularly when multiple herbivores pose significant threats. [ABSTRACT FROM AUTHOR]

Introduction: The antenatal diagnosis of sagittal craniosynostosis can be challenging, but there are several published papers describing a traumatic outcome to both the affected fetus and the mother during delivery of a scaphocephalic child. The antenatal imaging from affected children was collected along with the mother's obstetric history. The aim of this study was to identify antenatal ultrasound features that may assist the diagnosis of sagittal synostosis before birth, to enable appropriate delivery planning and avoid both maternal and fetal trauma during birth.Methods: Antenatal ultrasound scans in both the second and third trimesters were traced for 36 children with sagittal synostosis. The initially diagnostic CT scans were also sourced. A delivery history was collected from the hospital case notes where available.Results: The affected group showed a statistically significant reduction in cephalic index during the second half of pregnancy compared with the normal population which became slightly more brachycephalic (P = 0.001). Regression analysis showed an average reduction in cephalic index of 0.57 units per month. There was also a much higher rate of malpresentation and surgical deliveries in the affected group than the normal population. There was a relationship between sagittal craniosynostosis and breech presentation and an associated higher rate of surgical deliveries.Conclusion: It is possible to detect sagittal synostosis in the third trimester of pregnancy which may assist with delivery planning. [ABSTRACT FROM AUTHOR]

In dry conditions, tall and fast‐growing wheat plants with good tolerance to drought may offer higher grain yields than 'Green revolution' wheat. [ABSTRACT FROM AUTHOR]

Brain atlases providing standardised identification of neonatal brain regions are key in investigating neurological disorders of early childhood. Our previously developed Melbourne Children's Regional Infant Brain (M‐CRIB) and M‐CRIB 2.0 neonatal brain atlases provide standardised parcellation of 100 brain regions including cortical, subcortical, and cerebellar regions. The aim of this study was to extend M‐CRIB atlas coverage to include 54 white matter (WM) regions. Participants were 10 healthy term‐born neonates that were used to create the initial M‐CRIB atlas. WM regions were manually segmented based on T2 images and co‐registered diffusion tensor imaging‐based, direction‐encoded colour maps. Our labelled regions imitate the Johns Hopkins University neonatal atlas, with minor anatomical modifications. All segmentations were reviewed and approved by a paediatric radiologist and a neurosurgery research fellow for anatomical accuracy. The resulting neonatal WM atlas comprises 54 WM regions: 24 paired regions, and six unpaired regions comprising five corpus callosum subdivisions, and one pontine crossing tract. Detailed protocols for manual WM parcellations are provided, and the M‐CRIB‐WM atlas is presented together with the existing M‐CRIB cortical, subcortical, and cerebellar parcellations in 10 individual neonatal MRI data sets. The novel M‐CRIB‐WM atlas, along with the M‐CRIB cortical and subcortical atlases, provide neonatal whole brain MRI coverage in the first multi‐subject manually parcellated neonatal atlas compatible with atlases commonly used at older time points. The M‐CRIB‐WM atlas is publicly available, providing a valuable tool that will help facilitate neuroimaging research into neonatal brain development in both healthy and diseased states. [ABSTRACT FROM AUTHOR]

In a randomized, crossover pharmacokinetic study in healthy volunteers (N = 14), a single dose of 2 g probenecid (PRO)‐boosted 600 mg tenofovir disoproxil fumarate (TDF)/400 mg emtricitabine (FTC) (test (T) +PRO) was compared with the current on‐demand HIV preexposure prophylaxis from the IPERGAY study (a 600 mg TDF/400 mg FTC on day 1 and 300 mg TDF/200 mg FTC on days 2 and 3) (control, C IPERGAY). PRO increased mean single‐dose area under the plasma concentration‐time curve extrapolated to infinity (AUC0–∞,SD) of tenofovir (TFV) and FTC by 61% and 68%, respectively. The TFV‐diphosphate (TFV‐DP) concentrations in peripheral blood mononuclear cells were higher (~30%) at 24 hours in T +PRO but then fell significantly lower (~40%) at 72 hours compared with C IPERGAY. The interaction between FTC and PRO was unexpected and novel. Further study is needed to determine if this PRO‐boosted TDF/FTC regimen would be clinically effective. [ABSTRACT FROM AUTHOR]

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety‐one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45‐min sessions, 5 days a week over 5–7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task‐based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level‐dependent (BOLD) signal during an n‐back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n‐back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group‐by‐time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training‐induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831. [ABSTRACT FROM AUTHOR]

Aim: Brain alterations in very preterm children at risk for developmental coordination disorder were investigated.Methods: Infants born very preterm with gestation age <30 weeks or birthweight <1250 g were recruited from Royal Women's Hospital Melbourne from 2001 to 2003. Volumetric imaging was performed at term equivalent age; at seven years, volumetric imaging and diffusion tensor imaging were performed. At seven years, 53 of 162 children without cerebral palsy had scores ≤16th percentile on the Movement Assessment Battery for Children-Second Edition and were considered at risk for developmental coordination disorder.Results: At term equivalent age, smaller brain volumes were found for total brain tissue, cortical grey matter, cerebellum, caudate accumbens, pallidum and thalamus in children at risk for developmental coordination disorder (p < 0.05); similar patterns were present at seven years. There was no evidence for catch-up brain growth in at-risk children. At seven years, at-risk children displayed altered microstructural organisation in many white matter tracts (p < 0.05).Conclusion: Infants born very preterm at risk for developmental coordination disorder displayed smaller brain volumes at term equivalent age and seven years, and altered white matter microstructure at seven years, particularly in motor areas. There was no catch-up growth from infancy to seven years. [ABSTRACT FROM AUTHOR]

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The article highlights several pharmacological methods of adherence assessment in HIV Prevention. topics including use of Tenofovir (TFV) disoproxil fumarate (TDF) with emtricitabine (FTC) an oral fixed dose combination tablet for HIV pre-exposure prophylaxis (PrEP); recent dosing markers like plasma testing, Urine analysis, and FTC concentrations in saliva; and cumulative dosing markers like TFV-diphosphate in peripheral blood mononuclear cell and dried blood spots and hair growth matrix.

Drug‐drug interactions have been demonstrated to alter cytochrome 2D6 (CYP2D6) enzyme phenotype due to inhibitor ingestion, although it is unclear how substrate interactions affect phenotype. This was a pragmatic clinical trial examining the kinetics of a CYP2D6 enzyme probe drug with and without CYP2D6‐dependent substrates. Patients were enrolled into an inpatient study unit, and orally administered a 2 mg microdose of dextromethorphan (DM) to probe enzyme activity with and without CYP2D6‐dependent drug‐drug interactions. Thirty‐nine subjects were enrolled in this trial. Twelve subjects were on no CYP2D6‐dependent drugs and 27 were on one or more CYP2D6‐dependent drugs. There were 1 poor metabolizer, 5 intermediate metabolizers, 31 normal metabolizers, and 2 ultra‐rapid metabolizers. Those with co‐ingestion of another CYP2D6‐dependent drug were 9.49 (95% confidence interval (CI): 1.54–186.41; P = 0.01) times more likely to have genotype‐phenotype discordance based upon the 3 hours dextrophan/dextromethorphan (DX/DM) ratio. CYP2D6 substrate co‐ingestions can cause genotype‐phenotype discordance. [ABSTRACT FROM AUTHOR]