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Jeffrey Wooliscroft,1 Rubeel Akram,1 Hafsa Zuberi,1 Betty Tong,1 Jane Gu,1 Aaron Hurd,1 Karanjit Kooner1,2 1Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Department of Ophthalmology, Veteran Affairs North Texas Health Care System Medical Center, Dallas, TX, USACorrespondence: Karanjit Kooner, Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA, Tel +1 (214) 648-4733, Fax +1 (214) 648-2270, Email Karanjit.Kooner@utsouthwestern.eduPurpose/Relevance: To determine the influence of hypertension (HTN), type 2 diabetes (DM2), migraine, and obstructive sleep apnea (OSA) on the onset of primary open-angle glaucoma (POAG) to enhance predictive accuracy.Methods: In this cross-sectional study, data for 389 eligible patients with POAG were collected through medical records review and phone surveys. All data were assessed collectively using stepwise multiple regression analysis to determine the relative contribution to age at POAG diagnosis. We used the following groups, based on age at diagnosis, HTN for patients with or without DM2 (model 1), HTN for patients with DM2 (model 2), DM2 for patients with or without HTN (model 3), and DM2 for patients with HTN (model 4).Results: In model 1, age at HTN diagnosis was associated with age at POAG diagnosis (β = 0.14; 95% CI, 0.01– 0.26, p = 0.04). In model 2, age at HTN diagnosis was not associated with age at POAG diagnosis (p > 0.05). In model 3, age at DM2 diagnosis was associated with age at POAG diagnosis (β = 0.37; 95% CI 0.16– 0.58, p = 0.001). In model 4, age at DM2 diagnosis was associated with age at POAG diagnosis (β = 0.40; 95% CI 0.00– 0.15, p = 0.003). Asian race/ethnicity was associated with early onset of POAG in model 3 (β = − 6.44; 95% CI − 12.34– 0.54, p = 0.033). OSA and migraine did not influence the onset of POAG.Conclusion: Our study found that the diagnosis of DM2 and HTN at an earlier age is associated with the early onset of POAG.Keywords: primary open-angle glaucoma, hypertension, type 2 diabetes, migraine, obstructive sleep apnea, onset of glaucoma

Underrepresented college students, particularly those attending a predominantly White institution (PWI), face unique challenges that undermine well-being and academic performance. However, support from natural mentors may mitigate the harms caused by these challenges and promote more positive college adjustment. The current study investigated how cumulative appraisal support, emotional support, informational support, and instrumental support from up to five natural mentors during students' first year of college were related to various concurrent and longitudinal outcomes. We found that 3 out of 4 types of social support were related to more positive, concurrent psychological or academic outcomes. Based on the results, we suggest that natural mentorship during students' first year of college has the potential to set a foundation for more positive adjustment among underrepresented students.

Functional analysis methods allow clinicians to determine the variable(s) that maintain destructive behavior. Previous reviews of functional analysis outcomes have included large samples of published and unpublished data sets (i.e., clinical samples). The purpose of this review was to conduct a large retrospective consecutive controlled case series of clinical functional analyses. We sought to identify the prevalence of differentiation, procedural modifications for undifferentiated and differentiated cases, and identified function(s) of destructive behavior. In addition, we extended the existing literature by determining whether functional analysis differentiation and function varied when single or multiple behavior topographies were consequated in the functional analysis. We discuss our findings considering previously published functional analysis reviews, provide avenues for future research, and offer suggestions for clinical practice.

The MYC oncogenic transcription factor is acetylated by the p300 and GCN5 histone acetyltransferases. The significance of MYC acetylation and the functions of specific acetylated lysine (AcK) residues have remained unclear. Here, we show that the major p300-acetylated K148(149) and K157(158) sites in human (or mouse) MYC and the main GCN5-acetylated K323 residue are reversibly acetylated in various malignant and nonmalignant cells. Oncogenic overexpression of MYC enhances its acetylation and alters the regulation of site-specific acetylation by proteasome and deacetylase inhibitors. Acetylation of MYC at different K residues differentially affects its stability in a cell type-dependent manner. Lysine-to-arginine substitutions indicate that although none of the AcK residues is required for MYC stimulation of adherent cell proliferation, individual AcK sites have gene-specific functions controlling select MYC-regulated processes in cell adhesion, contact inhibition, apoptosis, and/or metabolism and are required for the malignant cell transformation activity of MYC. Each AcK site is required for anchorage-independent growth of MYC-overexpressing cells in vitro, and both the AcK148(149) and AcK157(158) residues are also important for the tumorigenic activity of MYC transformed cells in vivo. The MYC AcK site-specific signaling pathways identified may offer new avenues for selective therapeutic targeting of MYC oncogenic activities.

Study aim: The purpose of this study was to examine if step-counts during PE and self-reported PA of elementary grade students varied based on the aerobic capacity.

Abstract Canada thistle is a pervasive perennial weed, causing challenges to agricultural and natural ecosystems globally. Although research has focused on the phenology, genetics, and control of Canada thistle, little is known about the rhizosphere microbiome and the role plant–microbe interactions play in invasion success. This study investigated the rhizosphere microbiome of Canada thistle across diverse climates, soils, and crops in the U.S. northern Great Plains. Soil and rhizosphere samples were collected and bacterial 16S and fungal ITS2 sequencing were performed to characterize the core microbiome and identify potential factors contributing to invasion success. Amplicon sequencing revealed a stable core microbiome that was detected in the Canada thistle rhizosphere across all locations. The core microbiome was dominated by the bacterial phyla Actinobacteriota and Proteobacteria and fungal phyla Ascomycota and Basidiomycota. Differential abundance analysis showed rhizosphere fungal communities were enriched in pathogen-containing genera with a 1.7-fold greater abundance of Fusaria and a 2.6-fold greater abundance of Gibberella compared to bulk soil. Predictive functional profiling showed rhizosphere communities were enriched (p

Abstract Background DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as “mosaic”. Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla. Results Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis. Conclusions Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.

Abstract Background Cannabidiol (CBD) is a widely available cannabis product with many claims as to potential health benefits including alleviating symptoms related to opioid use disorder (OUD). However, little is known as to how individuals with OUD perceive CBD, to what extent they may already be using CBD, and for what purposes. Methods A survey was conducted among individuals receiving treatment for OUD at the Addiction Institute of Mount Sinai in New York City from July 2021 to August 2023. The survey consisted of demographic questions, questions about opioid use, CBD use, and perceptions regarding CBD. Statistical analysis using ordinal logistic regression was employed to compare perceptions between CBD users and non-users while adjusting for age and race. Results Among 587 respondents, 550 completed the survey. Among all survey completers, 129 (23%) reported a history of using CBD for a variety of reasons including: anxiety (81, 62.8%), pain (65, 50.4%), sleep (63, 48.8%), depression (62, 48.1%), recreational purposes (32, 24.8%), or for other reasons (8, 6.2%). Of note, 22 (17.1%) respondents reported using CBD to control their addiction and 54 (41.9%) reported using CBD to ease opioid withdrawal symptoms. CBD users demonstrated more positive perceptions regarding its legality (β = 0.673, OR = 1.960, 95% CI [1.211, 3.176], p = .006), social acceptance (β = 0.718, OR = 2.051, 95% CI [1.257, 3.341], p = .004), and therapeutic potential compared to non-users. CBD users also had a more positive view of its potential future role in managing addiction (β = 0.613, OR = 1.846, 95% CI [1.181, 2.887], p = .007). Conclusions This study highlights a significant association between CBD usage and progressive views regarding CBD among individuals with OUD, suggesting a growing interest in CBD as a potential adjunctive therapy for individuals in substance use treatment. Some patients are already using CBD for anxiety, pain, sleep, depression, or as a harm reduction intervention to control their addiction or for opioid withdrawal symptoms. These findings underscore the importance of integrating patient perspectives into future research and treatment strategies involving CBD in the context of OUD.

Background Neonates undergoing emergency abdominal surgery frequently require a stoma; closing this stoma with a second operation is an essential part of recovery. Timing of closure varies. Optimal timing is unclear and would be best resolved through a randomised controlled trial; such a trial is likely to be challenging. Aim To determine if it is feasible to conduct a clinical trial comparing ‘early’ versus ‘late’ stoma closure in neonates. Design Mixed methods comprising three parallel workstreams incorporating: a clinician survey, prospective observational cohort study, parent interviews, focus groups, database analyses and consensus meeting. Setting Specialist neonatal surgical centres across the United Kingdom. Participants and data sources Neonatologists, neonatal surgeons, neonatal dietitians and neonatal nurses who care for neonates with stomas. Neonates with recent stoma, their parents and the clinicians looking after them. Three existing, overlapping clinical databases. Results One hundred and sixty-six professionals from all 27 neonatal surgical centres completed the survey: 6 weeks was the most common target time for stoma closure across clinical scenarios, although there was wide variation. Timing of closure was influenced by nutrition, growth and stoma complications. The prospective cohort study enrolled 56 infants from 8 centres. Infants were mostly preterm with necrotising enterocolitis or intestinal perforation. Clinicians identified extreme preterm gestation and clinical conditions as reasons for not randomising babies into a hypothetical trial comparing early and late stoma closure. Parents and healthcare professionals identified that comparator arms needed more clinical flexibility in relation to timing of stoma closure. Analysis of existing databases revealed wide variation in current timing of stoma closure in neonates and identified approximately 300 eligible infants for a trial per annum in the United Kingdom. Conclusions A trial of ‘early’ compared to ‘late’ stoma closure in neonates is feasible and is important to families and health professionals. The population of eligible babies in the United Kingdom is sufficient for such a trial. Challenges centre around lack of equipoise in certain scenarios, specifically: extremely preterm infants; infants waiting too long for stoma closure in the ‘late’ comparator; and logistical issues in closing a stoma at a trial-allocated time. These challenges are addressable by incorporating flexibility based on gestation at birth, communicating that both trial arms are standard practice and valid treatment options, and providing resources, for example, for operating lists. Future work We recommend the following population, intervention, comparator and outcome as a starting point to inform future trial design. Population: neonates with stomas (excluding those with a fixed treatment pathway). Intervention: stoma closure at 6 weeks and after 32 weeks post conceptual age. Comparator: expectant management with stoma closure undertaken when the clinical team determines is best for the infant. Primary outcomes: weight gain/growth or length of hospital stay. Study registration This study is registered as IRAS Project ID 278331, REC Reference 20/LO/1227. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128617) and is published in full in Health Technology Assessment; Vol. 28, No. 71. See the NIHR Funding and Awards website for further award information. Plain language summary Babies who develop a bowel problem soon after birth may need surgical treatment and a stoma (where the bowel is brought out into a bag on the tummy). Stomas can be life-saving but can also cause problems. They must be ‘closed’ with a second operation once the baby has got better. The timing of this second operation varies between hospitals and we do not know the best time to do it. To find out the best time to close a baby’s stoma, we wanted to conduct a clinical trial. This would mean some babies having their stoma closed ‘early’, and other babies ‘later’ and seeing which group did better. Babies would be put into the ‘early’ or ‘late’ group at random so that we could have a fair comparison. Because doing a trial may be challenging, we first set out to find out if a trial would be feasible in the Timing of Stoma Closure in Neonates study. What we did Found out what currently happens to babies with a stoma through a survey of healthcare staff and looking at data from several national databases. Collected data on 56 babies with stomas in 8 hospitals, including asking their doctors whether they would recruit these babies to a trial and when they would close their stoma. Interviewed parents of children who had had a stoma. Held focus groups with staff at the eight hospitals. Held a meeting for National Health Service staff and parents to discuss the way forwards. What we found Parents and doctors think this question is important and that a clinical trial is a good idea. Deciding on the timing of stoma closure in the trial and what we mean by ‘early’ and ‘late’ is critical to the success of a trial. The timing may need to take into account that some babies born extremely preterm may be difficult to include. A trial that compares how well infants grow and/or length of stay in hospital between babies having early or later stoma closure may well be feasible. What happens next The National Institute for Health and Care Research (research arm of the Department of Health and Social Care) will use this to information to help decide if they would like to fund a trial in the future. Scientific summary Background Neonates undergoing emergency abdominal surgery for problems such as necrotising enterocolitis (NEC), spontaneous intestinal perforation (SIP) or a congenital bowel obstruction frequently require a stoma. While stomas can be life-saving, they pose a number of challenges including fluid and electrolyte imbalance, local wound and skin problems, malnutrition and growth failure. Reversing (closing) these stomas with a second operation is therefore an essential part of an infant’s recovery. The timing of stoma closure is known to vary between hospitals and, indeed, clinicians and the best time remains unclear, with conflicting evidence from published studies of low methodological quality. Rationale Determining the best time to close stomas in neonates is imperative, as it has significant implications for: infant health outcomes (e.g. stoma complications and growth) families (e.g. reduced neonatal unit stay, healthcare burden, time off work) healthcare providers [e.g. neonatal unit bed-days, parenteral nutrition (PN) use, surgery, cost]. In addition, reducing unwarranted variability in surgical care is a key priority for the NHS. The most methodologically robust way to determine optimal timing of stoma closure would be through an adequately powered randomised controlled trial (RCT). A trial of different stoma closure times in neonates is likely to be challenging, due to: the patient group who have heterogenous underlying diseases and comorbidities clinician factors such as willingness to recruit parent factors such as trial acceptability. This study aimed to explore these potential challenges and determine if a trial comparing ‘early’ and ‘late’ stoma closure is feasible. Aims The overarching aim of the Timing of Stoma Closure in Neonates (ToSCiN) study was to answer the question: is it feasible to conduct a RCT comparing ‘early’ versus ‘late’ stoma closure in neonates? Objectives The specific objectives of the ToSCiN study were: to establish current UK practice for stoma closure in neonates to determine whether there is equipoise among clinicians (neonatal surgeons and neonatologists) and allied health professionals (specialist nurses and dietitians) over when it is best to close stomas in neonates to define ‘early’ and ‘late’ stoma closure for a potential trial to define a population of neonates for inclusion in a trial (in whom there is significant uncertainty over timing) and determine how many infants are eligible for inclusion to establish the most appropriate design and outcome measures for a trial to determine the willingness of parents, neonatal surgeons and neonatologists to include neonates in a trial that would randomise to ‘early’ or ‘late’ stoma closure and identify potential barriers to recruitment to assess the suitability of using routinely collected data for gathering clinical information for a trial. Methods The ToSCiN study used a mixed-methods approach (qualitative and quantitative methodology) and comprised three parallel workstreams. Workstream 1: Survey of clinician and allied health professional perspectives on neonatal stoma closure An online survey was sent to clinicians and allied health professionals involved in the care of newborn infants with stomas at neonatal surgical units across the UK. The survey questions and a series of clinical scenarios to explore current practice/preferences, perspectives on ‘early’ versus ‘late’ stoma closure, which groups of infants should be included in a trial comparing these, preferred trial design including outcomes and barriers to achieving the optimal timing of closure. Workstream 2: Parent and clinician perspectives regarding a clinical trial of neonatal stoma closure This workstream took place in eight UK neonatal surgical centres and comprised three elements: (2.1) An observational cohort study of neonates who had a stoma formed Key clinical and demographic information was recorded prospectively. The data set comprised factors that could influence the timing of stoma closure and outcomes which are likely to be important in a future trial. (2.2) Questionnaires for the principal clinicians (surgeon and neonatologist) caring for each infant recruited to the cohort study These were completed at three time points and explored the acceptability of a hypothetical trial to clinicians for each infant. Time points: (1) approximately 1 week after stoma formation to explore randomising the infant to a trial, (2) 6 weeks after stoma formation to explore following an allocation to early closure intervention and (3) 12 weeks after stoma formation to explore following an allocation to late closure comparator. (2.3) A qualitative study incorporating: (1) focus groups with clinicians and (2) interviews with parents of neonates who had a stoma Multidisciplinary healthcare professional focus groups explored equipoise, current practice and views on early versus late closure, willingness to recruit to a trial, acceptability of a trial and prioritised outcome measures. Parents of infants in the cohort study and additional parents recruited via social media were invited for a telephone or video interview. Their views were explored on: having a child with a stoma, acceptability of a trial, timing of recruitment, potential barriers to trial participation, trial participant information materials, approach to consent for a trial and prioritised outcome measures. Workstream 3: Analysis of three existing national databases Analyses were carried out on three existing national data sets [from the National Neonatal Research Database (NNRD), The British Association of Paediatric Surgeons Congenital Anomalies Surveillance System (BAPS-CASS) and Hospital Episode Statistics – Admitted Patient Care (HES-APC)]. The analyses aimed to: (1) establish current UK practice, (2) define a population for trial inclusion and provide the number of eligible infants and (3) establish values for key outcome measures. Consensus meeting This was held using an online video platform at the end of the study period when data collection and preliminary analysis had been completed. Professionals and parents previously involved were invited and further parents were recruited via social media. A summary of results from the three workstreams was presented to attendees. Facilitated small group discussions took place, followed by a summary of small group discussions presented by group facilitators to all attendees, and electronic voting was conducted about trial acceptability and design. Results Workstream 1 Results One hundred and sixty-six professionals completed the survey with at least one respondent from each of the 27 UK centres. Six weeks was the most commonly stated target time for closure across all scenarios, although there was a high degree of variability, with intervals of 12 weeks or more frequently advocated. While 70–76% of respondents preferred closure prior to discharge in preterm infants and a term infant with jejunostomy, only 46% preferred this in term infants with ileostomy. A sizeable proportion (41%) use weight, rather than time, to determine when to close a stoma. Thematic analysis of free text identified nine key themes influencing decision-making, mostly related to nutrition, growth and stoma complications. With regard to potential trial design, 86% of respondents indicated they would include preterm infants with NEC/SIP and 72% term infants with other conditions. Closure at 6 weeks was the most commonly cited timing of early intervention; the preferred later time point was 12 weeks. Growth was most commonly selected as the favoured primary outcome for a trial, followed by time to full feeds, length of stay and duration of PN. Workstream 2 Results Cohort study Fifty-six infants were enrolled from eight UK units. Infants were mostly preterm (44/56), with median birthweight 961 g (range 415–3962 g). The cohort comprised 37 infants with NEC/SIP and 19 with other diagnoses. Most stomas were in the small bowel, formed at a median of 8 days (range 1–80 days). At 1 week following stoma formation, 18/56 infants were mechanically ventilated, 8 were receiving inotropes and 13 had received blood products in the preceding 24 hours. At this point, surgeons stated they would be willing to randomise 31 infants (59%) into a hypothetical trial of 6- versus 12-week closure. The commonest reason for not being willing was the infant being ‘too small or premature’. At 6 weeks post stoma, median weight was 2024 g (range 795–4460 g) and nine remained ventilated. Eighty per cent (42/56) were reported to have gained weight in the past week. Median enteral feed volume was 127 ml/kg/day, stoma output was < 20 ml/kg/day in 86% and stoma-related complications were reported in one-third. Surgeons would be willing to follow theoretical trial allocation for ‘early’ closure in 17/56 (33%). In nine infants, the stoma had already been closed. The main reasons for not being willing to follow trial allocation were current clinical status and size. Among infants whom surgeons said they would not be willing to follow trial allocation, most (16/25) were < 28 weeks’ gestation at birth and were lighter (median weight 1609 vs. 2090 g). Twelve weeks after stoma formation, median weight was 2548 g and 10% (4/52) remained ventilated. Most (23/42; 55%) were still receiving PN (a higher proportion than at 6 weeks) and 12% (5/42) were not receiving any enteral feed. Stoma-related problems were present in one-third and one-quarter had stoma output > 20 ml/kg/day. Surgeons stated they would be unwilling to follow trial allocation of closure at 12 weeks in 24 infants: 12 of these had required earlier stoma closure and 9 (mainly premature infants) were considered unsuitable for stoma closure for a variety of mainly clinical reasons (rather than logistical or family factors). Again, most infants for whom the surgeon was unwilling to follow trial allocation were < 28 weeks' gestation at birth (13/24). Overall stoma closure took place before the end of the data collection period in 82% (46/56 infants, 4 infants died with a stoma in situ and 6 infants still had a stoma). Median time to closure was 9.9 weeks (range 4.4–28.3 weeks), at median 88 days of age and weight of 2631 g. Qualitative study We interviewed 24 parents (17 mothers, 7 fathers) of babies who required a stoma in the last 3 years in the UK (July 2021–February 2022). Fifteen parents were recruited via hospital sites and nine via social media. Thirty-six staff (14 surgeons, 10 consultant neonatologists, 6 neonatal surgical nurses, 2 research nurses, 1 dietitian and 3 ‘other’ roles) from five study sites took part in one of six focus groups (November–December 2021). Most parents and staff considered the proposed ToSCiN trial to be acceptable and wanted the research question to be answered. Staff would be willing to randomise babies, except the most extremely preterm, to the trial and parents would hypothetically consent to their baby taking part if the ‘emotive’ ‘early’ (6 weeks) and ‘late’ (12 weeks) terminology was changed. Some parents and staff, however, had clear trial arm preference and concerns about the alternative trial arm. They felt that decisions about when to close a stoma should be led by the overall health and well-being of the baby. Stoma-related factors, logistical and organisational factors and family factors also influenced views on acceptable timing of stoma closure. These findings highlight potential challenges for recruitment and retention and trial success. Workstream 3 Results While direct comparison was limited by differences in data set populations and coverage, there was a reasonably consistent number of potentially eligible infants with a stoma for NEC/SIP across data sets, with 163 in 1 year in the BAPS-CASS cohort and mean annual volumes of 193 (NNRD) and 192 (HES-APC). HES-APC was used to estimate non-NEC infant numbers, as it had the most comprehensive coverage, with a mean of 118 per year. The total UK population of potentially eligible infants would therefore be approximately 300 per annum. Median stoma durations for babies with NEC/SIP were as follows: BAPS-CASS 63 days; NNRD 60 days and HES-APC 78 days. For infants with stomas for other reasons, closure was usually earlier: NNRD 45 days; HES-APC 74 days; and in the BAPS-CASS meconium ileus cohort, 51 days. HES-APC included babies who were discharged home with a stoma in situ, hence longer median stoma durations. Consensus meeting The consensus meeting was attended by 52 individuals from a range of health professional and non-professional backgrounds, including 7 parents. Voting on key aspects of trial design showed: (1) 83% favoured including all infants with a stoma, (2) 58% favoured comparing closure at 6 weeks after stoma formation with expectant management rather than comparison to a specific late timepoint, and (3) the favoured primary outcomes were weight gain/growth (38%) and length of hospital stay (32%). Conclusions We found that a randomised trial of early compared to late stoma closure in neonates is feasible and is important to families and health professionals. We identified the following components as being critical to a successful future trial: comparison of closure at 6 weeks versus expectant management comparison that accounts for completed gestational age, rather than solely duration of stoma. We identified the potential population and outcomes for such a trial and established that a sufficient population exists in the UK. We also identified that a trial comparing ‘early’ and ‘late’ closure at rigidly defined time points (e.g. closure at 6 compared to 12 weeks) would not be feasible. The principal challenge for trial conduct was found to be the ‘baby-led’ narrative that came through strongly from study participants. Parents and professionals appeared to lack equipoise in certain scenarios. However, this lack of personal equipoise is not exclusive to ToSCiN, and similar themes have been overcome in trials in the past (including complex surgical trials) by optimising communication. Our findings provide valuable insight into how best to do this in a future trial. Other challenges identified include: (1) concerns about inclusion of extremely preterm infants, (2) concerns about infants waiting too long for stoma closure if randomised to the ‘late’ comparator arm and (3) logistical arrangements for closing a stoma at the time dictated by trial allocation. These challenges are eminently addressable, by designing the trial to: (1) incorporate a degree of flexibility (e.g. using ‘expectant management’ as the comparator), (2) make allowances for certain groups (e.g. having a higher corrected gestational age limit for extremely preterm infants) and (3) ensure parents and professionals are aware both trial arms are standard practice and valid treatment options. Key research recommendations We recommend the following population, intervention, comparator and outcome (PICO) as a starting point to inform the design of a future trial: Population: neonates with stomas, excluding those with a stoma as part of a fixed treatment pathway, for example, anorectal malformations and Hirschsprung’s disease. Intervention: stoma closure at 6 weeks post stoma formation and where 32 weeks post-conceptual age has been reached. Comparator: expectant management with stoma closure undertaken when the clinical team determines is best for the infant. Outcomes: weight gain/growth or length of hospital stay should be the primary outcome measure. In order to optimise a trial, we recommend the following practical steps: Involve higher volume neonatal surgical centres for efficient recruitment. Ensure trial staff at each centre are highly trained regarding current standard practice and equipoise. Approach parents 1–2 weeks after stoma formation. Provide resources to centres to permit stoma closure as per the trial protocol, for example, for ring-fenced operating theatre time and possibility of extended hospital stay. Study registration This study is registered as IRAS Project ID 278331, REC Reference 20/LO/1227. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128617) and is published in full in Health Technology Assessment; Vol. 28, No. 71. See the NIHR Funding and Awards website for further award information.

Noncompliance is a common caregiver concern that can have adverse effects on the learner. Although functional analysis is often employed for other forms of problem behavior (e.g., aggression, property destruction), it is infrequently conducted for noncompliance. Noncompliance is often hypothesized to be maintained by escape from demands. However, to date, no study has examined the prevalence of variables that maintain noncompliance or intervention outcomes despite their importance in informing intervention. Thus, the purpose of this review was to conduct a systematic literature review of published functional analysis of noncompliance to determine the prevalence of environmental variables that maintain noncompliance and subsequently examine the efficacy of noncompliance interventions based on functional analysis outcomes. Results indicate noncompliance was maintained by escape from demands in half of the studies identified, and consequence-based interventions were more efficacious than antecedent-based interventions.

Abstract The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p

ABSTRACTKelp aquaculture is typically a two-stage process, with an indoor nursery phase and a grow-out phase at sea. For the successful development and implementation of commercial kelp aquaculture, production of viable seeded lines in the nursery is essential. This study investigated optimal nursery conditions of three kelp species native to Tasmania, Australia: Ecklonia radiata, Lessonia corrugata, and Macrocystis pyrifera. The interactive effects of temperature (12°C, 15°C, and 18°C) and light level (~30 µmol photons s−1 m−2, and ~ 60 µmol photons s−1 m−2) on sporophyte length, sporophyte density, and contamination of spools were examined over a 34-day period. The optimal temperature and light levels were 15°C and 30 µmol photons m−2 s−1 for E. radiata, 12°C and 60 µmol photons m−2 s−1 for L. corrugata, and 12°C and 30 or 60 µmol photons m−2 s−1 for M. pyrifera. Under these optimal conditions, the mean ± SEM sporophyte lengths after 34 days were 0.60 ± 0.02 mm, 1.04 ± 0.04 mm, and 0.60 ± 0.01 mm for E. radiata, L. corrugata, and M. pyrifera, respectively. The mean ± SEM sporophyte densities for each of these three species were 15.5 ± 6.2 sporophytes cm−1 of line, 10.8 ± 5.9 sporophytes cm−1 of line, and 19.3 ± 8.1 sporophytes cm−1 of line, respectively. Contamination increased with increasing temperature and was not significantly affected by light level. This work highlights the need for a species- and ecotype-specific approach in the nursery phase to ensure successful seaweed aquaculture outcomes in new regions of cultivation.

The experience of inner light and ecstasy is widely accepted as a universal mystical experience, regardless of cultural or religious context. While one can read first-hand accounts in the historical record, the direct experience of light remains elusive for most people. This study analyzes a series of dream-based experiences of light provided by a single subject. In our analysis of 19 dreams, we pursue a process-oriented, relational analysis based on co-creative dream theory, which views the dream as an interactive experience in real time rather than a fixed product of the unconscious mind. By analyzing dreams as relational events, in which the metaphoric content emerges alongside the dreamer’s responses, we see how the dream ego influences the outcome through feelings, choices, and reactions. Through this analysis, we identify an array of subjective antecedents to the experience of light and provide a potential avenue of access to the core mystical experience.

Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors.