Background: Considering regional and temporal trends, we sought to explore the incidence of primary malignant brain tumours in Newfoundland and Labrador. Methods: We reviewed all primary, malignant brain tumour cases from 2015-2022 confirmed by St. John’s Health Sciences Centre pathology reports. Incidence rates were standardized using the 2011 Canadian standard population. Results: We included 362 cases. The average annual age-standardized incidence rate of primary, malignant brain tumours per 100,000 was 7.0 (95% CI: 6.3-7.7), lower than the national average (7.93; 95% CI: 7.78-8.08). The incidence of glioblastoma (5.1; 95% CI: 4.5-5.7) was significantly higher than the national average (4.05; 95% CI: 3.95-4.16). Temporal trends revealed that oligodendroglioma incidence spiked from 0.5 (95% CI: 0.2-0.7) in 2015-2019 to 1.5 (95% CI: 0.4-2.6) in 2020 before returning to baseline in 2022. Regional trends indicated a lower incidence of malignant tumours in Labrador-Grenfell (5.1; 95% CI: 2.5-7.6), compared to 6.9 (95% CI: 6.2-7.6) averaged elsewhere. Conclusions: Higher rates of glioblastoma in Newfoundland and Labrador could have a genetic or multi-factorial cause. The increased occurrence of oligodendroglioma during the COVID-19 pandemic necessitates broader investigation, potentially linked to delays in patient care during this period. Regional trends could suggest less access to care in rural populations and underestimated incidence.

Background: Brain metastases indicate an advanced tumour stage for many cancers. We sought to investigate the incidence change of tissue-sampled brain metastases and its relation to staging challenges during the COVID-19 pandemic in Newfoundland and Labrador. Methods: We reviewed all brain metastasis cases from 2015-2022 requiring first-time tissue sampling according to pathology reports from the St. John’s Health Sciences Centre. Incidence rates were calculated using yearly population data by regional health authorities and standardized using the 2011 Canadian standard population. Results: We included 173 cases. The average annual age-standardized incidence rate of brain metastases requiring tissue sampling per 100,000 increased from 2.5 (95% CI: 2.0-3.1) pre-COVID-19 to 4.1 (95% CI: 3.3-5.0) post-COVID-19. Brain metastases from lung primaries accounted for 69% of this increase. While incidence declined to near-baseline in the Eastern provincial population by 2022 (3.3; 95% CI: 1.5-5.1), incidence rose into 2022 in the Western population (8.6; 95% CI: 3.9-13.2). Conclusions: These data suggest a delayed presentation of malignancies during the COVID-19 pandemic and underscore the importance of prioritized staging during times of strain on healthcare systems. Regional, temporal trends suggest regions distant from tertiary care centres could face challenges in resolving cases with delayed presentation post-COVID-19.

OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the ‘molecular tumour board’ into ‘standard of care’ ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.

While socioeconomic disparities in the home language environment have been well established, the mechanisms explaining these disparities are poorly understood. One plausible mechanism is heightened stress. The current study investigated whether maternal perceived stress was 1) associated with measures of the home language environment, and 2) mediated the relation between socioeconomic disparities and the home language environment. Data from three independent studies were analyzed, which together comprised 322 mother-child dyads. Two studies included mothers and their six- to twelve-month-old infants (N = 227). The third included mothers and their five- to nine-year-old children (N = 95). Mothers reported their educational attainment, income, and stress. Language Environment Analysis (LENA) measured the home language environment. As has been previously reported, socioeconomic disparities were observed in adult words and conversational turns. Stress did not mediate these associations, nor was it associated with adult words or conversational turns. Alternate mechanisms for future exploration are discussed.

Stress has been linked with children’s socioemotional problems and lower language scores, particularly among children raised in socioeconomically disadvantaged circumstances. Much of the work examining the relations among stress, language, and socioemotional functioning have relied on assessments of a single dimension of maternal stress. However, stress can stem from different sources, and people may appraise stressors differently. Taking a dimensional approach, this manuscript characterizes stress in multiple ways: as an overall composite; across the constructs of psychological appraisal vs. environmental stressors; and the independent contributions of a variety assessments. Data are from 548 mother–infant dyads (M = 13.14 months, SD = 2.11) who served as the control group for a poverty reduction clinical trial. Mothers completed questionnaires regarding the different types of stresses they may have experienced, as well as their children’s language and socioemotional development. Results indicate that, collectively, higher maternal report of stress is associated with lower reports of children’s socioemotional and language development. In addition, maternal psychological appraisals of stress were associated with both socioemotional and language development, whereas reports of environmental stressors were only associated with socioemotional development. Together, these findings suggest that maternal reports of stress are associated with lower maternal report of child development among low-income children.

The name of the genus Lycium originates from the Greek name lykion for a thorny shrub, derived from Lycia, the name of an ancient country in Asia Minor where a similar spiny shrub was found. The specific epithet ferocissimum comes from the Latin ferox, meaning “bold” or “fearless,” referring to the very spiny nature of the shrub (Green 1994; Parsons and Cuthbertson 2001).

Arctic mining has a bad reputation because the extractive industry is often responsible for a suite of environmental problems. Yet, few studies explore the gap between untouched tundra and messy megaproject from a historical perspective. Our paper focuses on Advent City as a case study of the emergence of coal mining in Svalbard (Norway) coupled with the onset of mining-related environmental change. After short but intensive human activity (1904–1908), the ecosystem had a century to respond, and we observe a lasting impact on the flora in particular. With interdisciplinary contributions from historical archaeology, archaeozoology, archaeobotany and botany, supplemented by stable isotope analysis, we examine 1) which human activities initially asserted pressure on the Arctic environment, 2) whether the miners at Advent City were “eco-conscious,” for example whether they showed concern for the environment and 3) how the local ecosystem reacted after mine closure and site abandonment. Among the remains of typical mining infrastructure, we prioritised localities that revealed the subtleties of long-term anthropogenic impact. Significant pressure resulted from landscape modifications, the import of non-native animals and plants, hunting and fowling, and the indiscriminate disposal of waste material. Where it was possible to identify individual inhabitants, these shared an economic attitude of waste not, want not, but they did not hold the environment in high regard. Ground clearances, animal dung and waste dumps continue to have an effect after a hundred years. The anthropogenic interference with the fell field led to habitat creation, especially for vascular plants. The vegetation cover and biodiversity were high, but we recorded no exotic or threatened plant species. Impacted localities generally showed a reduction of the natural patchiness of plant communities, and highly eutrophic conditions were unsuitable for liverworts and lichens. Supplementary isotopic analysis of animal bones added data to the marine reservoir offset in Svalbard underlining the far-reaching potential of our multi-proxy approach. We conclude that although damaging human–environment interactions formerly took place at Advent City, these were limited and primarily left the visual impact of the ruins. The fell field is such a dynamic area that the subtle anthropogenic effects on the local tundra may soon be lost. The fauna and flora may not recover to what they were before the miners arrived, but they will continue to respond to new post-industrial circumstances.

Recent work in structure–processing relationships of polymer semiconductors have demonstrated the versatility and control of thin-film microstructure offered by meniscus-guided coating (MGC) techniques. Here, we analyze the qualitative and quantitative aspects of solution shearing, a model MGC method, using coating blades augmented with arrays of pillars. The pillars induce local regions of high strain rates—both shear and extensional—not otherwise possible with unmodified blades, and we use fluid mechanical simulations to model and study a variety of pillar spacings and densities. We then perform a statistical analysis of 130 simulation variables to find correlations with three dependent variables of interest: thin-film degree of crystallinity and transistor field-effect mobilities for charge-transport parallel (μpara) and perpendicular (μperp) to the coating direction. Our study suggests that simple fluid mechanical models can reproduce substantive correlations between the induced fluid flow and important performance metrics, providing a methodology for optimizing blade design.

Background: Peritoneal dialysis is a type of dialysis performed by patients in their homes; patients receive training from dialysis clinic staff. Peritonitis is a serious complication of peritoneal dialysis, most commonly caused by gram-positive organisms. During March‒April 2019, a dialysis provider organization transitioned ~400 patients to a different manufacturer of peritoneal dialysis equipment and supplies (from product A to B). Shortly thereafter, patients experienced an increase in peritonitis episodes, caused predominantly by gram-negative organisms. In May 2019, we initiated an investigation to determine the source. Methods: We conducted case finding, reviewed medical records, observed peritoneal dialysis procedures and trainings, and performed patient home visits and interviews. A 1:1 matched case–control study was performed in 1 state. A case had ≥2 of the following: (1) positive peritoneal fluid culture, (2) high peritoneal fluid white cell count with ≥50% polymorphonuclear cells, or (3) cloudy peritoneal fluid and/or abdominal pain. Controls were matched to cases by week of clinic visit. Conditional logistic regression was used to estimate univariate matched odds ratios (mOR) and 95% confidence intervals (CIs). We conducted microbiological testing of peritoneal dialysis fluid bags to rule out product contamination. Results: During March‒September 2019, we identified 157 cases of peritonitis across 15 clinics in 2 states (attack rate≍39%). Staphylococcus spp (14%), Serratia spp (12%) and Klebsiella spp (6.3%) were the most common pathogens. Steps to perform peritoneal dialysis using product B differed from product A in several key areas; however, no common errors in practice were identified to explain the outbreak. Patient training on transitioning products was not standardized. Outcomes of the 73 cases in the case–control study included hospitalization (77%), peritoneal dialysis failure (40%), and death (7%). The median duration of training prior to product transition was 1 day for cases and controls (P = .86). Transitioning to product B (mOR, 18.00; 95% CI, 2.40‒134.83), using product B (mOR, 18.26; 95% CI, 3.86‒∞), drain-line reuse (mOR, 4.67; 95% CI, 1.34‒16.24) and performing daytime exchanges (mOR, 3.63; 95% CI, 1.71‒8.45) were associated with peritonitis. After several interventions, including transition of patients back to product A (Fig. 1), overall cases declined. Sterility testing of samples from 23 unopened product B peritoneal dialysis solution bags showed no contamination. Conclusions: Multiple factors may have contributed to this large outbreak, including a rapid transition in peritoneal dialysis products and potentially inadequate patient training. Efforts are needed to identify and incorporate best training practices, and product advances are desired to improve the safety of patient transitions between different types of peritoneal dialysis equipment.

Funding: None

Disclosures: None

This paper discusses the evidence for periodic human activity in the Cairngorm Mountains of Scotland from the late 9th millennium to the early 4th millennium cal bc. While contemporary paradigms for Mesolithic Europe acknowledge the significance of upland environments, the archaeological record for these areas is not yet as robust as that for the lowland zone. Results of excavation at Chest of Dee, along the headwaters of the River Dee, are set into a wider context with previously published excavations in the area. A variety of site types evidences a sophisticated relationship between people and a dynamic landscape through a period of changing climate. Archaeological benefits of the project include the ability to examine novel aspects of the archaeology leading to a more comprehensive understanding of Mesolithic lifeways. It also offers important lessons in site survival, archaeological investigation, and the management of the upland zone.

X-ray powder diffraction patterns of kaolinites have been studied with especial reference to the region of the 02, 11, band. Satisfactory correlations with calculated patterns based on the layer structure of dickite can be achieved for a range of kaolinites if account is taken of disorder between and within layers. Some indication of the amount of disorder within a kaolinite can be obtained.

Little is known about terrestrial climate dynamics in the Levant during the penultimate interglacial-glacial period. To decipher the palaeoclimatic history of the Marine Oxygen Isotope Stage (MIS) 6 glacial period, a well-dated stalagmite (~194 to ~154 ka) from Kanaan Cave on the Mediterranean coast in Lebanon was analyzed for its petrography, growth history, and stable isotope geochemistry. A resolved climate record has been recovered from this precisely U–Th dated speleothem, spanning the late MIS 7 and early MIS 6 at low resolution and the mid–MIS 6 at higher resolution. The stalagmite grew discontinuously from ~194 to ~163 ka. More consistent growth and higher growth rates between ~163 and ~154 ka are most probably linked to increased water recharge and thus more humid conditions. More distinct layering in the upper part of the speleothem suggests strong seasonality from ~163 ka to ~154 ka. Short-term oxygen and carbon isotope excursions were found between ~155 and ~163 ka. The inferred Kanaan Cave humid intervals during the mid–MIS 6 follow variations of pollen records in the Mediterranean basins and correlate well with the synthetic Greenland record and East Asian summer monsoon interstadial periods, indicating short warm/wet periods similar to the Dansgaard-Oeschger events during MIS 4–3 in the eastern Mediterranean region.

Vaccination remains a mainstay of companion animal population health. However, how vaccine use at a population level complies with existing guidelines is unknown. Here we use electronic health records to describe vaccination in dogs, cats and rabbits attending a large sentinel network of UK veterinary practices. In total, 77.9% (95% CI: 77.6–78.1) of animals had recorded vaccinations. The percentage of animals with recorded vaccinations was higher in dogs, neutered animals, in insured dogs and cats and in purebred dogs. Vaccination rates varied in different regions of Great Britain in all species. Dogs and cats belonging to owners living in less deprived areas of England and Scotland were more likely to be recorded as vaccinated. In the vaccinated population, cats received more core vaccines per year of life (0.86) than dogs (0.75), with feline leukaemia vaccines almost as frequent as core vaccines. In dogs, leptospira vaccines were more frequent than core vaccines. This descriptive study suggests a substantial proportion of animals are not benefiting from vaccine protection. For the first time, we identify potential factors associated with variations in recorded vaccination frequency, providing a critical baseline against which to monitor future changes in companion animal vaccination and evidence to inform future targeted health interventions.

Introduction: Point of care ultrasound (PoCUS) has become an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). Current established protocols (e.g. RUSH and ACES) were developed by expert user opinion, rather than objective, prospective data. Recently the SHoC Protocol was published, recommending 3 core scans; cardiac, lung, and IVC; plus other scans when indicated clinically. We report the abnormal ultrasound findings from our international multicenter randomized controlled trial, to assess if the recommended 3 core SHoC protocol scans were chosen appropriately for this population. Methods: Recruitment occurred at seven centres in North America (4) and South Africa (3). Screening at triage identified patients (SBP<100 or shock index>1) who were randomized to PoCUS or control (standard care with no PoCUS) groups. All scans were performed by PoCUS-trained physicians within one hour of arrival in the ED. Demographics, clinical details and study findings were collected prospectively. A threshold incidence for positive findings of 10% was established as significant for the purposes of assessing the appropriateness of the core recommendations. Results: 138 patients had a PoCUS screen completed. All patients had cardiac, lung, IVC, aorta, abdominal, and pelvic scans. Reported abnormal findings included hyperdynamic LV function (59; 43%); small collapsing IVC (46; 33%); pericardial effusion (24; 17%); pleural fluid (19; 14%); hypodynamic LV function (15; 11%); large poorly collapsing IVC (13; 9%); peritoneal fluid (13; 9%); and aortic aneurysm (5; 4%). Conclusion: The 3 core SHoC Protocol recommendations included appropriate scans to detect all pathologies recorded at a rate of greater than 10 percent. The 3 most frequent findings were cardiac and IVC abnormalities, followed by lung. It is noted that peritoneal fluid was seen at a rate of 9%. Aortic aneurysms were rare. This data from the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients, supports the use of the prioritized SHoC protocol, though a larger study is required to confirm these findings.