The Snails: A Simple Technique for Reduction of Frontal Bossing in Children With Scaphocephaly.

Objective: Scaphocephaly represents the most frequent single-suture craniosynostosis, with a male prevalence. In many cases, prominent frontal bossing (sphenocephaly) is the major aesthetic concern, typically in school-aged children. This aspect is also usually found in patients with late presentation (after 1 year of age).

Generating synthetic identifiers to support development and evaluation of data linkage methods.

Introduction: Careful development and evaluation of data linkage methods is limited by researcher access to personal identifiers. One solution is to generate synthetic identifiers, which do not pose equivalent privacy concerns, but can form a 'gold-standard' linkage algorithm training dataset. Such data could help inform choices about appropriate linkage strategies in different settings.

Golodirsen restores DMD transcript imbalance in Duchenne Muscular Dystrophy patient muscle cells.

Background: Antisense oligonucleotides (AON) represent a promising treatment for Duchenne muscular dystrophy (DMD) carrying out-of-frame deletions, but also show limitations. In a completed clinical trial golodirsen, approved by FDA to induce skipping of DMD gene exon 53 in eligible patients, we demonstrated increase in DMD expression and protein production, albeit with inter-patient variability.

Methods: Here, we investigate further the golodirsen mechanism of action using myotubes derived from MyoD transfected fibroblasts isolated from DMD patients at the baseline of the clinical trial SRP-4053.

Developing and testing a toolkit of interventions to improve adherence to non-invasive ventilation in children: the SPIRITUS study protocol.

Introduction: Non-invasive ventilation (NIV) is a known effective and safe treatment for children and young people with sleep disordered breathing (SDB). Adherence can be challenging and poor adherence risks undertreatment of SDB. While the risk factors for non-adherence have been widely reported, very few interventions have been tested in any capacity to address barriers to adherence.

Routine use of patient-reported experience and outcome measures for children and young people: a scoping review.

Background: Patient-reported outcome measures (PROMs) measure people's views of their health status whereas patient-reported experience measures (PREMs) are questionnaires measuring perceptions of their experience whilst receiving healthcare. PROMs/PREMs have the potential to enable children and young people (CYP) to be involved in decisions about their care and improve the quality of their care but it is not clear how often PROMs/PREMs are incorporated as part of standard care of CYP in the hospital setting. The aims of this scoping review were to understand the extent of the literature and map available evidence on the use, benefits, barriers and facilitators of PROMs/PREMs as part of standard care and treatment of CYP in hospitals.

An update on autoantibodies in the idiopathic inflammatory myopathies.

Myositis-specific autoantibodies (MSAs) have become pivotal biomarkers for idiopathic inflammatory myopathies and have revolutionized understanding of the heterogeneous disease spectrum that affects both adults and children. The discovery and characterization of MSAs have substantially enhanced patient stratification based on clinical phenotype, thereby facilitating more precise diagnosis and ultimately improving management strategies. Advances in immunoassay technologies in the past 20 years have further propelled the field forward, enabling the detection of a growing repertoire of autoantibodies with high specificity and sensitivity; however, evolving research over the past decade has revealed that even within antibody-defined subsets, considerable clinical diversity exists, suggesting a broader spectrum of disease manifestations than previously acknowledged.

Biomarkers of vaccine safety and efficacy in vulnerable populations: Lessons from the fourth international precision vaccines conference.

Vaccination has been a cornerstone of public health, substantially reducing the global burden of infectious diseases, notably evident during the COVID-19 pandemic caused by SARS-CoV-2. However, vulnerable populations (VPs), including those in extreme age groups and those with underlying health conditions, have borne a disproportionate burden of morbidity and mortality from infectious diseases. Understanding vaccine immunogenicity in these populations is crucial for developing effective vaccines.

Griscelli Syndrome Type 2: Comprehensive Analysis of 149 New and Previously Described Patients with RAB27A Deficiency.

Griscelli syndrome type 2 (GS2) is a rare, life-threatening immunodysregulatory disorder characterised by impaired cytotoxic activity leading to susceptibility to haemophagocytic lymphohistiocytosis (HLH) and hypopigmentation. We completed a literature review and analysis of clinical data of 149 patients with GS2 including 8 new patients.We identified three founder mutations which show diverse phenotypic profiles (RAB27A c.

Clinical Features, Biochemistry, Imaging, and Treatment Response in a Single-Center Cohort With Coenzyme Q Biosynthesis Disorders.

Background And Objectives: Disorders of coenzyme Q (CoQ) biosynthesis comprise a group of 11 clinically and genetically heterogeneous rare primary mitochondrial diseases. We sought to delineate clinical, biochemical, and neuroimaging features of these disorders, together with outcomes after oral CoQ supplementation and the utility of peripheral blood mononuclear cell (PBMNC) CoQ levels in monitoring therapy.

Methods: This was a retrospective cohort study, registered as an audit at a specialist pediatric hospital (Registration Number: 3318) of 14 patients with genetically confirmed CoQ biosynthesis deficiency, including 13 previously unreported cases.

What does a consent conversation for whole genome sequencing look like in the NHS Genomic Medicine Service? An observational study.

Patient choice consent for whole genome sequencing (WGS) through the Genomic Medicine Service in England covers consent to diagnostic testing and an invitation to the National Genomic Research Library (NGRL). Little is known about what consent conversations for WGS look like in practice. We audio-recorded and analysed the content and structure of consent appointments (n = 26) between healthcare professionals (HCPs) and parents of children with rare disease across seven NHS Trusts.

Parental Somatic Mosaicism Detected During Prenatal Diagnosis.

Objective: Accurate recurrence risks are essential for genomic counselling and parental reproductive choices. Historically, Sanger sequencing was used to test parental samples, which has a limited sensitivity of ∼ 10% for detecting somatic mosaicism. Next generation sequencing (NGS) methods, utilised for non-invasive prenatal diagnosis (NIPD) and trio prenatal exome sequencing in our laboratory, have greater sensitivity.

Implementation of a National Prenatal Exome Sequencing Service in England: Cost-Effectiveness Analysis.

Objective: Prenatal exome sequencing (pES) for diagnosing fetal structural anomalies commenced in the English National Health Service (NHS) in 2020. We evaluated cost-effectiveness to the healthcare system, and costs to families, of pES in addition to standard testing, compared to standard testing alone.

Design: A cost-effectiveness analysis combining costs, outcomes, parent and professional interview and professional survey data.

A spatial human thymus cell atlas mapped to a continuous tissue axis.

T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation and selection. In humans, this process starts in early fetal development and is highly active until thymic involution in adolescence. To map the microanatomical underpinnings of this process in pre- and early postnatal stages, we established a quantitative morphological framework for the thymus-the Cortico-Medullary Axis-and used it to perform a spatially resolved analysis.

Health impacts of takeaway management zones around schools in six different local authorities across England: a public health modelling study using PRIMEtime.

Background: In England, the number of takeaway food outlets ('takeaways') has been increasing for over two decades. Takeaway management zones around schools are an effective way to restrict the growth of new takeaways but their impacts on population health have not been estimated.

Methods: To model the impact of takeaway management zones on health, we used estimates of change in and exposure to takeaways (across home, work, and commuting buffers) based on a previous evaluation suggesting that 50% of new outlets were prevented from opening because of management zones.