The effect dietary FODMAPs (fermentable oligo-, di- and mono-saccharides and polyols) in healthy adults is poorly documented. This study compared specific effects of low and moderate FODMAP intake (relative to typical intake) on the faecal microbiome, participant-reported outcomes and gastrointestinal physiology. In a single-blind cross-over study, 25 healthy participants were randomised to one of two provided diets, ‘low’ (LFD) <4 g/d or ‘moderate’ (MFD) 14-18 g/d, for 3 weeks each, with ≥2-week washout between. Endpoints were assessed in the last week of each diet. The faecal bacterial/archaeal and fungal communities were characterised in 18 participants in whom high quality DNA was extracted by 16S rRNA and ITS2 profiling, and by metagenomic sequencing. There were no differences in gastrointestinal or behavioural symptoms (fatigue, depression, anxiety), or in faecal characteristics and biochemistry (including short-chain fatty acids). Mean colonic transit time (telemetry) was 23 (95% confidence interval: 15, 30) h with the MFD compared with 34 (24, 44) h with LFD (n=12; p=0.009). Fungal diversity (richness) increased in response to MFD, but bacterial richness was reduced, coincident with expansion of the relative abundances of Bifidobacterium, Anaerostipes, and Eubacterium. Metagenomic analysis showed expansion of polyol-utilising Bifidobacteria, and Anaerostipes with MFD. In conclusion, short-term alterations of FODMAP intake are not associated with symptomatic, stool or behavioural manifestations in healthy adults, but remarkable shifts within the bacterial and mycobiome populations were observed. These findings emphasise the need to quantitatively assess all microbial Domains and their interrelationships to improve understanding of consequences of diet on gut function.

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.

OBJECTIVES/GOALS: This study examined patient perceptions on the benefits, barriers, and facilitators of conventional and complementary/behavioral pain strategies that can be offered in the ED setting including physical therapy, mindfulness, acupuncture, and yoga. METHODS/STUDY POPULATION: We conducted and recorded semi-structured interviews with 30 patients who presented to the ED with musculoskeletal pain. Interviews focused on patients’ perceptions of NP pain treatments, barriers/facilitators to utilization, and recommendations that would promote engagement. A hierarchical coding system was developed and refined using the interview guide, the Theory of Planned Behavior, and preliminary review of the transcripts. The iterative process of developing the coding system allowed us to identify preliminary themes. RESULTS/ANTICIPATED RESULTS: Patients believe education on pain and the mind-body connection would give a sense of pain control. Likely barriers to engaging at the ED include lights, noise, interruptions, and uncertainty of their medical status. Post-discharge NP treatment barriers are financial and logistical. Engagement can be facilitated by a desire to avoid opioids, familiarity with meditation practices, and consistent positive communication with the health care team. Patients desire evidence on effectiveness, including testimonials, and suggested NP techniques should be introduced early, with written materials used for post-discharge referral. Patients prefer in-person treatment but would appreciate a virtual option. The initial session should occur in-person to build trust and facilitate virtual session engagement. DISCUSSION/SIGNIFICANCE: Patients are willing to engage in nonpharmacological pain treatment, however the unpredictable ED environment, uncertainty of their medical status, and financial and time constraints are significant barriers.

Energetic-particle-induced geodesic acoustic modes, EGAMs (Fu, Phys. Rev. Let., vol. 101, 2008, pp. 185002), driven by neutral beam injection (NBI), have been observed in many DIII-D tokamak experiments (Nazikian et al., Phys. Rev. Lett., vol. 101, 2008, pp. 185001). This mechanism has been theoretically investigated in (Qiu et al., Plasma Phys. Control. Fusion, vol. 52, 2010, pp. 095003), using a sharp energetic particle distribution function, and in (Qu et al., Plasma Phys. Control. Fusion, vol. 59, 2017, pp. 055018), where the dispersion relation and eigenmode behaviour were obtained for the situation of early beam scenario, that is, for times smaller than the beam slowing down time. In this work, we extend these studies determining the eigenmode for beyond the slowing down time, in a scenario with reverse safety factor $q$ profile, where a small concentration of energetic ions can produce an off-axis maximum in the GAM dispersion relation. The characteristics of EGAM are analytically studied with the drift kinetic equation together with the MHD code NOVA. The toroidal energetic ion transit frequency, coupled with the GAM frequency, produces the maximum in the dispersion relation where the eigenmode can be found. The quantitative correspondence of experimental results with the predictions of the proposed model is analysed.

The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.

The role of the Eurasian badger (Meles meles) as a wildlife host has complicated the management of bovine tuberculosis (bTB) in cattle. Badger ranging behaviour has previously been found to be altered by culling of badgers and has been suggested to increase the transmission of bTB either among badgers or between badgers and cattle. In 2014, a five-year bTB intervention research project in a 100 km2 area in Northern Ireland was initiated involving selective removal of dual path platform (DPP) VetTB (immunoassay) test positive badgers and vaccination followed by release of DPP test negative badgers (‘Test and Vaccinate or Remove’). Home range sizes, based on position data obtained from global positioning system collared badgers, were compared between the first year of the project, where no DPP test positive badgers were removed, and follow-up years 2–4 when DPP test positive badgers were removed. A total of 105 individual badgers were followed over 21 200 collar tracking nights. Using multivariable analyses, neither annual nor monthly home ranges differed significantly in size between years, suggesting they were not significantly altered by the bTB intervention that was applied in the study area.

The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.

Over half of the Irish population is overweight or obese. The Obesity Policy and Action Plan 2016–2025 will set reformulation targets for fat, saturated fat and sugar in Ireland and review progress. In 2016, the Food Safety Authority of Ireland undertook a cross-sectional market scan of yoghurts to evaluate the energy, fat, saturated fat and sugar content based solely on declared nutrition labels. The aims of this 2018 study were to verify the accuracy of declared nutrition information on yoghurts and to confirm the suitability of declared nutrition labels for energy, fat, saturated fat and sugar reformulation monitoring.

Yoghurts identified in the 2016 market scan (n578) were weighted based on categorisation of manufacturer type (branded, own brand), product category (natural, flavoured and luxury) and declared nutrition content. Samples (n200) were randomly selected from these weighted groups and tested by a laboratory accredited for energy, fat, saturated fat, and sugar analysis. Data was analysed using IBM SPSS (version25). As data was not normally distributed, median values were investigated for declared and tested energy, fat, saturated fat and sugar content using Wilcoxon Signed-Rank Test and Spearman Rank-Order Correlation.

Of the tested yoghurts, 3% (n6), 5% (n9) and 19% (n31) were outside the recommended European Commission (EC) labelling tolerance for fat, saturated fat and sugar, respectively. Tested nutrient content was consistently lower than declared. There was a statistically significant difference in declared vs. tested energy (87kcal vs. 84kcal p = 0.03), fat (2.7 g vs. 2.5 g p < 0.001), and sugar (9.9 g vs. 8.7 g p < 0.001) content per 100 g yoghurt. Declared vs. tested sugar content per 100 g yoghurt was statistically significant across all yoghurt types, including natural (4.8 g vs. 3.4 g p < 0.001), flavoured (9.7 g vs. 8.6 g p < 0.001) and luxury (15 g vs. 13.6 g p = 0.002). There was a statistically significant difference between declared vs. tested fat (2.8 g vs. 2.5 g p < 0.001) and saturated fat (1.9 g vs.1.6 g p = 0.017) content of own brand yoghurts per 100 g. There was a positive correlation between energy content and portion size (r = .2,p < 0.01).

There was a high level of agreement between declared vs. tested fat and saturated fat content of yoghurts, but a lower level of agreement between declared vs. tested sugar content of yoghurts. This indicates that declared nutrition labels are suitable for reformulation monitoring of fat and saturated fat, but may not be suitable for sugar. This finding will be further investigated and tested in future work planned for nutrition label verification of other food categories.

Objectives: Youth and young adults with pediatric-onset multiple sclerosis (MS) are vulnerable to executive dysfunction; however, some patients do not demonstrate functional deficits despite showing abnormalities on structural magnetic resonance imaging (MRI). Cognitively intact adults with MS have shown enhanced activation patterns relative to healthy controls on working memory tasks. We aim to evaluate whether cognitively preserved pediatric-onset MS patients engage compensatory recruitment strategies to facilitate age-normative performance on a task of working memory. Methods: Twenty cognitively preserved patients (mean age=18.7±2.7 years; 15 female) and 20 age- and sex-matched controls (mean age=18.5±2.9 years; 15 female) underwent neuropsychological testing and 3.0 Tesla MRI, including structural and functional acquisitions. Patterns of activation during the Alphaspan task, a working memory paradigm with two levels of executive control demand, were examined via whole-brain and region of interest (ROI) analyses. Results: Across all participants, lower accuracy and greater activation of regions implicated in working memory were observed during the high demand condition. MS patients demonstrated 0.21 s longer response time than controls. ROI analyses revealed enhanced activation for pediatric-onset MS patients relative to controls in the right middle frontal, left paracingulate, right supramarginal, and left superior parietal gyri during the low executive demand condition, over and above differences in response time. MS patients also demonstrated heightened activation in the right supramarginal gyrus in the high executive demand condition. Conclusions: Our findings suggest that pediatric-onset MS patients may engage compensatory recruitment strategies during working memory processing. (JINS, 2019, 25, 432–442)