Developing a behaviour change intervention using information about greenhouse gas emissions to reduce liquid antibiotic prescribing.

Introduction: The determinants of antimicrobial prescribing often involve social influence, which can be harnessed through behaviour change techniques (BCTs). While previous studies have used BCTs to address antimicrobial resistance, there is a lack of evidence regarding their application to address climate change-related issues in antibiotic prescribing. This study aimed to develop a behaviour change intervention (BCI) using information about greenhouse gas emissions to reduce liquid antibiotic prescribing.

Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression.

The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP).

The burden of diabetes-associated multiple long-term conditions on years of life spent and lost.

Diabetes mellitus is a central driver of multiple long-term conditions (MLTCs), but population-based studies have not clearly characterized the burden across the life course. We estimated the age of onset, years of life spent and loss associated with diabetes-related MLTCs among 46 million English adults. We found that morbidity patterns extend beyond classic diabetes complications and accelerate the onset of severe MLTCs by 20 years earlier in life in women and 15 years earlier in men.

Role for DPP4 inhibitor therapy in cystic fibrosis related diabetes: A single centre experience.

Introduction: Insulin remains the only recommended medical treatment for cystic fibrosis related diabetes (CFRD) Whilst there is an established role for orally bioavailable incretin mimetic agents such as the dipeptidyl peptidase-4 inhibitors (DPP4-I) in Type 2 diabetes mellitus, there exists little data on their utility in CFRD.

Aim: To examine the use of DPP4-I therapy in patients with CFRD at a single large adult cystic fibrosis center.

Method: People with CFRD prescribed a DPP4-I were identified from our specialist CFRD clinic and records were retrospectively examined for indication for therapy, tolerability and effectiveness.

Decision making for health-related research outcomes that alter diagnosis: A model from paediatric brain tumours.

Aims: The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality.

Exploration of understanding of impactibility analysis and application through workshops to inform model design for population health management policy: a qualitative assessment.

Objectives: Assess understanding of impactibility modelling definitions, benefits, challenges and approaches.

Design: Qualitative assessment.

Setting: Two workshops were developed.

Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over trial.

Aim: To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec.

Materials And Methods: Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP).

Effects of home-based exergaming on cardio-metabolic and cognitive health in physically inactive individuals.

Aims: To examine the effects of a home-based exergame training over 6 weeks on cardio-metabolic and cognitive health, as well as training adherence, in physically inactive individuals.

Materials And Methods: Twenty participants were equipped with an exergame system specifically designed for use at home. Each participant performed at least three weekly exercise sessions at ≥80% of their individual maximum heart rate, over 6 weeks.

Early experience in use of videolaryngoscopy by a neonatal pre-hospital and retrieval service.

Objective: To describe initial experience with use of the Glidescope Go videolaryngoscope by an Australian neonatal pre-hospital and retrieval service.

Methods: We conducted a 31-month retrospective review of an airway registry for neonates intubated by MedSTAR Kids clinicians.

Results: Twenty-two patients were intubated using the Glidescope Go, compared with 50 using direct laryngoscopy.

DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification.

Aims: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology.

DNA methylation changes from primary cultures through senescence-bypass in Syrian hamster fetal cells initially exposed to benzo[a]pyrene.

Current chemical testing strategies are limited in their ability to detect non-genotoxic carcinogens (NGTxC). Epigenetic anomalies develop during carcinogenesis regardless of whether the molecular initiating event is associated with genotoxic (GTxC) or NGTxC events; therefore, epigenetic markers may be harnessed to develop new approach methodologies that improve the detection of both types of carcinogens. This study used Syrian hamster fetal cells to establish the chronology of carcinogen-induced DNA methylation changes from primary cells until senescence-bypass as an essential carcinogenic step.

Development of a Novel Home-Based Exergame With On-Body Feedback: Usability Study.

Background: With more than 1.4 billion adults worldwide classified as physically inactive, physical inactivity is a public health crisis leading to an increased risk of cardiometabolic diseases. Motivating and engaging training strategies are needed to tackle this public health crisis.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

Introduction: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.

Methods: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe.

Use and Perception of Telemedicine in People with Type 1 Diabetes During the COVID-19 Pandemic: A 1-Year Follow-Up.

In the spring of 2020, our research group circulated a worldwide survey with the aim of gathering information on the use and perception of telemedicine in people living with type 1 diabetes at the start of the COVID-19 pandemic. The data suggested that a large number of respondents had rapidly adopted to telemedicine, as in-person visits were not possible, and that this was perceived positively by many. In this study, we conducted a 1-year follow-up to investigate changes in opinions and experiences to telemedicine over the past year of the pandemic.

Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse.

Background: Less than 5% of medulloblastoma (MB) patients survive following failure of contemporary radiation-based therapies. Understanding the molecular drivers of medulloblastoma relapse (rMB) will be essential to improve outcomes. Initial genome-wide investigations have suggested significant genetic divergence of the relapsed disease.

Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study.

Background: Only few data are available on treatment-associated behavior of distinct rare CNS embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumors with multilayered rosettes (ETMR) are needed for development of differentiated treatment strategies.

Methods: Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n = 307).

Identifying cellular signalling molecules in developmental disorders of the brain: Evidence from focal cortical dysplasia and tuberous sclerosis.

Aims: We understand little of the pathogenesis of developmental cortical lesions, because we understand little of the diversity of the cell types that contribute to the diseases or how those cells interact. We tested the hypothesis that cellular diversity and cell-cell interactions play an important role in these disorders by investigating the signalling molecules in the commonest cortical malformations that lead to childhood epilepsy, focal cortical dysplasia (FCD) and tuberous sclerosis (TS).

Methods: Transcriptional profiling clustered cases into molecularly distinct groups.

A rare case of paediatric astroblastoma with concomitant MN1-GTSE1 and EWSR1-PATZ1 gene fusions altering management.

In a case of astroblastoma, methylation analysis was uninformative, with no clustering with known CNS-HGNET-MN1 cases. Whole genome sequencing however identified a novel MN1-GTSE1 gene fusion (image), confirming the diagnosis of astroblastoma, as well as an EWSR1-PATZ1 gene fusion. Whole genome sequencing, alongside methylation profiling and conventional neuropathology, will continue to lead to improved diagnostics and prognostication for children with brain tumours.

A case series of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC).

In this study, we report three paediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC).

Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity.

Immune-therapy is an attractive alternative therapeutic approach for targeting central nervous system (CNS) tumors and the constituency of the Tumor Immune Microenvironment (TIME) likely to predict patient response. Here, we describe the TIME of >6000 primarily pediatric CNS tumors using a deconvolution approach (methylCIBERSORT). We produce and validate a custom reference signature defining 11 non-cancer cell types to estimate relative proportions of infiltration in a panCNS tumor cohort spanning 80 subtypes.

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population.

Methylation-based algorithms for diagnosis: experience from neuro-oncology.

Brain tumours are the most common tumour-related cause of death in young people. Survivors are at risk of significant disability, at least in part related to the effects of treatment. Therefore, there is a need for a precise diagnosis that stratifies patients for the most suitable treatment, matched to the underlying biology of their tumour.

Application of physiologically based kinetic (PBK) modelling in the next generation risk assessment of dermally applied consumer products.

Next Generation Risk Assessment (NGRA) is a procedure that integrates new approach methodologies (NAMs) to assure safety of a product without generating data from animal testing. One of the major challenges in the application of NGRA to consumer products is how to extrapolate from the in vitro points of departure (PoDs) to the human exposure level associated with product use. To bridge the gap, physiologically based kinetic (PBK) modelling is routinely used to predict systemic exposure (C or AUC) from external exposures.