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We examined the relationships between high school CTE participation and indicators of career and college readiness using 2009 High School Longitudinal Study restricted-use data. Regression analyses of 2009-2018 data revealed significantly lower dropout rates for CTE participants, but only White CTE participants experienced better employment likelihood. CTE participants were mostly employed in service or manual labor occupations with below average wages and were significantly less likely to attend a 4-year college. CTE benefits were disproportionate by race and gender, and participation may have a "cooling out" effect on the aspirations of some students. Advising and urban education implications are discussed.

Great interest exists in developing a transgenic trait that controls the economically important soybean (Glycine max) pest, soybean cyst nematode (SCN, Heterodera glycines), due to its adaptation to native resistance. Soybean plants expressing the Bacillus thuringiensis delta-endotoxin, Cry14Ab, were recently demonstrated to control SCN in both growth chamber and field testing. In that communication, ingestion of the Cry14Ab toxin by SCN second stage juveniles (J2s) was demonstrated using fluorescently labeled Cry14Ab in an in vitro assay. Here, we show that consistent with expectations for a Cry toxin, Cry14Ab has a mode of action unique from the native resistance sources Peking and PI 88788. Further, we demonstrate in planta the ingestion and localization of the Cry14Ab toxin in the midgut of nematodes feeding on roots expressing Cry14Ab using immunogold labeling and transmission electron microscopy. We observed immunolocalization of the toxin and resulting intestinal damage primarily in the microvillus-like structure (MvL)-containing region of the midgut intestine but not in nematodes feeding on roots lacking toxin. This demonstrated that Cry14Ab was taken up by the J2 SCN, presumably through the feeding tube within the plant root cell that serves as its feeding site. This suggests that relatively large proteins can be taken up through the feeding tube. Electron microscopy showed that Cry14Ab caused lysis of the midgut MvL membrane and eventual degradation of the MvL and the lysate, forming particulate aggregates. The accumulated electron-dense aggregate in the posterior midgut intestine was not observed in SCN in nonCry14Ab-expressing plants. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Little systematic attention has been paid toward belonging for young children, particularly in contexts of diversity that are regularly part of school settings. Two-Way immersion (TWI) programs provide one educational context ideally suited for exploring the constructs of belonging and inclusion in linguistically and culturally diverse settings. This study explores how kindergarteners articulate a sense of belonging in a socio-linguistically diverse international Two-Way immersion school. Focus groups were conducted with kindergarteners about what they would need to fit in and belong. Findings reveal that these kindergarteners recognize the utility of language but do not segregate peers by language group. Language proficiencies were articulated as a procedure for being able to 'do school.' They appear to experience language diversity as a 'de facto' context and something to manage procedurally. Comments on friendship-making also express the importance of conforming to concrete social interpersonal norms; friendship as compliance to social norms and procedures of asking someone to be your friend and being nice. A consideration of inclusion as the negotiation of belonging in this diverse context allows us to consider the specific ideas and solutions of these kindergarteners as a shared project of belonging in which they all work to enact inclusion.

Intercultural competence (IC), a desired outcome in many international schools, comprises the necessary knowledge, skills, and attitudes to effectively navigate intercultural situations. However, international schools are often elite institutions catering to affluent expatriates and host country nationals, thus aligning the development of IC to elite norms. This study explored the perspectives of six local scholarship students in a Central American international school, finding that these students have internalised this elitism as part of their IC development. This suggests that international schools could better serve the broader community by incorporating a critical stance towards IC that promotes equity without reinforcing elitism.

Abstract Variations in physical activity energy expenditure can make accurate prediction of total energy expenditure (TEE) challenging. The purpose of the present study was to determine the accuracy of available equations to predict TEE in individuals varying in physical activity (PA) levels. TEE was measured by DLW in 56 adults varying in PA levels which were monitored by accelerometry. Ten different models were used to predict TEE and their accuracy and precision were evaluated, considering the effect of sex and PA. The models generally underestimated the TEE in this population. An equation published by Plucker was the most accurate in predicting the TEE in our entire sample. The Pontzer and Vinken models were the most accurate for those with lower PA levels. Despite the levels of accuracy of some equations, there were sizable errors (low precision) at an individual level. Future studies are needed to develop and validate these equations.

Abstract A major challenge to achieving industry-scale biomanufacturing of therapeutic alkaloids is the slow process of biocatalyst engineering. Amaryllidaceae alkaloids, such as the Alzheimer’s medication galantamine, are complex plant secondary metabolites with recognized therapeutic value. Due to their difficult synthesis they are regularly sourced by extraction and purification from the low-yielding daffodil Narcissus pseudonarcissus. Here, we propose an efficient biosensor-machine learning technology stack for biocatalyst development, which we apply to engineer an Amaryllidaceae enzyme in Escherichia coli. Directed evolution is used to develop a highly sensitive (EC50 = 20 μM) and specific biosensor for the key Amaryllidaceae alkaloid branchpoint 4’-O-methylnorbelladine. A structure-based residual neural network (MutComputeX) is subsequently developed and used to generate activity-enriched variants of a plant methyltransferase, which are rapidly screened with the biosensor. Functional enzyme variants are identified that yield a 60% improvement in product titer, 2-fold higher catalytic activity, and 3-fold lower off-product regioisomer formation. A solved crystal structure elucidates the mechanism behind key beneficial mutations.

Museum occurrence records are popular sources of information for creating Environmental Niche Models (ENMs), which allow the mapping of the potential niche ranges of species. Occurrence data is often downloaded en masse from established databases. However, the use of non-traditional data sources, such as occurrence records from community/citizen science outreach and social media, is increasing in use and abundance. Data from non-traditional data sources are potentially valuable records of information, particularly for species where museum occurrence records may be comparatively scarce. In the current study, we aimed to determine the impact of adding occurrence data from non-traditional databases to ENMs that were originally created using traditional databases with a group of comparatively understudied species, native Australian bees. We used the Maxent algorithm to model the potential environmental niches of eight species. We created three models for each species: 1) one consisting of only location data from museum specimen collection records from the Atlas of Living Australia (ALA) (a traditional database), 2) one combining ALA and geo-tagged social media (Flickr) data, and 3) a model combining ALA and geo-tagged community science data from iNaturalist. This resulted in 24 different models. By comparing the models produced from each of the augmented data sets with the traditional species data set (ALA vs. ALA & Flickr; ALA vs. ALA & iNaturalist) we showed that there were significant differences, not only in predicted ranges, but also in the weighting of environmental variables used by the models to predict the environmental niche. Differences were more greatly influenced by the geographic location of the extra occurrences rather than the number of additional occurrence points. We demonstrate the potential value and risks of including social media and community science geo-tagged image data in supplementing knowledge of species distributions, particularly for relatively under-sampled species such as native bees.

Understanding the density-dependent impacts of an invasive predator is integral for predicting potential consequences for prey populations. Functional response experiments are used to assess the rate of prey consumption and a predator’s ability to search for and consume prey at different resource densities. However, results can be highly context-dependent, limiting their extrapolation to natural ecosystems. Here, we examined how simulated habitat complexity, through the addition of substrate in which prey can escape predation, affects the functional response of invasive European green crabs (Carcinus maenas) foraging on two different bivalve species. Green crabs feeding on varnish clams (Nuttallia obscurata) shifted from a Type II hyperbolic functional response in the absence of substrate to density-independent consumption when prey could bury. Green crabs ate few Japanese littleneck clams (Venerupis philippinarum) under all densities, such that no functional response curve of any type could be produced and their total consumption was always density independent. However, the probability of at least one Japanese littleneck clam being consumed increased significantly with initial clam density and crab claw size across all treatments. At mean crab claw size and compared to trials without substrate, the proportion of varnish clams consumed were 4.2 times smaller when substrate was present, but substrate had a negligible effect (1.2 times) on Japanese littlenecks. The proportion of varnish clams consumed increased with crab claw size and were higher across both substrate conditions than the proportion of Japanese littlenecks consumed; however, the proportion of Japanese littleneck clams consumed increased faster with claw size than that of varnish clams. Our results suggest that including environmental features and variation in prey species can influence the density-dependent foraging described by functional response experiments. Incorporating replicable features of the natural environment into functional response experiments is imperative to make more accurate predictions about the impact of invasive predators on prey populations.

Objective This research was conducted to evaluate the effects of citrus fiber (CF) as a natural alternative to sodium tripolyphosphate (STPP) in marinated broiler boneless chicken breast and inside beef skirt on overall retention rate, shear force, and consumer sensory attributes. Methods Five different marinade formulations were targeted to include 0.9% salt, either 0.25% or 0.50% STPP or CF and water on a finished product basis. Water and salt only were considered the negative control (CON). Chicken breasts (n = 14) and inside beef skirt (n = 14) were randomly assigned to a treatment, raw weights recorded and then placed in a vacuum tumbler. Marinated weights were recorded, individually packed, and randomly assigned to either retail display for 10-day retention rate, shear force analysis, cook loss, or consumer sensory panel. Results Pickup percentage, and overall retention was similar among treatments for chicken breast and inside beef skirt. Citrus fiber treatments resulted in higher cooking loss compared to the CON in chicken breast; though, CF050 resulted in similar cooking loss compared to STPP025 in inside beef skirt. No differences were found in sensory attributes for chicken breast, however, WBSF data showed CF025 was tougher than CF050, STPP050, and CON. Inside beef skirt with CF050 were least liked overall by the consumer panel. Conclusion Citrus fiber included in marinades at a lower percentage rate can produce similar texture characteristics, and sensory properties compared with those marinated with STPP.

Background: Dementia is one of the most common and serious disorders in later life and the economic and personal cost of caring for people with dementia is immense. There is a need to be able to evaluate interventions in dementia using cost-effectiveness analyses, but the generic preference-based measures typically used to measure effectiveness do not work well in dementia. Existing dementia-specific measures can effectively measure health-related quality of life but in their current form cannot be used directly to inform cost-effectiveness analysis using quality-adjusted life-years as the measure of effectiveness. Objectives: The aim was to develop two brief health-state classifications, one from DEMQOL and one from DEMQOL-Proxy, to generate health states amenable to valuation. These classification systems consisted of items taken from DEMQOL and DEMQOL-Proxy so they can be derived from any study that has used these instruments. Data sources: In the first stage of the study we used a large, clinically representative sample aggregated from two sources: a sample of patients and carers attending a memory service in south London and a sample of patients and carers from other community services in south London. This included 644 people with a diagnosis of mild/moderate dementia and 689 carers of those with mild/moderate dementia. For the valuation study, the general population sample of 600 respondents was drawn to be representative of the UK general population. Households were sampled in urban and rural areas in northern England and balanced to the UK population according to geodemographic profiles. In the patient/carer valuation study we interviewed a sample of 71 people with mild dementia and 71 family carers drawn from a memory service in south London. Finally, the instruments derived were applied to data from the HTA-SADD (Study of Antidepressants for Depression in Dementia) trial. Review methods: This was a complex multiphase study with four linked phases: phase 1 – derivation of the health-state classification system; phase 2 – general population valuation survey and modelling to produce values for every health state; phase 3 – patient/carer valuation survey; and phase 4 – application of measures to trial data. Results: All four phases were successful and this report details this development process leading to the first condition-specific preference-based measures in dementia, an important new development in this field. Limitations: The first limitation relates to the lack of an external data set to validate the DEMQOL-U and DEMQOL-Proxy-U classification systems. Throughout the development process we have made decisions about which methodology to use. There are other valid techniques that could be used and it is possible to criticise the choices that we have made. It is also possible that the use of a mild to moderate dementia sample has resulted in classification systems that do not fully reflect the challenges of severe dementia. Conclusion: The results presented are sufficiently encouraging to recommend that the DEMQOL instruments be used alongside a generic measure such as the European Quality of Life-5 Dimensions (EQ- 5D) in future studies of interventions in dementia as there was evidence that they can be more sensitive for patients at the milder end of disease and some limited evidence that the person with dementia measure may be able to reflect deterioration. Funding: The National Institute for Health Research Health Technology Assessment programme.

Avian paramyxovirus type 1 (APMV-1) is a virus of birds that results in a range of outcomes, from asymptomatic infections to outbreaks of systemic respiratory and neurologic disease, depending on the virus strain and the avian species affected. Humans are rarely affected; those who are predominantly experience mild conjunctivitis. We report a fatal case of neurologic disease in a 2-year-old immunocompromised child in Australia. Metagenomic sequencing and histopathology identified the causative agent as the pigeon variant of APMV-1. This diagnosis should be considered in neurologic conditions of undefined etiologies. Agnostic metagenomic sequencing methods are useful in such settings to direct diagnostic and therapeutic efforts.

Sociocultural competence is the third goal of TWI programs, yet there is a lack of consensus on what it looks like in terms of student outcomes in the classroom. As an inherently social construct, sociocultural competence leads to successful interactions with people who are different from each other along various dimensions. Sociocultural competence in TWI classrooms, specifically, may manifest in successful friendship formation among students across different language and cultural groups. We use Social Network Analysis to investigate a friendship network in one TWI kindergarten classroom in Costa Rica using a measure of "homophily" - the tendency for people to create ties with people who are similar to themselves. Findings from the data in this study reveal patterns of friendship that indicate higher levels of sociocultural competence for bilingual students, both individually and as a group, in that they more regularly establish friendships across language groups in their classroom (showing less homophily) than do English or Spanish dominant students. A major contribution of this paper is to show how social network theory can be leveraged to help better specify and measure sociocultural competence in the TWI classroom by looking across different levels of analyses.

Objective: To determine the accuracy, acceptability and cost-effectiveness of polymerase chain reaction (PCR) and optical immunoassay (OIA) rapid tests for maternal group B streptococcal (GBS) colonisation at labour. Design: A test accuracy study was used to determine the accuracy of rapid tests for GBS colonisation of women in labour. Acceptability of testing to participants was evaluated through a questionnaire administered after delivery, and acceptability to staff through focus groups. A decision-analytic model was constructed to assess the cost-effectiveness of various screening strategies. Setting: Two large obstetric units in the UK. Participants: Women booked for delivery at the participating units other than those electing for a Caesarean delivery. Interventions: Vaginal and rectal swabs were obtained at the onset of labour and the results of vaginal and rectal PCR and OIA (index) tests were compared with the reference standard of enriched culture of combined vaginal and rectal swabs. Main outcome measures: The accuracy of the index tests, the relative accuracies of tests on vaginal and rectal swabs and whether test accuracy varied according to the presence or absence of maternal risk factors. Results: PCR was significantly more accurate than OIA for the detection of maternal GBS colonisation. Combined vaginal or rectal swab index tests were more sensitive than either test considered individually [combined swab sensitivity for PCR 84% (95% CI 79–88%); vaginal swab 58% (52–64%); rectal swab 71% (66–76%)]. The highest sensitivity for PCR came at the cost of lower specificity [combined specificity 87% (95% CI 85–89%); vaginal swab 92% (90–94%); rectal swab 92% (90–93%)]. The sensitivity and specificity of rapid tests varied according to the presence or absence of maternal risk factors, but not consistently. PCR results were determinants of neonatal GBS colonisation, but maternal risk factors were not. Overall levels of acceptability for rapid testing amongst participants were high. Vaginal swabs were more acceptable than rectal swabs. South Asian women were least likely to have participated in the study and were less happy with the sampling procedure and with the prospect of rapid testing as part of routine care. Midwives were generally positive towards rapid testing but had concerns that it might lead to overtreatment and unnecessary interference in births. Modelling analysis revealed that the most cost-effective strategy was to provide routine intravenous antibiotic prophylaxis (IAP) to all women without screening. Removing this strategy, which is unlikely to be acceptable to most women and midwives, resulted in screening, based on a culture test at 35–37 weeks’ gestation, with the provision of antibiotics to all women who screened positive being most cost-effective, assuming that all women in premature labour would receive IAP. The results were sensitive to very small increases in costs and changes in other assumptions. Screening using a rapid test was not cost-effective based on its current sensitivity, specificity and cost. Conclusions: Neither rapid test was sufficiently accurate to recommend it for routine use in clinical practice. IAP directed by screening with enriched culture at 35–37 weeks’ gestation is likely to be the most acceptable cost-effective strategy, although it is premature to suggest the implementation of this strategy at present.

Summary: Visual illusions are errors in signal perception and inform us about the visual and cognitive processes of different animals. Invertebrates are relatively less studied for their illusionary perception, despite the insight that comparative data provides on the evolution of common perceptual mechanisms. The Solitaire Illusion is a numerosity illusion where a viewer typically misperceives the relative quantities of two items of different colors consisting of identical quantity, with more centrally clustered items appearing more numerous. We trained European honeybees (Apis mellifera) and European wasps (Vespula vulgaris) to select stimuli containing a higher quantity of yellow dots in arrays of blue and yellow dots and then presented them with the Solitaire Illusion. Insects learnt to discriminate between dot quantities and showed evidence of perceiving the Solitaire Illusion. Further work should determine whether the illusion is caused by numerical cues only or by both quantity and non-numerical spatial cues.

Objectives: To describe the epidemiology and impact of Omicron BR.2.1, an emergent SARS-CoV-2 Omicron BA.2.75 sublineage displaying high fitness compared to other cocirculating subvariants in New South Wales, Australia. Methods: From September 01 to November 26, 2022, 4971 SARS-CoV-2 consensus genomes from unique patients were generated, and correlated with international travel and reinfection history, and admission to the intensive care unit. Results: BR.2.1 became the predominant variant by late November, and was responsible for a significantly higher proportion of community-acquired cases during the study period (55.1% vs 38.4%, P < 0.001). Reinfections (defined as occurring between 6 and 24 weeks after a prior diagnosis of COVID-19) were significantly higher among BR.2.1 compared to non-BR.2.1 infected persons (17.0% vs 6.0%, P < 0.001). BR.2.1 cases were also significantly younger compared to non-BR.2.1 (median age 48 years (interquartile range [IQR] 32) vs 53 years (IQR 32), P = 0.004). The proportion of patients admitted to the intensive care unit with BR.2.1 was not significantly higher than other subvariants (2.3% vs 2.0%, P = 0.717). Conclusion: Having emerged locally within New South Wales, BR.2.1 caused a significant number of SARS-CoV-2 reinfections, but with disease severity comparable with other currently circulating lineages. Given its rapid rise in prevalence, BR.2.1 has the potential to become established internationally.

Recent events concerning jet fuel contamination of drinking water have shown that we need a better understanding of the effects of ingested jet fuel. To this end, a reproductive study with ingested jet fuel in rats was undertaken with relatively high concentrations of Jet Propellant (JP)-5 along with a human estrogen receptor activation in vitro assay using JP-5, JP-8, and an alternative jet fuel derived from the camelina plant referred to as HydroRenewable Jet (HRJ) fuel, to help evaluate potential effects of ingested jet fuel. The results of the in vivo study provide evidence that JP-5 can act as an endocrine disruptor, with specific observations including altered hormone levels with JP-5 exposure (significantly lower estradiol levels in male rats and significantly increased Dehydroepiandrosterone levels in females), and a decreased male/female offspring ratio. The in vitro hormone receptor activation assay indicated that JP-5 and JP-8 are capable of upregulating human estrogen receptor (ER) activity, while HRJ was not active in the ER assay. The jet fuels were not able to activate androgen or glucocorticoid receptors in further in vitro assays. These results infer potential endocrine disruption associated with JP-5, with activation of the estrogen receptor as one potential mechanism of action.

Towards the end of June 2021, temperature records were broken by several degrees Celsius in several cities in the Pacific Northwest areas of the US and Canada, leading to spikes in sudden deaths and sharp increases in emergency calls and hospital visits for heat-related illnesses. Here we present a multi-model, multi-method attribution analysis to investigate the extent to which human-induced climate change has influenced the probability and intensity of extreme heat waves in this region. Based on observations, modelling and a classical statistical approach, the occurrence of a heat wave defined as the maximum daily temperature (TXx) observed in the area 45–52∘ N, 119–123∘ W, was found to be virtually impossible without human-caused climate change. The observed temperatures were so extreme that they lay far outside the range of historical temperature observations. This makes it hard to state with confidence how rare the event was. Using a statistical analysis that assumes that the heat wave is part of the same distribution as previous heat waves in this region led to a first-order estimation of the event frequency of the order of once in 1000 years under current climate conditions. Using this assumption and combining the results from the analysis of climate models and weather observations, we found that such a heat wave event would be at least 150 times less common without human-induced climate change. Also, this heat wave was about 2 ∘C hotter than a 1-in-1000-year heat wave would have been in 1850–1900, when global mean temperatures were 1.2 ∘C cooler than today. Looking into the future, in a world with 2 ∘C of global warming (0.8 ∘C warmer than today), a 1000-year event would be another degree hotter. Our results provide a strong warning: our rapidly warming climate is bringing us into uncharted territory with significant consequences for health, well-being and livelihoods. Adaptation and mitigation are urgently needed to prepare societies for a very different future.

IntroductionDelayed puberty (DP) is a frequent concern for adolescents. The most common underlying aetiology is self-limited DP (SLDP). However, this can be difficult to differentiate from the more severe condition congenital hypogonadotrophic hypogonadism (HH), especially on first presentation of an adolescent patient with DP. This study sought to elucidate phenotypic differences between the two diagnoses, in order to optimise patient management and pubertal development.MethodsThis was a study of a UK DP cohort managed 2015-2023, identified through the NIHR clinical research network. Patients were followed longitudinally until adulthood, with a definite diagnosis made: SLDP if they had spontaneously completed puberty by age 18 years; HH if they had not commenced (complete, cHH), or had commenced but not completed puberty (partial, pHH), by this stage. Phenotypic data pertaining to auxology, Tanner staging, biochemistry, bone age and hormonal treatment at presentation and during puberty were retrospectively analysed.Results78 patients were included. 52 (66.7%) patients had SLDP and 26 (33.3%) patients had HH, comprising 17 (65.4%) pHH and 9 (34.6%) cHH patients. Probands were predominantly male (90.4%). Male SLDP patients presented with significantly lower height and weight standard deviation scores than HH patients (height p=0.004, weight p=0.021). 15.4% of SLDP compared to 38.5% of HH patients had classical associated features of HH (micropenis, cryptorchidism, anosmia, etc. p=0.023). 73.1% of patients with SLDP and 43.3% with HH had a family history of DP (p=0.007). Mean first recorded luteinizing hormone (LH) and inhibin B were lower in male patients with HH, particularly in cHH patients, but not discriminatory. There were no significant differences identified in blood concentrations of FSH, testosterone or AMH at presentation, or in bone age delay.DiscussionKey clinical markers of auxology, associated signs including micropenis, and serum inhibin B may help distinguish between SLDP and HH in patients presenting with pubertal delay, and can be incorporated into clinical assessment to improve diagnostic accuracy for adolescents. However, the distinction between HH, particularly partial HH, and SLDP remains problematic. Further research into an integrated framework or scoring system would be useful in aiding clinician decision-making and optimization of treatment.

We have studied dispersion of surface plasmon polaritons (SPPs) in the Kretschmann geometry (prism/Ag/dye-doped polymer) in weak, intermediate, and ultra-strong exciton–plasmon coupling regimes. The dispersion curves obtained in the reflection experiment were in good agreement with the simple model predictions at small concentrations of dye (Rhodamine 590, Rh590) in the polymer (Poly(methyl methacrylate), PMMA). At the same time, highly unusual multi-segment “staircase-like” dispersion curves were observed at extra-large dye concentrations, also in agreement with the simple theoretical model predicting large, small, and negative group velocities featured by different polariton branches. In a separate experiment, we measured angular dependent emission of Rh590 dye and obtained the dispersion curves consisting of two branches, one nearly resembling the SPP dispersion found in reflection and the second one almost horizontal. The results of our study pave the road to unparalleled fundamental science and future applications of weak and strong light—matter interactions.

During the main COVID-19 global pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18° North in Norway to 37.96° South in Australia, resulting in a data set of 25,174 rows, with each row being a unique interaction record for that date/site/plant species, and comprising almost 47,000 visits to flowers, as well as records of flowers that were not visited by pollinators, for over 1,000 species and varieties belonging to more than 460 genera and 96 plant families. The more than 650 species of flower visitors belong to 12 orders of invertebrates and four of vertebrates. In this first publication from the project, we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. The data generated from these global surveys will provide scientific evidence to help us understand the role that private gardens (in urban, rural and suburban areas) can play in conserving insect pollinators and identify management actions to enhance their potential.

BackgroundFibroblast growth factor 21 (FGF21) is an essential metabolic regulator that adapts to changes in nutritional status. Severe childhood undernutrition induces elevated FGF21 levels, contributing to growth hormone (GH) resistance and subsequent linear growth attenuation potentially through a direct action on chondrocytes.MethodsIn this study, we assessed expression of the components of both GH and FGF21 pathways in rare and unique human growth plates obtained from children. Moreover, we investigated the mechanistic interplay of FGF21 on GH receptor (GHR) signaling in a heterologous system.ResultsChronic FGF21 exposure increased GH-induced GHR turnover and SOCS2 expression, leading to the inhibition of STAT5 phosphorylation and IGF-1 expression. The clinical significance of FGF21 signaling through GH receptors was tested in nutritionally driven growth failure seen in very preterm (VPT) infants right after birth. VPT infants display an immediate linear growth failure after birth followed by growth catch-up. Consistent with the in vitro model data, we show that circulating FGF21 levels were elevated during deflection in linear growth compared to catch-up growth and were inversely correlated with the length velocity and circulating IGF1 levels.ConclusionsThis study further supports a central role of FGF21 in GH resistance and linear growth failure and suggests a direct action on the growth plate.

Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with current antifungal therapies. Current diagnostic methods have inadequate sensitivity and specificity and may have issues with accessibility or turnaround time. Patients with diabetes mellitus and immune compromise are predisposed to infection with these environmental fungi, but COVID-19 has established itself as a new risk factor. Mucorales also cause healthcare-associated outbreaks, and clusters associated with natural disasters have also been identified. Robust epidemiological surveillance into burden of disease, at-risk populations, and emerging pathogens is required. Emerging serological and molecular techniques may offer a faster route to diagnosis, while newly developed antifungal agents show promise in preliminary studies. Equitable access to these emerging diagnostic techniques and antifungal therapies will be key in identifying and treating mucormycosis, as delayed initiation of therapy is associated with higher mortality.

Introduction The COVID-19 pandemic has impacted medical students in many ways. They are not exempt from personal struggles caused by the health crisis, and many have faced similar challenges adapting to a new learning experience. The University of East Anglia (UEA) has initiatives in place to support medical students including the society Headucate UEA and the Wellbeing Champions scheme established by Norwich Medical School (NMS). Objectives Headucate aims to improve mental wellbeing by educational online webinars and social events aimed at university students. NMS Wellbeing Champions offer support and signpost students to resources and the wider student support system at the UEA. Methods Headucate was established in 2012 by NMS students that began running workshops at local secondary schools. Their work has expanded to include wellbeing workshops, social events for students and mental health first aid training, so members can provide peer support. Wellbeing Champions are medical student representatives responsible for completing mental health first aid training, communication between students and faculty, providing resources and signposting, creating mental health bulletin newsletters, and running socials exclusively for medical students. Results 100% of Headucate workshop attendees who completed anonymous feedback agreed that they enjoyed it and that it was useful. No feedback has been collected regarding the success of the Wellbeing Champions. This should be carried out to assess and enhance the project further. Conclusions More data is needed to establish the success of the initiatives at NMS and their impact on medical student’s wellbeing. Disclosure No significant relationships.

Headucate: University of East Anglia (UEA) is a student-led organisation aiming to raise awareness around Mental Health through their workshops and events. Events in the last year have included a 24-hour live stream TV fundraiser, UEA’s first Psychiatry and Mental Health conference, a mental health themed stand-up show, mental health assistance workshops, a suicide prevention evening and a variety of panels. Headucate has also collaborated with Beat, the UK’s leading eating disorder charity, to run training aimed at Norwich Medical School students, other healthcare students and Professionals. Headucate provides opportunities for their members, including research, education within the medical community, organising group projects, hosting poster competitions and by collaborating with likeminded initiatives. Workshops were designed to include common mental health conditions; wellbeing; advice regarding looking after yourself and others; ways to get for support and the impact of COVID-19 on our mental health. They are arranged and delivered by our members to school children and university students; they have been adapted to an online platform, which allowed us to reach a wider audience. Outcome measures demonstrating the impact of Headucate’s work were analysed via verbal, written and rated feedback, obtained from participants of workshops and events. Headucate workshops can help to improve mental health awareness and education in schools; however, it is only a local initiative. To educate schools outside of Norfolk, Headucate’s repeatable model can be used to create new branches of organisations that can spread nationwide; so mental health education in schools can be promoted across the UK.

Introduction Headucate: University of East Anglia, a university student-led society, was founded almost 10 years ago by medical students to promote mental health education and raise awareness and funds for mental health causes. Objectives Headucate aims to spread mental health awareness and reduce stigma by working with schools, universities, other societies and charities internationally. Methods Headucate delivers workshops for children aged 4-18 in primary and secondary schools, community and youth groups and university students. These sessions were delivered in-person pre-COVID and online as interactive webinars since 2020, to spark discussion around mental health, and provide information about the variety of supports available for young people. Results In the past decade, Headucate UEA has grown to become one of UEA’s largest student-led groups boasting over 175 members in 2020-2021 from all courses. Within the online world, Headucate’s events have reached worldwide. The initiative has received national recognition, won national student awards and has expanded to set up three further Headucate branches nationwide. Outreach has accelerated and the school workshops reached over 1,000 students in the past year. Conclusions Headucate has grown from strength to strength and has plans to continue to develop, with passionate student drivers behind the project. Expansion of the project could include a national mental health university directory, bringing together like-minded mental health advocate students around the country and creating new Headucate branches across the country. To further develop, Headucate could expand outreach to the elderly community as discussed by previous committee. Disclosure No significant relationships.

Introduction The dawn of COVID-19 brought new rules, restrictions, and lockdowns but this led to the unlikely fall of many sectors, including the charitable sector. There has been a significant decline in funding received by mental health charities, especially during the pandemic. This study looks at the subsequent impact on fundraisers and mental health promotion during COVID-19. Objectives The main aim was to uncover how the COVID-19 pandemic has affected the way that mental health charities fundraise, raise awareness, and promote mental health. This aimed to look at the impact of the COVID-19 pandemic on fundraisers supporting mental health charities and their opinion on whether fundraising has either helped or hindered mental health promotion. Methods Accounts from fundraisers and local representatives for mental health charities during the COVID-19 pandemic were analysed. Common themes looked at the impact, adaptation, and reasons why fundraisers decided to help during a tough period for the charitable sector. Results Mental health charities expressed difficulty in sourcing funds to support their users, especially in a vulnerable time. Fundraisers tried innovative ways to promote mental health and raise money for charities. Conclusions Altruism and understanding how precious services such as mental health charities are for the population was the main driver for fundraisers. Mental health charities adapted by turning to online communication and reached out to fundraisers to continually highlight the importance of mental health to their users and fundraisers. Disclosure No significant relationships.

Introduction TikTok is a free mobile application, that enables users to create short videos. TikTok has an estimated one billion monthly active users, comprised of a mostly younger audience. There has been a noticed rise in content discussing ADHD – hashtag ADHD on TikTok has 6.3 billion views. The discussions continue on Twitter, where users are reporting watching TikTok content explaining ADHD symptomatology, subsequently relating to the condition and requesting referrals to specialist psychiatry services. This study aims to identify key themes in discussions around TikTok and ADHD, and its ramifications. Objectives This study’s objective is to discuss the relationship between viewing ADHD content of TikTok and self-diagnoses of ADHD in young people. Methods In our study, Twitter posts were identified with the words ‘ADHD’ and ‘TikTok’ and established key themes relating to self-diagnosis of ADHD. Results Numerous tweets were found discussing individual’s experiences of self-diagnosis of ADHD after watching TikTok videos and relating with the symptomology. Furthermore, many users discussed their efforts to seek diagnosis from psychiatrists. These posts highlighted positive discussion of mental health, and the improvement in quality of life since diagnosis. Conclusions Many young people are self-diagnosing ADHD after viewing TikTok videos. This may improve mental health stigma, however the expertise of the video creators should be scrutinised. Furthermore, the impact on already stretched waiting lists should be considered, with individuals who’s perceived ADHD traits are not impacting on their quality of life. Disclosure No significant relationships.

Introduction Waiting times for gender identity services, even before the Covid-19 pandemic, have been a cause of concern. Despite the waiting time standard for planned elective care in the NHS being a maximum of 18 weeks, the average waiting time for a first appointment with a gender identity clinic is 18 months. This study aims to analyse the effect that these timings have on the transgender community, and whether they impact the risk of developing mental health conditions such as depression or anxiety. Objectives This study’s main aim is to analyse the correlation between waiting times and mental health burden in the transgender community. Methods A literature review and analysis on a transgender individual’s mental health and waiting times for Gender Identity Clinics; looking at any key themes and conclusions. Research papers were taken from MEDLINE, The International Journal of Transgender Health, Oxford Academic, SpringerLink and Emerald Insight, with studies publishing date ranging from 2014 – 2021. Results The transgender population were found to have higher rates of suicidal ideation, depression and self harm compared to the general population. Longer waiting times were found to contribute to feelings of low mood and suicidal ideation, as well as decreasing overall quality of life. Conclusions Longer waiting times can decrease a transgender individual’s quality of life and impact their overall mental wellbeing: especially with the impact of COVID-19 and the rise in referrals. Disclosure No significant relationships.

ABSTRACT Human cells identify invading pathogens and activate immune signaling pathways through a wide array of pattern recognition receptors, including DNA sensors. The interferon-inducible protein 16 (IFI16) is a nuclear DNA sensor that recognizes double-stranded DNA from a number of viral sources, including genomes of nuclear-replicating viruses. Among these is the prevalent human pathogen herpes simplex virus 1 (HSV-1). Upon binding to the HSV-1 DNA genome, IFI16 both induces antiviral cytokine expression and suppresses virus gene expression. Here, we used a multiomics approach of DNA sequencing techniques paired with targeted mass spectrometry to obtain an extensive view of the interaction between IFI16 and the HSV-1 genome and how this binding affects the viral DNA structure and protein expression. Through chromatin immunoaffinity purification coupled with next-generation DNA sequencing (ChIP-seq), we found that IFI16 binds to the HSV-1 genome in a sequence-independent manner while simultaneously exhibiting broad enrichment at two loci: UL30, the viral DNA polymerase gene, and US1 to US7. The assay for transposase-accessible chromatin with sequencing (ATAC-seq) revealed that these two regions are among the most accessible stretches of DNA on the genome, thereby facilitating IFI16 binding. Accessibility of the entire HSV-1 genome is elevated upon IFI16 knockout, indicating that expression of IFI16 globally induces chromatinization of viral DNA. Deletion of IFI16 also results in a global increase in the expression of HSV-1 proteins, as measured by parallel reaction monitoring-mass spectrometry of viral proteins representing 80% of the HSV-1 genome. Altogether, we demonstrate that IFI16 interacts with the HSV-1 genome in a sequence-independent manner, coordinating epigenetic silencing of the viral genome and decreasing protein expression and virus replication. IMPORTANCE Mammalian host defense against viral infection includes broad-acting cellular restriction factors, as well as effectors of intrinsic and innate immunity. IFI16 is a critical nuclear host defense factor and intrinsic immune protein involved in binding viral DNA genomes, thereby repressing the replication of nucleus-replicating viruses, including the human herpes simplex virus 1. What has remained unclear is where on the viral genome IFI16 binds and how binding affects both viral DNA structural accessibility and viral protein expression. Our study provides a global view of where and how a nuclear restriction factor of DNA viruses associates with viral genomes to exert antiviral functions during early stages of an acute virus infection. Our study can additionally serve as a systems-level model to evaluate nuclear DNA sensor interactions with viral genomes, as well as the antiviral outcomes of transcriptionally silencing pathogen-derived DNA.

Abstract Background The FLAIR trial in chronic lymphocytic leukaemia has a randomised, controlled, open-label, confirmatory, platform design. FLAIR was successfully amended to include an emerging promising experimental therapy to expedite its assessment, greatly reducing the time to reach the primary outcome compared to running a separate trial and without compromising the validity of the research or the ability to recruit to the trial and report the outcomes. The methodological and practical issues are presented, describing how they were addressed to ensure the amendment was a success. Methods FLAIR was designed as a two-arm trial requiring 754 patients. In stage 2, two new arms were added: a new experimental arm and a second control arm to protect the trial in case of a change in practice. In stage 3, the original experimental arm was closed as its planned recruitment target was reached. In total, 1516 participants will be randomised to the trial. Results The changes to the protocol and randomisation to add and stop arms were made seamlessly without pausing recruitment. The statistical considerations to ensure the results for the original and new hypotheses are unbiased were approved following peer review by oversight committees, Cancer Research UK, ethical and regulatory committees and pharmaceutical partners. These included the use of concurrent comparators in case of any stage effect, appropriate control of the type I error rate and consideration of analysis methods across trial stages. The operational aspects of successfully implementing the amendments are described, including gaining approvals and additional funding, data management requirements and implementation at centres. Conclusions FLAIR is an exemplar of how an emerging experimental therapy can be assessed within an existing trial structure without compromising the conduct, reporting or validity of the trial. This strategy offered considerable resource savings and allowed the new experimental therapy to be assessed within a confirmatory trial in the UK years earlier than would have otherwise been possible. Despite the clear efficiencies, treatment arms are rarely added to ongoing trials in practice. This paper demonstrates how this strategy is acceptable, feasible and beneficial to patients and the wider research community. Trial registration ISRCTN Registry ISRCTN01844152 . Registered on August 08, 2014