Anthocyanins, a flavonoid subclass present in certain blue, purple and red fruits and vegetables, have potential neuroprotective properties due to their anti-inflammatory, antioxidant, and signalling effects(1). Clinical and epidemiological studies of anthocyanins provide promising evidence for attenuation of memory loss and improved cognitive function(2). We investigated the effects of anthocyanins, provided through diet or supplementation, on cognitive function and related parameters(3). A multi-centre, 24-week randomised, parallel 3-arm clinical trial was conducted in participants aged 60–85y with self-reported memory complaints and scoring ≤ 13 on the Memory Index Score within the Telephone Montreal Cognitive Assessment (T-MoCA). Participants were randomised to high anthocyanin diet, freeze-dried product derived from blackcurrants (250 mg anthocyanins/day), or control (placebo). The primary outcome was auditory episodic memory functioning. Secondary outcomes were additional cognitive functions, subjective memory complaints and self-reported depression symptoms, blood pressure, inflammatory biomarkers, lipid profile, vascular and microvascular endothelial function tests, and gut microbiota. Mixed linear modelling evaluated changes over time. Gut microbial abundance (alpha diversity) was measured using Shannon Simpson’s Index and association between anthocyanin intake and taxa level was assessed using the MaAsLin2 multivariable regression model. Of 110 participants enrolled (mean age 69.2 y SD 6.7; 36 males, 74 females), 94 completed the study. Median anthocyanin intake increased by 76.7 mg, 252.1 mg, and 2.9 mg in the diet, active powder, and control groups, respectively. There was no treatment*time effect on any primary or secondary outcomes. A time effect was observed for the majority of psychometric tests. At baseline, participants with habitual anthocyanin intake ≥ 10 mg/day performed better on a number of cognitive tests compared to those with higher intakes (p < 0.05). They also had a clear difference in microbial abundance with Bacteroides sp. enriched in the higher anthocyanin group, compared to Enterococcus sp. enriched in the lower anthocyanin group. The active powder group had an increase in alpha diversity (p = 0.074) at follow-up which was more pronounced in in participants with a low habitual anthocyanin intake at baseline. In conclusion, this clinical trial found no significant effect of dietary or supplemental anthocyanins, on any of the investigated outcomes in older adults with self-reported memory complaints, except potential improvements in the gut microbiome in the active powder group. We postulate that the potential anti-inflammatory, antioxidant, and signalling effects of anthocyanins were insufficient to significantly modulate any outcomes due to participants’ overall good health and lack of relevant cognitive decline. We recommend future interventional studies focus on subjects with low habitual anthocyanin intakes, those with diagnosed cognitive impairment, such as Mild Cognitive Impairment and dementia, and those with more severe comorbidities, particularly chronic inflammatory conditions.

The two-way interaction between the unsteady flame heat release rate (HRR) and acoustic waves can lead to combustion instability within combustors. Previous studies have typically characterised premixed flame responses to pure harmonic forcing, assuming dynamically linear or weakly nonlinear behaviour, to quantify flame–acoustic interactions. By combining third-order asymptotic analysis with numerical simulations of the $G$-equation, this study investigates the nonlinear response of laminar premixed V-flames subjected to dual-frequency velocity perturbations ($St_1$ and $St_2$, dimensionless frequencies). The positive correlation between disturbance propagation speed $u_c$ and frequency $St$ is captured by integrating a velocity-potential model with calibration against existing experimental data. The mechanism by which the disturbance at one forcing frequency, say $St_2$, affects the flame dynamic response at the other forcing frequency, $St_1$, is studied in detail. The perturbation at $St_2$ couples with that at $St_1$ to induce third-order nonlinear terms, giving rise to a non-monotonic suppression mechanism that smooths out the flame’s spatial wrinkling owing to the positive correlation between $u_c$ and $St$. As a result, excitation at $St_2$ modifies the HRR response at $St_1$, delineating an effective region bounded on the left by the frequency threshold of the linear response and on the right by the aforementioned non-monotonicity. Within this region, excitation at $St_2$ can markedly attenuate the HRR gain at $St_1$ compared with the case where the flame is driven solely by the perturbation at $St_1$. For instance, once both perturbation amplitudes exceed a certain threshold, excitation at $St_2$ can attenuate the flame response at $St_1$ by more than 40 % compared with the case without excitation at $St_2$. These findings contribute to the development of a quantitative framework for understanding how targeted frequency perturbations modulate the flame dynamics via nonlinear interactions, which may inform open-loop approaches for mitigating thermoacoustic instabilities in combustion chambers.

In childhood, diets high in sodium and low in potassium contribute to raised blood pressure and cardiovascular disease later in life(1). For New Zealand (NZ) children, bread is a major source of dietary sodium, and fruit, vegetables, and milk are major dietary sources of potassium(2,3). However, it is mandatory to use iodised salt in NZ bread meaning reducing the salt and thus sodium content could put children at risk of iodine deficiency(4). Our objective was to measure the sodium, potassium, and iodine intake, and blood pressure of NZ school children 8-13 years old. A cross-sectional survey was conducted in five primary schools in Auckland and Dunedin. Primary schools were recruited between July 2022 and February 2023 using purposive sampling. Seventy-five children (n= 37 boys, 29 girls, and nine children who did not state their gender) took part. The most common ethnicity was NZ European and Other (n=54 or 72%) followed by Māori (indigenous inhabitants; n=9 or 12%) and Pasifika (n=5 or 7%). The main outcomes were 24-hour sodium and potassium intake, sodium to potassium molar ratio, 24-hour iodine intake, and BP. Sodium, potassium, and iodine intake were assessed using 24-hour urine samples and BP was assessed using standard methods. Differences by gender were tested using two-sample t-tests and nonparametric Wilcoxon two-sample tests. The mean (SD) 24-hour sodium excretion, potassium excretion, and sodium to potassium molar ratio for children with complete samples (n=59) were 2,420 (1,025) mg, 1,567 (733) mg, and 3.0 (1.6), respectively. The median (25th, 75th percentile) urinary iodine excretion was 88 (61, 122) µg per 24 hours and the mean (SD) systolic and diastolic blood pressure (n=74) were 105 (10) mmHg and 67 (9) mmHg, respectively. There was a significant difference between boys and girls for iodine (77 (43, 96) vs. 98 (72, 127) µg per 24 hours; p=0.02) but no other outcomes. In conclusion, children consumed more sodium and less potassium and iodine than World Health Organization recommendations(5). However, future research should confirm these findings in a nationally representative sample. Evidence-based, equitable interventions and policies with adequate monitoring should be considered to reduce potentially suboptimal sodium, potassium, and iodine intakes in New Zealand.

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.

Background: Antibodies directed against acetylcholine receptor (AChR) are absent in approximately 15% of patients with gMG. Approved treatment options represent an unmet need in the AChR-antibody (Ab)- gMG population. Efgartigimod is an immunoglobulin G1 (IgG1) antibody Fc fragment that selectively reduces IgG levels by blocking neonatal Fc receptor (FcRn)-mediated IgG recycling. Here, we describe efgartigimod efficacy in AChR-Ab- participants with gMG receiving either efgartigimod IV or subcutaneous (SC) efgartigimod PH20 (coformulated with recombinant human hyaluronidase PH20) across clinical studies. Methods: Post hoc analyses were conducted to examine efficacy and safety of efgartigimod IV and/or efgartigimod PH20 SC in AChR-Ab- participants in ADAPT/ADAPT+ and ADAPT-SC/ADAPT-SC+ trials. Results: Among pooled AChR-Ab- participants (n=56), mean (SE) MG-ADL total score improvement from baseline to Week 3 was -3.7 (Cycle 1: 0.44 [n=55]). Consistent MG-ADL improvements occurred with repeated cycles. Clinically meaningful improvements (CMI; ≥2-point MG-ADL decrease) occurred in 76.4% (n=42/55) of participants (Cycle 1, Week 3). In Cycle 1, 23.2% (n=13/56) of participants achieved minimal symptom expression (MG-ADL 0-1). Similar efficacy results occurred across all cycles. Overall safety profile was similar between AChR-Ab+ and AChR-Ab- participants. Conclusions: Both efgartigimod IV and efgartigimod PH20 SC were well tolerated and led to CMI in participants with AChR-Ab- gMG.

Lactoferrin (LF), a sialylated iron-binding glycoprotein consisting of multiple sialic acid (Sia) residues attached to N-linked glycan chains, and studies have shown that both the iron and Sia are crucial for early neurodevelopment and cognition.(1) However, there is limited knowledge of the impacts of the iron saturation and sialylation in LF molecule on the early neurodevelopment and cognition. Objectives of the study were to explore the impacts and mechanisms of iron saturation and sialylation in LF molecule on early neurodevelopment and cognition. Maternal dietary intervention with native bovine LF (Native-LF), iron-free bovine LF (Apo-LF), or Sia-free bovine LF (Desia-LF) at a dose of 0.60 g/kg body weight per day was administered throughout the lactation period. Offspring pups were assessed for anxiety, learning, and memory through behavioral tests before being euthanized on postnatal day 63. Brain hippocampal tissue was then analyzed for polysialic acid (polySia), a marker of neurodevelopment and neuroplasticity.(1) The study protocol was approved by the Xiamen University Animal Ethics Committee (AE1640102). Our results showed that Apo-LF pups exhibited a 1.32-fold increase in total distance travelled in the arena compared to both Native-LF and Desia-LF groups, with the overall difference among the groups being statistically significant in the open field test (p = 0.008). Additionally, the frequency of central area entries in the Apo-LF group was 2.00-fold higher than in Desia-LF pups (p = 0.038) and 1.3-fold higher than in Native-LF pups, with a significant overall difference (p = 0.042). No significant differences in total distance travelled or central area entries were observed between Native-LF and Desia-LF groups (p > 0.05). These results suggest that Apo-LF pups demonstrated better anti-anxiety behaviors than both Native-LF and Desia-LF pups. In the Morris water maze test, Apo-LF pups spent significantly more time in the target quadrant compared to both Desia-LF (p = 0.019) and Native-LF pups (p = 0.0009), indicating enhanced short-term memory. Additionally, Apo-LF pups exhibited greater polySia-NCAM expression (1.2.95 ± 0.048) in the hippocampus, a marker associated with neuroplasticity and neurogenesis compared to both Native-LF and Desia-LF pups. We conclude that maternal supplementation with different types of lactoferrin during lactation supports improved learning and memory in offspring through distinct mechanisms, with sialylation playing a crucial role in neurocognitive development.

We study household fuel choice in rural China through the lens of social interactions, deploying a structural discrete choice interaction model to explain peer-dependence in household fuel choice. The data comes from the China Family Panel Studies 2010–2020, and we use multiple strategies to examine the robustness of the social interaction effects. We find a significant endogenous social effect, meaning that whether a household chooses non-solid clean fuel for cooking is directly affected by the choice in cooking fuel made by its neighbors in the village. Households with lower non-farm income are more sensitive to the choices of others, and the fuel choices of households with a higher education and/or a higher income attracts more attention from others. Modern communication technologies facilitate information exchange among rural residents, thereby strengthening the endogenous social effect. We suggest that public policies can accelerate rural energy transition by stimulating positive social spillovers.

Objectives: Leveraging the non-monolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia risk in Latin American populations

Methods: Community-dwelling participants aged 65 and older (N = 3808) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. The primary outcome measured was the risk of developing dementia. Multivariate linear regression models adjusted for SDoH were used in the main analysis.

Results: We observed extensive three-way (African/European/Native American) genetic ancestry variation between countries. Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p <0.001), lower SES (p < 0.001), and higher frequency of vascular risk factors (p < 0.001). In unadjusted analysis, American individuals with predominant African ancestry exhibited a higher dementia frequency (p = 0.03) and both Native and African ancestry predominant groups showed lower cognitive performance relative to those with higher European ancestry (p < 0.001). However, after adjusting for measures of SDoH, there was no association between ancestry proportion and dementia probability, and ancestry proportions no longer significantly accounted for the variance in cognitive performance (African predominant p = 0.31 [–0.19, 0.59] and Native predominant p = 0.74 [–0.24, 0.33]).

Conclusions: The findings suggest that social and environmental factors play a more crucial role than genetic ancestry in predicting dementia risk in Latin American populations. This underscores the need for public health strategies and policies that address these social determinants to reduce dementia risk in these communities effectively.

Unhealthy food environments are major drivers of obesity and diet-related diseases(1). Improving the healthiness of food environments requires a widespread organised response from governments, civil society, and industry(2). However, current actions often rely on voluntary participation by industry, such as opt-in nutrition labelling schemes, school/workplace food guidelines, and food reformulation programmes. The aim of the REFORM study is to determine the effects of the provision of tailored support to companies on their nutrition-related policies and practices, compared to food companies that are not offered the programme (the control). REFORM is a two-country, parallel cluster randomised controlled trial. 150 food companies were randomly assigned (2:1 ratio) to receive either a tailored support intervention programme or no intervention. Randomisation was stratified by country (Australia, New Zealand), industry sector (fast food, other packaged food/beverage companies), and company size. The primary outcome is the nutrient profile (measured using Health Star Rating [HSR]) of foods and drinks produced by participating companies at 24 months post-baseline. Secondary outcomes include company nutrition policies and commitments, the nutrient content (sodium, sugar, saturated fat) of products produced by participating companies, display of HSR labels, and engagement with the intervention. Eighty-three eligible intervention companies were invited to take part in the REFORM programme and 21 (25%) accepted and were enrolled. Over 100 meetings were held with company representatives between September 2021 and December 2022. Resources and tailored reports were developed for 6 touchpoints covering product composition and benchmarking, nutrition labelling, consumer insights, nutrition policies, and incentives for companies to act on nutrition. Detailed information on programme resources and preliminary 12-month findings will be presented at the conference. The REFORM programme will assess if provision of tailored support to companies on their nutrition-related policies and practices incentivises the food industry to improve their nutrition policies and actions.

OBJECTIVES/GOALS: The correction of spinopelvic parameters is associated with better outcomes in patients with adult spinal deformity (ASD). This study presents a novel artificial intelligence (AI) tool that automatically predicts spinopelvic parameters from spine x-rays with high accuracy and without need for any manual entry. METHODS/STUDY POPULATION: The AI model was trained/validated on 761 sagittal whole-spine x-rays to predict the following parameters: Sagittal Vertical Axis (SVA), Pelvic Tilt (PT), Pelvic Incidence (PI), Sacral Slope (SS), Lumbar Lordosis (LL), T1-Pelvic Angle (T1PA), and L1-Pelvic Angle (L1PA). A separate test set of 40 x-rays was labeled by 4 reviewers including fellowship-trained spine surgeons and a neuroradiologist. Median errors relative to the most senior reviewer were calculated to determine model accuracy on test and cropped-test (i.e. lumbosacral) images. Intraclass correlation coefficients (ICC) were used to assess inter-rater reliability RESULTS/ANTICIPATED RESULTS: The AI model exhibited the following median (IQR) parameter errors: SVA[2.1mm (8.5mm), p=0.97], PT [1.5° (1.4°), p=0.52], PI[2.3° (2.4°), p=0.27], SS[1.7° (2.2°), p=0.64], LL [2.6° (4.0°), p=0.89], T1PA [1.3° (1.1°), p=0.41], and L1PA [1.3° (1.2°), p=0.51]. The parameter errors on cropped lumbosacral images were: LL[2.9° (2.6°), p=0.80] and SS[1.9° (2.2°), p=0.78]. The AI model exhibited excellent reliability at all parameters in both whole-spine (ICC: 0.92-1.0) and lumbosacral x-rays: (ICC: 0.92-0.93). DISCUSSION/SIGNIFICANCE: Our AI model accurately predicts spinopelvic parameters with excellent reliability comparable to fellowship-trained spine surgeons and neuroradiologists. Utilization of predictive AI tools in spine-imaging can substantially aid in patient selection and surgical planning.

This study advances a coopetition perspective to argue that an intangibility gap, defined as the difference in intangible asset intensity between industry-frontier foreign firms and local firms, generates both competitive threats and cooperative opportunities for local firms. Thus, an intangibility gap may affect local firms’ internal research and development (R&D) efforts beyond a linear, catching-up way of thinking. Using a sample of manufacturing firms in China, we find that intangibility gap has an inverted U-shaped relationship with the internal R&D intensity of local firms such that a moderate intangibility gap is more likely to stimulate local firms’ R&D than a small or large intangibility gap. Moreover, the results show that export intensity and state ownership of local firms serve as two boundary conditions under which the inverted U-shaped relationship becomes less and more pronounced, respectively.