Zbtb16 mediates a switch between Fgf signalling regimes in the developing hindbrain.

Developing tissues are sequentially patterned by extracellular signals that are turned on and off at specific times. In the zebrafish hindbrain, fibroblast growth factor (Fgf) signalling has different roles at different developmental stages: in the early hindbrain, transient Fgf3 and Fgf8 signalling from rhombomere 4 is required for correct segmentation, whereas later, neuronal Fgf20 expression confines neurogenesis to specific spatial domains within each rhombomere. How the switch between these two signalling regimes is coordinated is not known. We present evidence that the Zbtb16 transcription factor is required for this transition to happen in an orderly fashion. Zbtb16 expression is high in the early anterior hindbrain, then gradually upregulated posteriorly and confined to neural progenitors. In mutants lacking functional Zbtb16, fgf3 expression fails to be downregulated and persists until a late stage, resulting in excess and more widespread Fgf signalling during neurogenesis. Accordingly, the spatial pattern of neurogenesis is disrupted in Zbtb16 mutants. Our results reveal how the distinct stage-specific roles of Fgf signalling are coordinated in the zebrafish hindbrain.

Segmentation and patterning of the vertebrate hindbrain.

During early development, the hindbrain is sub-divided into rhombomeres that underlie the organisation of neurons and adjacent craniofacial tissues. A gene regulatory network of signals and transcription factors establish and pattern segments with a distinct anteroposterior identity. Initially, the borders of segmental gene expression are imprecise, but then become sharply defined, and specialised boundary cells form. In this Review, we summarise key aspects of the conserved regulatory cascade that underlies the formation of hindbrain segments. We describe how the pattern is sharpened and stabilised through the dynamic regulation of cell identity, acting in parallel with cell segregation. Finally, we discuss evidence that boundary cells have roles in local patterning, and act as a site of neurogenesis within the hindbrain.

Opportunities of Flexible and Portable Electrochemical Devices for Energy Storage: Expanding the Spotlight onto Semi-solid/Solid Electrolytes.

The ever-increasing demand for flexible and portable electronics has stimulated research and development in building advanced electrochemical energy devices which are lightweight, ultrathin, small in size, bendable, foldable, knittable, wearable, and/or stretchable. In such flexible and portable devices, semi-solid/solid electrolytes besides anodes and cathodes are the necessary components determining the energy/power performances. By serving as the ion transport channels, such semi-solid/solid electrolytes may be beneficial to resolving the issues of leakage, electrode corrosion, and metal electrode dendrite growth. In this paper, the fundamentals of semi-solid/solid electrolytes (e.g., chemical composition, ionic conductivity, electrochemical window, mechanical strength, thermal stability, and other attractive features), the electrode-electrolyte interfacial properties, and their relationships with the performance of various energy devices (e.g., supercapacitors, secondary ion batteries, metal-sulfur batteries, and metal-air batteries) are comprehensively reviewed in terms of materials synthesis and/or characterization, functional mechanisms, and device assembling for performance validation. The most recent advancements in improving the performance of electrochemical energy devices are summarized with focuses on analyzing the existing technical challenges (e.g., solid electrolyte interphase formation, metal electrode dendrite growth, polysulfide shuttle issue, electrolyte instability in half-open battery structure) and the strategies for overcoming these challenges through modification of semi-solid/solid electrolyte materials. Several possible directions for future research and development are proposed for going beyond existing technological bottlenecks and achieving desirable flexible and portable electrochemical energy devices to fulfill their practical applications. It is expected that this review may provide the readers with a comprehensive cross-technology understanding of the semi-solid/solid electrolytes for facilitating their current and future researches on the flexible and portable electrochemical energy devices.

UK junior doctors' strikes and patients with cancer: a morally questionable association.

Doctors' strikes are legally permissible in the UK, with the situation differing in other countries. But are they morally permissible? Doug McConnell and Darren Mann have systematically attempted to dismiss the arguments for the moral impermissibility of doctors' strikes and creatively attempted to provide further moral justification for them. Unfortunately for striking doctors, they fail to achieve this. Meanwhile, junior doctors' strikes have continued in the UK through 2023 and have now extended into 2024. In this response, which focuses on the UK situation and specifically junior doctors' strikes in the National Health Service (NHS) in England, I will demonstrate a central problem with their arguments-namely that they underplay the harms caused by prolonged doctors' strikes by ignoring the harms to patients with cancer. This weakens their conclusion that strikes are morally permissible in terms of the conditions and thresholds they set. I then provide a psychological critique of their justification for strikes in terms of the interests of the public. It follows that invoking the controversial concept of supererogatory action is ungrounded but also absurd when you consider time-critical cancer care. If those representing striking doctors wish to maintain a modicum of moral respectability, they should mitigate for patients with cancer and negotiate reasonably and with urgency.

A systematic review of vestibular stimulation in post-stroke visual neglect.

Unilateral visual neglect is a condition that negatively impacts the lives of many stroke survivors. Studies have investigated different forms of vestibular stimulation as a potential therapy, but evidence is yet to be systematically reviewed. We therefore reviewed the effects of vestibular stimulation on outcomes of neglect and activities of daily living (ADL) for people with visual neglect. We searched relevant databases up until September 2022. Eligible articles included any form of vestibular stimulation, study design, or control condition. Included participants were 18 years or older, presenting with neglect following a haemorrhagic or ischaemic stroke. Relevant outcomes were clinically validated measures of neglect and ADL. Cochrane risk of bias tools were used to assess study quality. Meta-analyses and narrative methods were used to synthesize the data. Our search returned 17 relevant studies comprising 180 participants. Meta-analyses showed no difference between galvanic vestibular stimulation and sham conditions on outcomes, whereas caloric vestibular stimulation led to improvement compared to pre-stimulation scores. Narrative syntheses showed mixed results. Clinical and methodological heterogeneity was found both within and between studies. Overall, results were inconsistent regarding the effects of vestibular stimulation as a treatment for neglect. Further trials are warranted but require more careful methodological planning.

School-age outcomes among IVF-conceived children: A population-wide cohort study.

BACKGROUND: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. METHODS AND FINDINGS: Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in ≥2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program-Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Inverse probability weighting with regression adjustment was used to estimate population average causal effects. The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of -0.3% (95% CI -3.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI -0.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school. CONCLUSIONS: In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians.

A single cell transcriptome atlas of the developing zebrafish hindbrain.

Segmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at boundaries and segment centres, in part mediated by Fgf20 signalling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.

Insights into the Electrochemical Behavior of Manganese Oxides as Catalysts for the Oxygen Reduction and Evolution Reactions: Monometallic Core-Shell Mn/Mn3 O4.

Overcoming the sluggish electrode kinetics of both oxygen reduction and evolution reactions (ORR/OER) with non-precious metal electrocatalysts will accelerate the development of rechargeable metal-air batteries and regenerative fuel cells. The authors investigated the electrochemical behavior and ORR/OER catalytic activity of core-porous shell Mn/Mn3 O4 nanoparticles in comparison with other manganese dioxides (ß- and γ-MnO2 ), and benchmarked against Pt/C and Pt/C-IrO2 . Under reversible operation in O2 -saturated 5 M KOH at 22 °C, the early stage activity of core-shell Mn/Mn3 O4 shows two times higher ORR and OER current density compared to the other MnO2 structures at 0.32 and 1.62 V versus RHE, respectively. It is revealed that Mn(III) oxidation to Mn(IV) is the primary cause of Mn/Mn3 O4 activity loss during ORR/OER potential cycling. To address it, an electrochemical activation method using Co(II) is proposed. By incorporating Co(II) into MnOx , new active sites are introduced and the content of Mn(II) is increased, which can stabilize the Mn(III) sites through comproportionation with Mn(IV). The Co-incorporated Mn/Mn3 O4 has superior activity and durability. Furthermore, it also surpassed the activity of Pt/C-IrO2 with similar durability. This study demonstrates that cost-effective ORR/OER catalysis is possible.

Genetic characterization of dengue virus serotype 1 circulating in Reunion Island, 2019-2021, and the Seychelles, 2015-2016.

BACKGROUND: An unprecedent increase in the number of cases and deaths reported from dengue virus (DENV) infection has occurred in the southwestern Indian ocean in recent years. From 2017 to mid-2021 more than 70,000 confirmed dengue cases were reported in Reunion Island, and 1967 cases were recorded in the Seychelles from 2015 to 2016. Both these outbreaks displayed similar trends, with the initial circulation of DENV-2 which was replaced by DENV-1. Here, we aim to determine the origin of the DENV-1 epidemic strains and to explore their genetic characteristics along the uninterrupted circulation, particularly in Reunion. METHODS: Nucleic acids were extracted from blood samples collected from dengue positive patients; DENV-1 was identified by RT-qPCR. Positive samples were used to infect VERO cells. Genome sequences were obtained from either blood samples or infected-cell supernatants through a combination of both Illumina or MinION technologies. RESULTS: Phylogenetic analyses of partial or whole genome sequences revealed that all DENV-1 sequences from Reunion formed a monophyletic cluster that belonged to genotype I and were closely related to one isolate from Sri Lanka (OL752439.1, 2020). Sequences from the Seychelles belonged to the same major phylogenetic branch of genotype V, but fell into two paraphyletic clusters, with greatest similarity for one cluster to 2016-2017 isolate from Bangladesh, Singapore and China, and for the other cluster to ancestral isolates from Singapore, dating back to 2012. Compared to publicly available DENV-1 genotype I sequences, fifteen non-synonymous mutations were identified in the Reunion strains, including one in the capsid and the others in nonstructural proteins (NS) (three in NS1, two in NS2B, one in NS3, one in NS4B, and seven in NS5). CONCLUSION: In contrast to what was seen in previous outbreaks, recent DENV-1 outbreaks in Reunion and the Seychelles were caused by distinct genotypes, all likely originating from Asia where dengue is (hyper)endemic in many countries. Epidemic DENV-1 strains from Reunion harbored specific non-synonymous mutations whose biological significance needs to be further investigated.

Co-creating system-wide improvement for people with traumatic brain injury across one integrated care system in the United Kingdom to initiate a transformation journey through co-production.

BACKGROUND AND OBJECTIVE: There is a need for better integration of services across communities and sectors for people living with traumatic brain injury (TBI) to meet their complex needs. Building on insights gained from earlier pilot work, here we report the outcomes of a participatory workshop that sought to better understand the challenges, barriers and opportunities that currently exist within the care pathway for survivors of TBI. METHODS: A diverse range of stakeholders from the acute and rehabilitation care pathway and the health and social care system were invited to participate in a 3-h workshop. The participants worked in four mixed subgroups using practice development methodology, which promotes person-centred, inclusive and participatory action. RESULTS: Thematic analysis identified shared purposes and values that were used to produce a detailed implementation and impact framework for application at both the level of the care interface and the overarching integrated care system. A variety of enablers were identified that related to collective values and behaviours, case management, team leadership and integrated team working, workforce capability, evidence-based practice and resourcing. The clinical, economic, cultural and social outcomes associated with these enablers were also identified, and included patient safety, independence and well-being, reduced waiting times, re-admission rates, staff retention and professional development. CONCLUSION: The co-produced recommendations made within the implementation and impact framework described here provide a means by which the culture and delivery of health and social care services can be better tailored to meet the needs of people living with TBI. We believe that the recommendations will help shape the formation of new services as well as the development of existing ones. PATIENT OR PUBLIC CONTRIBUTION: Patient and public involvement have been established over a 10-year history of relationship building through a joint forum and events involving three charities representing people with TBI, carers, family members, clinicians, service users, researchers and commissioners, culminating in a politically supported event that identified concerns about the needs of people following TBI. These relationships formed the foundation for the interactive workshop, the focus of this publication.

Dizziness Directly Influences Postconcussion Symptoms and Is Predictive of Poorer Mental Health in UK Military Personnel: A Retrospective Analysis.

OBJECTIVE: To investigate the contribution of dizziness to postconcussion symptoms, depression, and anxiety symptoms. SETTING: Mild traumatic brain injury (mTBI) service, Defence Medical Rehabilitation Centre, Stanford Hall. PARTICIPANTS: Two hundred eighty-three UK military personnel from the Royal Navy, Royal Airforce, Royal Marines, and British Army. DESIGN: A retrospective analysis of data from the Ministry of Defence medical records database. MAIN MEASURES: Sixteen-item Rivermead Post Concussion Symptoms Questionnaire, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9, The Dizziness Handicap Inventory. RESULTS: Injuries from sports or falls were the most common mechanism of mTBI, accounting for 23%, respectively. Chi-square analysis indicated that individuals with dizziness and postconcussion symptoms (PCS) had greater severity of PCS, depression, and anxiety than those with PCS alone. Mediation analysis showed dizziness directly and independently influenced the severity of PCS, despite the indirect effects of mediating depression and anxiety symptoms. CONCLUSION: Comorbid dizziness and PCS were predictive of poorer mental health compared with PCS alone. In addition, dizziness directly influenced the severity of PCS irrespective of the indirect effects of mental health symptoms. These observations suggest that treating dizziness with vestibular rehabilitation may improve PCS and mental health.

Measuring the quality of skin cancer management in primary care: A scoping review.

Skin cancer is a growing global problem and a significant health and economic burden. Despite the practical necessity for skin cancer to be managed in primary care settings, little is known about how quality of care is or should be measured in this setting. This scoping review aimed to capture the breadth and range of contemporary evidence related to the measurement of quality in skin cancer management in primary care settings. Six databases were searched for relevant texts reporting on quality measurement in primary care skin cancer management. Data from 46 texts published since 2011 were extracted, and quality measures were catalogued according to the three domains of the Donabedian model of healthcare quality (structure, process and outcome). Quality measures within each domain were inductively analysed into 13 key emergent groups. These represented what were deemed to be the most relevant components of skin cancer management as related to structure, process or outcomes measurement. Four groups related to the structural elements of care provision (e.g. diagnostic tools and equipment), five related to the process of care delivery (e.g. diagnostic processes) and four related to the outcomes of care (e.g. poor treatment outcomes). A broad range of quality measures have been documented, based predominantly on articles using retrospective cohort designs; systematic reviews and randomised controlled trials were limited.

Spread of SARS-CoV-2 Variants on Réunion Island, France, 2021.

In January 2021, after detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, genomic surveillance was established on Réunion Island to track the introduction and spread of SARS-CoV-2 lineages and variants of concern. This system identified 22 SARS-CoV-2 lineages, 71% of which were attributed to the Beta variant.

The effect of probiotics on immunogenicity of spermatozoa in couples suffering from recurrent spontaneous abortion.

BACKGROUND: Impaired spermatozoa immunogenicity can result in pregnancy complications such as recurrent spontaneous abortion (RSA). Given that spermatozoa contact with microbiota, it is possible that inappropriate microbiota composition in the reproductive tract could result in the alteration of spermatozoa antigenicity. Probiotics, as a representative of microbiota, may therefore have a beneficial effect on this altered immunogenicity. The objective of this study was to determine the effect of probiotics on spermatozoa immunogenicity. METHODS: Twenty-five fertile couples and twenty-five RSA couples were included in this study. Spermatozoa were purified and treated with probiotics. Untreated and probiotic treated spermatozoa were evaluated for human leukocyte antigen (HLA) class I & II expression by flow cytometry. Untreated and probiotic treated spermatozoa were also cocultured with the wife's peripheral blood mononuclear cells (PBMC) for 12 days. Then, the supernatant was assessed for IgG and APCA by enzyme-linked immunosorbent assay (ELISA) and complement-dependent cytotoxicity (CDC) assay respectively. RESULTS: Probiotic treatment of spermatozoa leads to an increase of HLA class I & II expression in both the fertile and RSA groups. The probiotic treatment resulted in a decrease in both IgG and APCA in the fertile group, but an increase in both IgG and APCA in the RSA group. CONCLUSIONS: The results of this study suggest that a supplementary probiotic treatment may be useful in couples suffering from RSA with an immunologic cause, because it improves disturbed HLA expression on spermatozoa and improves disturbed APCA and IgG production in the presence of spermatozoa.

Whole-Genome Sequencing and Virulome Analysis of Escherichia coli Isolated from New Zealand Environments of Contrasting Observed Land Use.

Generic Escherichia coli is commonly used as an indicator of fecal contamination to assess water quality and human health risk. Where measured E. coli exceedances occur, the presence of other pathogenic microorganisms, such as Shiga toxin-producing E. coli (STEC), is assumed, but confirmatory data are lacking. Putative E. coli isolates (n = 709) were isolated from water, sediment, soil, periphyton, and feces samples (n = 189) from five sites representing native forest and agricultural environments. Ten E. coli isolates (1.41%) were stx2 positive, 19 (2.7%) were eae positive, and stx1-positive isolates were absent. At the sample level, stx2-positive E. coli (5 of 189, 2.6%) and eae-positive isolates (16 of 189, 8.5%) were rare. Using real-time PCR, these STEC-associated virulence factors were determined to be more prevalent in sample enrichments (stx1, 23.9%; stx2, 31.4%; eae, 53.7%) and positively correlated with generic E. coli isolate numbers (P < 0.05) determined using culture-based methods. Whole-genome sequencing (WGS) was undertaken on a subset of 238 isolates with assemblies representing seven E. coli phylogroups (A, B1, B2, C, D, E, and F), 22 Escherichia marmotae isolates, and 1 Escherichia ruysiae isolate. Virulence factors, including those from extraintestinal pathogenic E. coli, were extremely diverse in isolates from the different locations and were more common in phylogroup B2. Analysis of the virulome from WGS data permitted the identification of gene repertoires that may be involved in environmental fitness and broadly align with phylogroup. Although recovery of STEC isolates was low, our molecular data indicate that they are likely to be widely present in environmental samples containing diverse E. coli phylogroups. IMPORTANCE This study takes a systematic sampling approach to assess the public health risk of Escherichia coli recovered from freshwater sites within forest and farmland. The New Zealand landscape is dominated by livestock farming, and previous work has demonstrated that "recreational exposure to water" is a risk factor for human infection by Shiga toxin-producing Escherichia coli (STEC). Though STEC isolates were rarely isolated from water samples, STEC-associated virulence factors were identified more commonly from water sample culture enrichments and were associated with increased generic E. coli concentrations. Whole-genome sequencing data from both E. coli and newly described Escherichia spp. demonstrated the presence of virulence factors from E. coli pathotypes, including extraintestinal pathogenic E. coli. This has significance for understanding and interpreting the potential health risk from E. coli where water quality is poor and suggests a role of virulence factors in survival and persistence of E. coli and Escherichia spp.

Arctic marine forest distribution models showcase potentially severe habitat losses for cryophilic species under climate change.

The Arctic is among the fastest-warming areas of the globe. Understanding the impact of climate change on foundational Arctic marine species is needed to provide insight on ecological resilience at high latitudes. Marine forests, the underwater seascapes formed by seaweeds, are predicted to expand their ranges further north in the Arctic in a warmer climate. Here, we investigated whether northern habitat gains will compensate for losses at the southern range edge by modelling marine forest distributions according to three distribution categories: cryophilic (species restricted to the Arctic environment), cryotolerant (species with broad environmental preferences inclusive but not limited to the Arctic environment), and cryophobic (species restricted to temperate conditions) marine forests. Using stacked MaxEnt models, we predicted the current extent of suitable habitat for contemporary and future marine forests under Representative Concentration Pathway Scenarios of increasing emissions (2.6, 4.5, 6.0, and 8.5). Our analyses indicate that cryophilic marine forests are already ubiquitous in the north, and thus cannot expand their range under climate change, resulting in an overall loss of habitat due to severe southern range contractions. The extent of marine forests within the Arctic basin, however, is predicted to remain largely stable under climate change with notable exceptions in some areas, particularly in the Canadian Archipelago. Succession may occur where cryophilic and cryotolerant species are extirpated at their southern range edge, resulting in ecosystem shifts towards temperate regimes at mid to high latitudes, though many aspects of these shifts, such as total biomass and depth range, remain to be field validated. Our results provide the first global synthesis of predicted changes to pan-Arctic coastal marine forest ecosystems under climate change and suggest ecosystem transitions are unavoidable now for some areas.

Prevalence of Chronic Diseases, Depression, and Stress Among US Childcare Professionals During the COVID-19 Pandemic.

INTRODUCTION: Given their central role in supporting children's development, childcare professionals' overall physical and mental health is important. We evaluated the prevalence of chronic diseases, depression, and stress levels during the COVID-19 pandemic among US childcare professionals. METHODS: Data were obtained from US childcare professionals (N = 81,682) through an online survey from May 22, 2020, through June 8, 2020. We used multivariable logistic and linear regression models to assess the association of sociodemographic characteristics with 4 physical health conditions (asthma, heart disease, diabetes, and obesity), depression, and stress weighted to national representativeness. RESULTS: For physical health conditions, 14.3% (n = 11,717) reported moderate to severe asthma, 6.5% (n = 5,317) diabetes, 4.9% (n = 3,971) heart disease, and 19.8% (n = 16,207) obesity. For mental health, 45.7% (n = 37,376) screened positive for depression and 66.5% (n = 54,381) reported moderate to high stress levels. Race, ethnicity, and sex/gender disparities were found for physical health conditions but not mental health of childcare professionals during the COVID-19 pandemic. CONCLUSION: Our findings highlighted that childcare professionals' depression rates during the pandemic were higher than before the pandemic, and depression, stress, and asthma rates were higher than rates among US adults overall during the pandemic. Given the essential work childcare professionals provided during the pandemic, policy makers and public health officials should consider what can be done to support their physical and mental health.

Towards open, reliable, and transparent ecology and evolutionary biology.

Unreliable research programmes waste funds, time, and even the lives of the organisms we seek to help and understand. Reducing this waste and increasing the value of scientific evidence require changing the actions of both individual researchers and the institutions they depend on for employment and promotion. While ecologists and evolutionary biologists have somewhat improved research transparency over the past decade (e.g. more data sharing), major obstacles remain. In this commentary, we lift our gaze to the horizon to imagine how researchers and institutions can clear the path towards more credible and effective research programmes.

Congenital oesophageal stenosis in oesophageal atresia: underrecognised and often missed?

PURPOSE: Congenital oesophageal stenosis (COS) is characterised by an intrinsic oesophageal narrowing that is present, but not necessarily symptomatic at birth. Small studies report an association of COS with oesophageal atresia (OA) in up to 14% of OA cases. Although OA is usually appreciated shortly after birth, the diagnosis of a concomitant COS is frequently delayed. This risk may be increased with the current movement away from routine postoperative upper gastrointestinal (GI) contrast study following OA repair. We performed a systematic review of the literature to assess the timing of diagnosis of COS in patients with COS and OA and how this impacted on patient outcomes. METHODS: A systematic review in accordance with PRISMA guidelines was undertaken. Only patients with OA associated with COS were included. Delayed diagnosis was defined as presentation > 1 month of age. RESULTS: 14 full-text studies with a total of 131 patients were included. Diagnosis of COS was delayed in 62/131 (47%) patients. These children presented with symptoms of dysphagia and aspiration at a median age of 13.5 months (IQR 7-30 months). In total, 18/131 patients were identified at the initial operation, due to difficulty passing a tube distally into the stomach. The data on timing of contrast studies were provided in 60/131 (46%) patients. A routine postoperative contrast study was performed in 39/60 (65%) of these, of which COS was identified immediately in 28/39 (72%). A diagnosis of COS could also be made on retrospective review of the early contrast study in a further 6/39 patients, giving an overall sensitivity of 87%. CONCLUSION: The association of COS and OA may be underrecognised and diagnosis delayed if routine contrast study is not performed. Contrast studies, performed in the neonatal period are effective at detecting a concomitant COS (sensitivity > 87%). This review supports routine early contrast study after OA repair with specific consideration of the presence of COS.

Gastrostomies in children requiring long-term ventilation.

PURPOSE: Children requiring long-term ventilation (LTV) via tracheostomy often require enteral tube feeding. We sought to investigate what proportion of these children underwent gastrostomy insertion to inform decision making at time of tracheostomy formation. METHODS: A retrospective review of all children commenced on LTV via a tracheostomy at Royal Manchester Children's Hospital over a 9-year period (2012-2020). Data are presented as median [IQR]. RESULTS: Forty-one LTV patients had tracheostomy insertion with an average age of 167 days [101-604]. Reasons for tracheostomy insertion were upper airway obstruction (18), central neurological condition (7), neuromuscular condition (12) and lower respiratory tract disease (4). Twenty-two patients were born preterm and chronic lung disease of prematurity was a contributory factor in their requirement for LTV. Eight children had gastrostomies inserted prior to tracheostomy formation. A further 22 children had a gastrostomy inserted at an average of 139 days [99-227] following tracheostomy. Four children remained on nasogastric feed and the rest were fed orally. Seventy-three percentage of LTV children with tracheostomy were gastrostomy fed. Neither indication for LTV nor prematurity predicted whether a child was gastrostomy fed. CONCLUSION: The large majority of children requiring LTV are tube fed and gastrostomy insertion should be considered at time of formation of tracheostomy.