Wake characteristics of tall buildings in a realistic urban Canopy

The presence of tall buildings in cities affects momentum and scalar exchange within and above the urban canopy. As wake effects can be important over large distances, they are crucial for urban-flow modelling on and across different spatial scales. We explore the aerodynamic effects of tall buildings on the microscale to local scales with a focus on the interaction between the wake structure, canopy and roughness sublayer (RSL) flow of the surroundings in a realistic urban setting in central London. Flow experiments in a boundary-layer wind tunnel use a 1:200 scale model with two tall buildings (81 m and 134.3 m) for two wind directions. Large changes in mean flow, turbulence statistics and instantaneous flow structure of the wake are evident when tall buildings are part of the complex urban canopy rather than isolated. In the near–wake, the presence of lower buildings displaces the core of the recirculation zone upwards, thereby reducing the vertical depth over which flow reversal occurs. This amplifies vertical shear at the rooftop and enhances turbulent momentum exchange. In the near part of the main–wake, lateral velocity fluctuations and hence turbulence kinetic energy are reduced compared to the isolated building case as eddies generated in the urban canopy and RSL distribute energy down to smaller scales that dissipate more rapidly. Evaluation of a wake model for flow past isolated buildings suggests model refinements are needed to account for such flow-structure changes in tall-building canopies

Optically guided linear Mach-Zehnder atom interferometer

We demonstrate a horizontal, linearly guided Mach-Zehnder atom interferometer in an optical waveguide. Intended as a proof-of-principle experiment, the interferometer utilizes a Bose-Einstein condensate in the magnetically insensitive F=1,mF=0 state of 87Rb as an acceleration-sensitive test mass. We achieve a modest sensitivity to acceleration of Δa=7×10-4 m/s2. Our fringe visibility is as high as 38% in this optically guided atom interferometer. We observe a time of flight in the waveguide of over 0.5 s, demonstrating the utility of our optical guide for future sensors

Social Housing Leads to Increased Ethanol Intake in Male Mice Housed in Environmentally Enriched Cages

An individual's social environment affects alcohol intake. However, the complex interactions between social context and alcohol intake remain understudied in preclinical models. In the present study, we sought to characterize the effects of social housing on voluntary ethanol intake in male C567BL/6J mice using a continuous access two-bottle choice model. This was accomplished using HM2 cages, which allow for the continuous monitoring of individuals' fluid intake through radiofrequency tracking while they remain undisturbed in a group setting. These cages are moderately environmentally enriched compared to standard shoebox cages. By analyzing the levels of voluntary ethanol intake between socially- and individually-housed mice in HM2 cages, we were able to parse apart the effects of environmental enrichment vs. social enrichment. We found that while intake levels were overall lower than those observed when animals are singly housed in standard shoebox cages, socially-housed males consumed significantly more ethanol compared to individually-housed mice, suggesting that while environmental enrichment attenuates ethanol intake, social enrichment may, in fact, potentiate it. This effect was not specific for alcohol, however, in that ethanol preference did not differ as a product of social context. We also found that the total number of non-consummatory channel entries were consistently higher in individually-housed mice. Additionally, a single corticotropin releasing factor receptor 1 antagonist treatment significantly decreased both water and ethanol intake in socially- and individually-housed mice up to 3 h post-treatment, though the effect on water intake was longer lasting. This treatment also significantly decreased the number of non-consummatory channel entries in individually-housed mice, but not in socially-housed mice, suggesting that increased channel visits may be a stress-related behavior. Lastly, we examined blood ethanol concentrations and FosB immunoreactivity to characterize the physiological responses to ethanol intake in socially- and individually-housed mice. The number of FosB-positive cells in the centrally-projecting Edinger-Westphal nucleus and nucleus accumbens shell positively correlated with average baseline ethanol intake in individually-housed mice, but not in socially-housed mice. Overall, we found that social, but not environmental, enrichment can increase ethanol intake in male C57BL/6J mice. Future studies need to test this phenomenon in female mice and assess the generalizability of this finding

Biological sex influences antibody responses to routine vaccinations in the first year of life

AIM: We investigated the effect of early-life factors, namely sex, delivery mode, feeding method and antibiotic exposure, on antibody responses to routine vaccinations administered during the first year of life. METHODS: One and seven months after the primary course of routine vaccines and 1 month after routine vaccines at 12 months of age, antibodies against 26 vaccine antigens were measured in 398 healthy infants. The geometric mean concentration (GMC) of antibodies (adjusted for effect modifiers with multiple linear regression) and the seroprotection rate for each vaccine were compared for each early-life factor. RESULTS: Sex had an influence on GMCs. Antibody concentrations were significantly lower at 7 months of age in females for tetanus and filamentous haemagglutinin and at 13 months of age for pertactin. In contrast, at 13 months of age, antibody concentrations were significantly higher in females for polio type 3, pneumococcal serotype 6A and measles. Sex did not have an influence on seroprotection rates. Delivery mode, feeding method and antibiotic exposure did not exert a substantial influence on vaccine antibody concentrations. CONCLUSION: There is a difference between males and females in the humoral response to routine vaccinations in the first year of life

Co-design of a digital 24-hour time-use intervention with older adults and allied health professionals

Using co-design principles based on the Health CASCADE framework, we aimed to describe the collaborative process undertaken to develop a 24-hour time-use intervention, called Small Steps, which promoted gradual and incremental health-behavior change. A secondary aim was to reflect on the challenges and benefits of co-design in this project, offering insights into the “why” and “how” to co-design 24-hour time-use interventions with priority populations. Twelve participants were invited and participated in 6 co-design workshops (June 2023–January 2024). To prioritize older adults’ views in the end-product, 8 adults aged >65 years (the target population) and 4 allied health professionals with >2 years’ experience working with the target population were recruited. Workshops and activities were structured using the British Design Council's Double Diamond Design Process to stimulate design thinking. Where possible, participant-led documentation was used to reduce the bias associated with academic scribing and empower participants to provide input and facilitate ownership for the project. Workshop activities and discussions were captured through printouts, audio and iPad screen recordings and analyzed through reflexive thematic and content analysis. Co-designers contributed to all elements of the intervention including the website design, the content, and the level of researcher input during the intervention. Iterative improvements were made based on the unique perspectives and needs of the community experts. During the action planning process, older adults wanted both support and autonomy, while maintaining the freedom to adapt these options to their individual needs. Older adults also preferred a step-by-step approach, allowing for gradual behavior changes across the intervention to avoid feelings of becoming overwhelmed. The co-design process enabled the tailoring of the Small Steps intervention to the specific needs of its intended audience. Key factors contributing to the co-design included flexibility in the design process, fostering a supportive environment, and empowering participants through activities that guided and stimulated their thinking. These elements not only helped shape the development of Small Steps but reinforced the value of co-design in developing personalised interventions for older adults

Mentoring Impact on Leader Efficacy Development: A Field Experiment

While practitioners and scholars tout the importance of mentorship in leader development, few studies have empirically determined whether mentoring actually positively impacts a leader’s development, and if so, in what ways. In a longitudinal field experiment, we examined how a targeted mentorship program that unfolded over 6 months enhanced the development of protégés’ leader efficacy and performance. Results showed that the targeted mentorship intervention increased protégés’ level of leader efficacy more than a comparison intervention that was based on a more eclectic leadership education program delivered in a group setting. Leader efficacy then predicted rated leader performance. Both protégés’ preferences for feedback and trust in the mentor served as important moderators in contributing to the development of leader efficacy. Findings from this longitudinal field experiment could be used by educational institutions and other organizations to enhance their mentorship programs in content, focus, and evaluation of impact

Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations

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Humanity's Last Exam

Benchmarks are important tools for tracking the rapid advancements in large language model (LLM) capabilities. However, benchmarks are not keeping pace in difficulty: LLMs now achieve over 90\% accuracy on popular benchmarks like MMLU, limiting informed measurement of state-of-the-art LLM capabilities. In response, we introduce Humanity's Last Exam (HLE), a multi-modal benchmark at the frontier of human knowledge, designed to be the final closed-ended academic benchmark of its kind with broad subject coverage. HLE consists of 3,000 questions across dozens of subjects, including mathematics, humanities, and the natural sciences. HLE is developed globally by subject-matter experts and consists of multiple-choice and short-answer questions suitable for automated grading. Each question has a known solution that is unambiguous and easily verifiable, but cannot be quickly answered via internet retrieval. State-of-the-art LLMs demonstrate low accuracy and calibration on HLE, highlighting a significant gap between current LLM capabilities and the expert human frontier on closed-ended academic questions. To inform research and policymaking upon a clear understanding of model capabilities, we publicly release HLE at https://lastexam.ai

Report from the Annual Conference of the British Society of Echocardiography, November 2017, Edinburgh International Conference Centre, Edinburgh

No abstract available

Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial

Purpose: Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Methods: The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician’s choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. Results: In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P < 0.01) versus TPC; median OS was 10.0 and 4.8 months, respectively. Improvement in OS was observed in both poorer and better GPA prognostic groups. Survival rates at 12 months were 44.4% for EP versus 19.4% for TPC. Consistent with the overall BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). Conclusions: The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744)