Network meta-analysis allows the synthesis of relative effects from several treatments. Two broad approaches are available to synthesize the data: arm-synthesis and contrast-synthesis, with several models that can be fitted within each. Limited evaluations comparing these approaches are available. We re-analyzed 118 networks of interventions with binary outcomes using three contrast-synthesis models (CSM; one fitted in a frequentist framework and two in a Bayesian framework) and two arm-synthesis models (ASM; both fitted in a Bayesian framework). We compared the estimated log odds ratios, their standard errors, ranking measures and the between-trial heterogeneity using the different models and investigated if differences in the results were modified by network characteristics. In general, we observed good agreement with respect to the odds ratios, their standard errors and the ranking metrics between the two Bayesian CSMs. However, differences were observed when comparing the frequentist CSM and the ASMs to each other and to the Bayesian CSMs. The network characteristics that we investigated, which represented the connectedness of the networks and rareness of events, were associated with the differences observed between models, but no single factor was associated with the differences across all of the metrics. In conclusion, we found that different models used to synthesize evidence in a network meta-analysis (NMA) can yield different estimates of odds ratios and standard errors that can impact the final ranking of the treatment options compared.

How should we respond to extremist views that we know are false? This paper proposes that we should be intellectually humble, but not open-minded. We should own our intellectual limitations, but be unwilling to revise our beliefs in the falsity of the extremist views. The opening section makes a case for distinguishing the concept of intellectual humility from the concept of open-mindedness, arguing that open-mindedness requires both a willingness to revise extant beliefs and other-oriented engagement, whereas intellectual humility requires neither. Building on virtue-consequentialism, the second section makes a start by arguing that intellectually virtuous people of a particular sort—people with “effects-virtues”—would be intellectually humble, but not open-minded, in responding to extremist views they knew were false. We suggest that while intellectual humility and open-mindedness often travel together, this is a place where they come apart.

OBJECTIVES/GOALS: The COVID-19 pandemic disrupted HIV care, though it prompted preventive measures for respiratory pathogens, particularly among PWH. We therefore quantified trends in respiratory ADE incidence during vs. before the COVID-19 pandemic to assess effects of these measures on non-COVID-19 illnesses. METHODS/STUDY POPULATION: We included PWH aged ≥18 years in care at the Vanderbilt Comprehensive Care Clinic in Nashville, Tennessee from 2017-2023. Individuals contributed time from the last of March 31, 2017 or clinic enrollment until the first of death, March 31, 2023 (study close), or final clinic visit (if there was no visit ≤12 months before study close). We described respiratory ADE incidences (per 1,000 person-years) in each year of the study; we used Poisson regression with robust variance to estimate the incidence rate ratio (IRR) and 95% confidence interval (CI) for respiratory ADEs in the three years following vs. before the World Health Organization’s pandemic designation for COVID-19 (March 2020). RESULTS/ANTICIPATED RESULTS: Among 4,880 persons contributing 19,510 person-years, 69 (1.4%) developed ≥1 respiratory ADE. Median age at cohort entry was 42.6 (interquartile range [IQR]: 32.1, 52.3) years and at first respiratory ADE was 43.6 (IQR: 36.1, 51.2) years. The overall average respiratory ADE incidence in the pre-pandemic period (March 2017-March 2020) was 4.5 (95% CI: 3.3-6.3) per 1,000 person-years and during the post-pandemic period (April 2020-March 2023) was 4.1 (95% CI: 1.8-9.0) per 1,000 person-years. When accounting for repeated outcomes and annual variation, the modeled respiratory ADE incidence was 10% lower (IRR=0.9, 95% CI: 0.6-1.4) during vs. before the COVID-19 pandemic. DISCUSSION/SIGNIFICANCE: Respiratory ADE incidence dropped 10% following the COVID-19 pandemic declaration, though the confidence interval for this change contains the null. It is plausible that nonpharmaceutical COVID-19 mitigation measures drove a brief but impermanent decline, though further research is needed to assess whether diagnostic biases also played a role.

We investigate a variety of cut and choose games, their relationship with (generic) large cardinals, and show that they can be used to characterize a number of properties of ideals and of partial orders: certain notions of distributivity, strategic closure, and precipitousness.

The Altar Stone at Stonehenge in Wiltshire, UK, is enigmatic in that it differs markedly from the other bluestones. It is a grey–green, micaceous sandstone and has been considered to be derived from the Old Red Sandstone sequences of South Wales. Previous studies, however, have been based on presumed derived fragments (debitage) that have been identified visually as coming from the Altar Stone. Portable X-ray fluorescence (pXRF) analyses were conducted on these fragments (ex situ) as well as on the Altar Stone (in situ). Light elements (Z<37) in the Altar Stone analyses, performed after a night of heavy rain, were affected by surface and pore water that attenuate low energy X-rays, however the dry analyses of debitage fragments produced data for a full suite of elements. High Z elements, including Zr, Nb, Sr, Pb, Th and U, all occupy the same compositional space in the Altar Stone and debitage fragments, and are statistically indistinguishable, indicating the fragments are derived from the Altar Stone. Barium compares very closely between the debitage and Altar Stone, with differences being related to variable baryte distribution in the Altar Stone, limited accessibility of its surface for analysis, and probably to surface weathering.

A notable feature of the Altar Stone sandstone is the presence of baryte (up to 0.8 modal%), manifest as relatively high Ba in both the debitage and the Altar Stone. These high Ba contents are in marked contrast with those in a small set of Old Red Sandstone field samples, analysed alongside the Altar Stone and debitage fragments, raising the possibility that the Altar Stone may not have been sourced from the Old Red Sandstone sequences of Wales. This high Ba ‘fingerprint’, related to the presence of baryte, may provide a rapid test using pXRF in the search for the source of the Stonehenge Altar Stone.

The coronavirus disease (COVID-19) pandemic has had profound consequences on collective mental health and well-being, and yet, older adults appear better off than younger adults. The current study examined mental health impacts of the pandemic across adult age groups in a large sample (n = 5,320) of Canadians using multiple hierarchical regression analyses. Results suggest older adults are experiencing better mental health and more social connectedness relative to younger adults. Loneliness predicted negative mental health outcomes across all age groups, while the negative association between social support and mental health was only significant at average and high levels of loneliness in the 65–69 age group. Results point towards differential mental health impacts of the pandemic across adult age groups and indicate that loneliness and social support may be key intervention targets during the COVID-19 pandemic. Future research should further examine mechanisms of resiliency among older Canadian adults during the pandemic.

Accurately dating the creation and development of earthwork features is a long-standing problem for archaeologists. This article presents results from Bosigran (Cornwall, UK), where boundary banks believed to be prehistoric in origin are assessed using optically stimulated luminescence profiling and dating (OSL-PD). The results provide secure construction dates for different boundaries in the Bronze and Iron Ages, as well as chronologies for their early medieval and later development. The research demonstrates not only the prehistoric origins of these distinctive Cornish field systems, but also a practical and cost-effective methodology suitable for dating earthworks around the world.

OBJECTIVES/SPECIFIC AIMS: Previous research suggests that weight loss during early TB treatment (first two months of anti-TB therapy) is a predictor of poor tuberculosis (TB) treatment outcomes among HIV-negative populations, but the relationship has not been well studied in the context of HIV. We examined the association between HIV and weight change during the first two months of anti-tuberculosis treatment, and also assessed the effects of HIV and early weight change on tuberculosis (TB) treatment outcomes. METHODS/STUDY POPULATION: Adults with culture-confirmed, drug-susceptible, pulmonary TB, regardless of HIV status, were enrolled into the Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil cohort and followed on standard anti-TB therapy. For the primary analysis, we compared weight change in persons living with HIV (PLWH) and HIV-negative patients between baseline and two months using multivariable bootstrapped quantile regression and modified Poisson regression. For secondary analysis, we examined the separate effects of HIV and weight change on poor TB treatment outcome (treatment failure, TB recurrence, or death) using Cox proportional hazards regression. RESULTS/ANTICIPATED RESULTS: Among 323 participants, 45 (14%) were HIV-positive. On average, PLWH lost 0.7% (interquartile range (IQR): −5.1%, 4.4%) of their baseline body weight between baseline and two months; those without HIV gained 3.5% (IQR: 0.8%, 6.7%). After adjusting for age, sex, and baseline BMI, PLWH lost 4.1% (95% confidence interval (CI): −6.5%, −1.6%) more weight during the first two months of anti-TB treatment than HIV-negative individuals. HIV infection was associated with weight loss ≥5% (adjusted odds ratio = 9.3; 95% CI: 4.2-20.6). Regarding the secondary analysis, 14 patients had a poor TB treatment outcome: 2 treatment failures, 4 cases of recurrent TB, and 8 deaths. PLWH and patients who lost ≥5% weight had significantly increased risk of poor TB treatment outcome with hazard ratios of 8.77 (95% CI: 2.96-25.94) and 4.09 (95% CI: 1.11-15.14), respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that HIV is associated with weight loss during early TB treatment, and both HIV and early weight loss were associated with poor treatment outcome. Future research should examine the potential etiologies of these findings and identify the types of interventions that would best promote weight gain during TB treatment, especially among PLWH, in order to prevent poor TB treatment outcomes.

Syphacia stroma (von Linstow, 1884) Morgan, 1932 and Syphacia frederici Roman, 1945 are oxyurid nematodes that parasitize two murid rodents, Apodemus sylvaticus and Apodemus flavicollis, on the European mainland. Only S. stroma has been recorded previously in Apodemus spp. from the British Isles. Despite the paucity of earlier reports, we identified S. frederici in four disparate British sites, two in Nottinghamshire, one each in Berkshire and Anglesey, Wales. Identification was based on their site in the host (caecum and not small intestine), on key morphological criteria that differentiate this species from S. stroma (in particular the tail of female worms) and by sequencing two genetic loci (cytochrome C oxidase 1 gene and a section of ribosomal DNA). Sequences derived from both genetic loci of putative British S. frederici isolates formed a tight clade with sequences from continental worms known to be S. frederici, clearly distinguishing these isolates from S. stroma which formed a tight clade of its own, distinct from clades representative of Syphacia obvelata from Mus and S. muris from Rattus. The data in this paper therefore constitute the first record of S. frederici from British wood mice, and confirm the status of this species as distinct from both S. obvelata and S. stroma.

U60 ([UO2(O2)(OH)]60 60− in water) is a uranyl peroxide nanocluster with a fullerene topology and O h symmetry. U60 clusters can exist in crystalline solids or in liquids; however, little is known of their behavior at high pressures. We compressed the U60-bearing material: Li68K12(OH)20[UO2(O2)(OH)]60(H2O)310 ( $Fm\bar 3$ ; a = 37.884 Å) in a diamond anvil cell to determine its response to increasing pressure. Three length scales and corresponding structural features contribute to the compression response: uranyl peroxide bonds (<0.5 nm), isolated single nanoclusters (2.5 nm), and the long-range periodicity of nanoclusters within the solid (>3.7 nm). Li68K12(OH)20[UO2(O2)(OH)]60(H2O)310 transformed to a tetragonal structure below 2 GPa and irreversibly amorphized between 9.6 and 13 GPa. The bulk modulus of the tetragonal U60-bearing material was 25 ± 2 GPa. The pressure-induced amorphous phase contained intact U60 clusters, which were preserved beyond the loss of long-range periodicity. The persistence of U60 clusters at high pressure may have been enhanced by the interaction between U60 nanoclusters and the alcohol pressure medium. Once formed, U60 nanoclusters persist regardless of their associated long-range ordering—in crystals, amorphous solids, or solutions.

Puccinia obtegens (Link) Tul., an autoecious rust pathogen, is a potential biological control agent of Canada thistle [Cirsium arvense (L.) Scop.]. Ten ecotypes of Canada thistle were inoculated with uredospores of P. obtegens and sporulation was observed on all ecotypes. Infection types varied among and within ecotypes, indicating that host-resistance is one factor limiting rust infection. No correlation was found between Canada thistle susceptibility to the rust and host plant ecotype classification, stomatal density, amount of leaf pubescence, or spore germinability on leaf surfaces.