Graduates from life sciences, including nutrition, will be at the forefront of promoting environmental, social, and food systems sustainability. The requisite competencies for their future roles include systems thinking, interdisciplinary collaboration, and effective communication, which are essential to navigating the complex interrelationship between human health and the environment [1,2]. To address this need, a 'Living Laboratory’ (LL) within a higher education (HE) food service setting could enrich the traditional laboratory experience, allowing students to cultivate these skills through experiential learning. This project aimed to i) scope the published literature to characterise LL examples within a HE food environment and ii) explore the understanding and perceptions of a LL concept in a food service setting for final year student research projects among students and academics at King’s College London.

A systematic scoping review was conducted in accordance with PRISMA-ScR guidelines (Registration OSF:d7y96). Two databases were searched (PubMed/Medline, Web of Science) from January 2010 to July 2024 to identify articles reporting the design, implementation or evaluation of LL in HE food service settings. A narrative synthesis was performed, and the resulting themes were used to inform focus groups (KCL Ethics:LRM-23/24-42657) with academic staff (two groups, nine participants) and students (four groups, seven postgraduate and nine undergraduate participants). Focus group discussions were audio-recorded and transcribed verbatim. Data were analysed using an inductive thematic approach [3].

Twenty-one articles were included in the scoping review. Common terms used to describe the LL concept included ‘innovation’, ‘collaboration’, ‘diverse stakeholders’, ‘enabling students’ and ‘practical learning experiences’. Recommendations for implementing LLs were provided in six articles and included engagement and outreach with stakeholders; managing conflicts; assessing impact; and establishing ethical and governance frameworks. The focus group findings indicated that both students and academics view the LL concept as a dynamic, real-world setting, emphasizing engagement and collaboration with internal and external stakeholders. Academics perceived the educational benefits of LLs as fostering experiential learning and perceived the barriers to implementation as including a lack of resources, scheduling conflicts, insufficient stakeholder engagement and unclear governance frameworks. Students highlighted the importance of aligning projects with taught programme content. and identified challenges such as limited awareness, unequal engagement across disciplines, time constraints, and concerns about inclusivity and equity across campuses. Students agreed that the LL provided opportunities to develop skills and knowledge in sustainability, science communication and real-world evidence studies, opening new career options after graduation. Lastly, altruism to improve food environments for peers and future students was a significant driving factor in student engagement.

Implementing LLs in HE food service settings requires input from multiple stakeholders. This scoping project identified key considerations from both academic staff and students to inform the co-design of a LL in a HE food service setting.

Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero (F1) and in the second generation (F2). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation (F2) of Auckland Steroid Trial (AST) participants. In the AST, women (F0) expected to birth between 24 and 36 weeks’ gestation were randomised to betamethasone or placebo. When their children (F1) were 50 years old, they and their children (F2) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the F2 generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 F2 participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean (SD) 0.63 (1.45), N = 77 vs 0.41 (1.28), N = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.

New Zealand and Australian governments rely heavily on voluntary industry initiatives to improve population nutrition, such as voluntary front-of-pack nutrition labelling (Health Star Rating [HSR]), industry-led food advertising standards, and optional food reformulation programmes. Research in both countries has shown that food companies vary considerably in their policies and practices on nutrition(1). We aimed to determine if a tailored nutrition support programme for food companies improved their nutrition policies and practices compared with control companies who were not offered the programme. REFORM was a 24-month, two-country, cluster-randomised controlled trial. 132 major packaged food/drink manufacturers (n=96) and fast-food companies (n=36) were randomly assigned (2:1 ratio) to receive a 12-month tailored support programme or to the control group (no intervention). The intervention group was offered a programme designed and delivered by public health academics comprising regular meetings, tailored company reports, and recommendations and resources to improve product composition (e.g., reducing nutrients of concern through reformulation), nutrition labelling (e.g., adoption of HSR labels), marketing to children (reducing the exposure of children to unhealthy products and brands) and improved nutrition policy and corporate sustainability reporting. The primary outcome was the nutrient profile (measured using HSR) of company food and drink products at 24 months. Secondary outcomes were the nutrient content (energy, sodium, total sugar, and saturated fat) of company products, display of HSR labels on packaged products, company nutrition-related policies and commitments, and engagement with the intervention. Eighty-eight eligible intervention companies (9,235 products at baseline) were invited to participate, of whom 21 accepted and were enrolled in the REFORM programme (delivered between September 2021 and December 2022). Forty-four companies (3,551 products at baseline) were randomised to the control arm. At 24 months, the model-adjusted mean HSR of intervention company products was 2.58 compared to 2.68 for control companies, with no significant difference between groups (mean difference -0.10, 95% CI -0.40 to 0.21, p-value 0.53). A per protocol analysis of intervention companies who enrolled in the programme compared to control companies with no major protocol violation also found no significant difference (2.93 vs 2.64, mean difference 0.29, 95% CI -0.13 to 0.72, p-value 0.18). We found no significant differences between the intervention and control groups in any secondary outcome, except in total sugar (g/100g) where the sugar content of intervention company products was higher than that of control companies (12.32 vs 6.98, mean difference 5.34, 95% CI 1.73 to 8.96, p-value 0.004). The per-protocol analysis for sugar did not show a significant difference (10.47 vs 7.44, mean difference 3.03, 95% CI -0.48 to 6.53, p-value 0.09).In conclusion, a 12-month tailored nutrition support for food companies did not improve the nutrient profile of company products.

In mammals, pregnancy and lactation are marked by calcium stress and bone resorption, leading to reduced bone mineral density. In humans, these periods may partly explain the higher prevalence of osteoporosis in older women compared with men, but lactation patterns in modern humans may reflect cultural influences rather than natural conditions. The extent to which these findings apply to wild-living mammals remains unknown. We measured urinary C-terminal crosslinking telopeptide of Type I collagen (CTX-I) levels, a bone resorption marker, during pregnancy in wild and zoo-housed bonobos (Pan paniscus) and during lactation in wild bonobos. Studying wild-living primates such as bonobos can provide insights into ancestral reproductive adaptations. We found an increase in CTX-I levels towards the end of pregnancy in zoo-housed and primiparous wild females. Contrary to expectations, CTX-I levels during early lactation are lower than in other reproductive phases. This pattern diverges from the assumption that lactation increases bone resorption. Our findings suggest that wild bonobos may use physiological or behavioral strategies to modulate bone metabolism during lactation. These adaptations, shaped in natural environments, provide insight into evolutionary pressures on skeletal health and may inform strategies to mitigate bone loss in humans.

Background: Meningiomas are the most common intracranial tumors. Radiotherapy (RT) serves as an adjunct following surgical resection; however, response varies. RTOG-0539 is a prospective, phase 2, trial that stratified patients risk groups based on clinical and pathological criteria, providing key benchmarks for RT outcomes. This is the first study that aims to characterize the molecular landscape of an RT clinical trial in meningiomas. Methods: Tissue from 100 patients was analyzed using DNA methylation, RNA sequencing, and whole-exome sequencing. Copy number variations and mutational profiles were assessed to determine associations with meningioma aggressiveness. Tumors were molecularly classified and pathway analyses were conducted to identify biological processes associated with RT response. Results: High-risk meningiomas exhibited cell cycle dysregulation and hypermetabolic pathway upregulation. 1p loss and 1q gain were more frequent in aggressive meningiomas, and NF2 and non-NF2 mutations co-occurred in some high-risk tumors. Molecular findings led to the reclassification of several cases, highlighting the limitations of histopathologic grading alone. Conclusions: This is the first study to comprehensively characterize the molecular landscape of any RT trial in meningioma, integrating multi-omic data to refine treatment stratification. Findings align with ongoing genomically driven meningioma clinical trials and underscore the need for prospective tissue banking to enhance biomarker-driven treatment strategies.

Background: Recent research has demonstrated that DBS sites in Alzheimer’s (AD) and Parkinson’s (PD) influencing cognition are functionally connected to the subiculum. However, the results are mixed, and it is unclear how or if DBS site-subiculum connectivity can be optimized to improve patient cognition. Methods: We studied how subiculum connectivity influenced cognitive outcomes in both PD (subthalamic nucleus) and AD (fornix) DBS patients (total n = 110). We first confirmed DBS site-subiculum connectivity had opposite cognitive effects in each disease. We next investigated patient factors underlying these opposing effects. Lastly, we related our findings back to clinical practice to guide DBS programming in PD and AD. Results: DBS site-subiculum connectivity correlated with cognitive improvement in AD but decline in PD. This was dependent upon hippocampal atrophy; such that higher subiculum connectivity was beneficial when the hippocampus was atrophic but deleterious when it was intact. Finally, we related our findings back to anatomy with cadaveric dissections and present how DBS stimulation can be optimized to improve patient cognition. Conclusions: DBS site-subiculum connectivity influences cognition but depends on patient factors. Thus, to optimize cognition based on patient factors, DBS electrodes can be programmed to stimulate subregions with higher or lower subiculum connectivity.

Background: Ischemic stroke is a major cause of morbidity and mortality in Canada. Since 2015, mechanical thrombectomy has been the standard of care for eligible large vessel occlusions (LVOs), though anesthetic strategies remain variable. Methods: We conducted a single-center retrospective review of patients undergoing mechanical thrombectomy for anterior circulation LVOs between 2021 and 2023. Patients were categorized by anesthetic strategy (general anesthesia vs. conscious sedation), and outcomes, including time to recanalization, angiographic results (mTICI), and 90-day functional status (mRS), were compared. Statistical analyses included Student’s t-test, Mann-Whitney U-test, and Fisher’s exact test. Results: Among 226 patients, 177 (78%) received general anesthesia and 49 (22%) underwent conscious sedation. Baseline characteristics including sex, age, NIHSS, ASPECTS, collaterals, and laterality were similar between groups. Conscious sedation was associated with a statistically significant shorter time from arrival to the angiography suite to groin puncture (p=0.007), but no differences in time to recanalization (p=0.893), angiographic outcomes (p=0.987), or 90-day functional status (p=0.795) were observed. Conclusions: Conscious sedation led to faster procedural initiation, though no difference in clinical or radiographic outcome was observed. Anesthetic choice should be individualized based on patient and physician factors in acute mechanical thrombectomy.

Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Impaired glycaemic control is a major risk factor for developing type 2 diabetes (T2D), a worldwide health epidemic intrinsically linked to diet and obesity. Whey proteins (WP) are increasingly popular supplements that are a rich source of branched-chain amino acids (BCAA), essential for muscle protein synthesis and metabolic regulation. In humans, fasting plasma concentrations of BCAA are maintained around 350 µM but become chronically elevated by 10-25% in persons with T2D. Little is known about whether BCAA from WP impacts circulating BCAA concentrations and contributes to this phenomenon. This narrative review used a systematic search approach with relevant keywords to identify evidence from randomised controlled trials in normoglycaemic humans and those with insulin resistance or T2D, on the effects of WP intake on plasma BCAA and glycaemic control. This review is, to the authors’ knowledge, the first to specifically examine the effects of WP intake on plasma BCAA concentrations in relation to glycaemic control. Whilst the majority of acute studies identified (n=6) reported that WP consumption between 10 to 50 g significantly elevates postprandial BCAA and insulin responses (as evidenced by peak concentration and/or area under the curve), evidence from chronic studies (n=3) report inconsistent findings on the impact of 9 to 51g of WP per day on fasting BCAA and glycaemic control (e.g., fasting glucose and insulin, insulin clearance). Findings from this literature review highlight the need for further studies that investigate the relationship between WP consumption with BCAA and glycaemic control, and to determine underlying mechanisms of action.

Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

Background: Studies have found similar rates of functional independence for men and women after endovascular thrombectomy (EVT). Less is known regarding EVT-related procedural complications and symptomatic intracerebral hemorrhage (sICH) between sexes. Methods: Using the OPTIMISE registry including data from 20 comprehensive stroke centers across Canada between 1/1/2018 and 12/31/2022, we performed a retrospective descriptive analysis of patients divided between men and women. Hemorrhagic transformation on follow-up imaging with associated clinical deterioration was required to define sICH. Results: 3631 patients were included (1778 men and 1853 women) for analysis. Female patients were older (71.8±14.6 vs 68.0±13.1 years, p<0.001). There were no differences in sICH rates (2.5% men vs. 2% women, p= 0.388}. Procedural complication rates were not different between men and women (5.8 vs 5.6% p=0.76): dissection {26 (1.5%) vs. 30 (1.6%), p=0.804}, perforation {11 (0.6%) vs. 7 (0.4%), p=0.426}, embolization {25 (1.4%) vs. 25 (1.3%), p=0.996} and arterial access complications {45 (2.5%) vs. 43 (2.3%), p=0.761}. Conclusions: In this large multicentre registry of stroke patients undergoing EVT, men and women had similarly low and reassuring rates of sICH and procedural complications. This complements previous data showing similar functional outcomes for men and women after EVT.

Background: Inuit children have been observed to have high rates of macrocephaly, which leads to burdensome travel for medical evaluation, often with no pathology identified. Given reports that WHO growth charts may not reflect all populations, we compared head circumference (HC) measurements in a cohort of Inuit children with the WHO charts. Methods: We extracted HC data from a retrospective cohort study where, with Inuit partnership, we reviewed medical records of Inuit children, born between 2010-2013, and residing in Nunavut. We excluded children with preterm birth, documented neurologic/genetic disease, and most congenital anomalies. We compared HC values with the 2007 WHO charts. Results: We analyzed records of 1960 Inuit children (8866 data points). Most data were from ages 0-36 months. At all age points, the cohort had statistically significantly larger HC than WHO medians. At age 12 months, median HC were 1.3 cm and 1.5 cm larger for male and female Inuit children. Using WHO growth curves, macrocephaly was overdiagnosed and microcephaly underdiagnosed. Conclusions: Our results support the observation that Inuit children from Nunavut have larger HCs, and use of the WHO charts may lead to overdiagnosis of macrocephaly and underdiagnosis of microcephaly. Population specific growth curves for Inuit children should be considered.

Background: The combination of PARP inhibitor and immune checkpoint inhibitors have been proposed as a potentially synergistic combinatorial treatment in IDH mutant glioma, targeting dysregulated homologous recombination repair pathways. This study analyzed the cell-free DNA methylome of patients in a phase 2 trial using the PARP inhibitor Olaparib and the PD-1 inhibitor Durvalumab. Methods: Patients with recurrent high-grade IDH-mutant gliomas were enrolled in a phase II open-label study (NCT03991832). Serum was collected at baseline and monthly and cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) was performed. Binomial GLMnet models were developed and model performance was assessed using validation set data. Results: 29 patients were enrolled between 2020–2023. Patients received olaparib 300mg twice daily and durvalumab 1500mg IV every 4 weeks. The overall response rate was 10% via RANO criteria. 144 plasma samples were profiled with cfMeDIP-seq along with 30 healthy controls. The enriched circulating tumour DNA methylome during response periods exhibited a highly specific signature, accurately discriminating response versus failure (AUC 0.98 ± 0.03). Additionally, samples that were taken while on treatment were able to be discriminated from samples off therapy (AUC 0.74 ± 0.11). Conclusions: The cell-free plasma DNA methylome exhibits highly specific signatures that enable accurate prediction of response to therapy.