Macroscopic, modular, morphologically simple skeletons occur in the uppermost Mural Formation (Cambrian, Epoch 2, Bonnia–Olenellus Biozone), west-central Alberta and adjacent east-central British Columbia. They represent organisms that lived almost exclusively in reefal environments dominated by archaeocyaths. Some were attached to archaeocyaths or less commonly other surfaces, and some grew downward, apparently from overhangs or cavities in reefs. Qualitative and quantitative data from a large number of specimens, most of which were serially thin sectioned, indicate that they represent a single, remarkably variable species. The skeletal structure ranges among specimens from entirely cerioid to partially to entirely labyrinthine with irregularly incomplete walls. There is also a wide range of variability in growth form among skeletons, in module size and wall thickness among and within skeletons, in module shape within skeletons, and in number and location of projections extending from the wall into some modules. Module increase occurred by peripheral expansion at the basal surface of the skeleton and longitudinal fission involving projections from the wall as module size increased during vertical growth. Walls of skeletons, now composed of calcite cement, were probably originally aragonite. Modular skeletons from the uppermost Mural Formation are assigned to Rosellatana jamesi Kobluk, 1984a, previously represented only by a few cerioid specimens from correlative strata in the Rosella Formation of north-central British Columbia. The skeletal structure and types of module increase in R. jamesi, and a few similar but less well-known Cambrian taxa from elsewhere in North America, suggest a general biologic affinity with hypercalcified sponges.

Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.

In the early morning of February 11, around 4 a.m., a devastating fire swept through the locked cells of a migrant worker detention center in the South Korean city of Yeosu, killing 10 detainees and wounding many others. The center staff tried to put out the flames by spraying fire extinguishers through the bars of the cells, but in an act that can only be described as barbaric, did not unlock the cell doors to free those trapped inside, out of fear that they would escape. Migrant workers behind the locked doors and barred windows were forced to breath in the toxic fumes emitted from burning mattresses. These fumes were the cause of most of the deaths and injuries. The cause of the fire is still under investigation, but the reality is that the roots of the tragedy lie with the Korean government's inhumane policy towards migrant workers.

Objectives/Goals: Large-scale tumor sequencing efforts have led to annotations of novel cancer hotspot mutations that may underlie driver or cooperative function. We have sought to define the molecular consequences of such hotspots associated with pediatric DICER1 syndrome cancers, with the ultimate goal of revealing novel targets that may inform new standards of care. Methods/Study Population: We have performed genomic analysis to identify tumor types (in TCGA and MSK-IMPACT patient data) for which mutations in the Dicer1 gene (encoding Dicer protein) emerge as the dominant signature of driver function. As Dicer is a critical RNA processing factor responsible for the generation of microRNAs, which are posttranscriptional gene regulatory molecules, we have modeled these mutations in human embryonic stem cells in order to study the direct effects on miRNAs and their target genes in an isogenic background. In addition to providing the required setting for unambiguous attribution of function to specific mutations, clonal human ES cells offer an opportunity for modeling of both developmental and cancer requirements associated with altered Dicer function. Results/Anticipated Results: Through generation of genomics and functional datasets from matched genotypes in Dicer mutated human ES cells, we have identified specific alterations in miRNAs and their effects on target genes. Unexpectedly, we found direct evidence for both loss of function and gain of function attributable to Dicer mutations. In addition, through integrated analysis of genomic data from tumor sequencing datasets and our human ES cell models, we have identified potential miRNA and target gene alterations that underlie tumorigenic potential, nominating gene candidates for targeted therapy in DICER1 syndrome. Direct mouse modeling of such candidate gene targets has revealed evidence for driver function of identified miRNA and their targets. Discussion/Significance of Impact: DICER1 syndrome cancers comprise a wide variety of rare pediatric tumor types. Presently, we still lack an effective standard of care. Furthermore, the previous lack of molecular profiling precluded targeted therapy opportunities. Our precise knock-in modeling of Dicer hotspots and deep profiling of relevant tumors now provide candidate targets.

Most people with mental illness in low and middle-income countries (LMICs) do not receive biomedical treatment, though many seek care from traditional healers and faith healers. We conducted a qualitative study in Buyende District, Uganda, using framework analysis. Data collection included interviews with 24 traditional healers, 20 faith healers, and 23 biomedical providers, plus 4 focus group discussions. Interviews explored treatment approaches, provider relationships, and collaboration potential until theoretical saturation was reached. Three main themes emerged: (1) Biomedical providers’ perspectives on traditional and faith healers; (2) Traditional and faith healers’ views on biomedical providers; and (3) Collaboration opportunities and barriers. Biomedical providers viewed faith healers positively but traditional healers as potentially harmful. Traditional and faith healers valued biomedical approaches while feeling variably accepted. Interest in collaboration existed across groups but was complicated by power dynamics, economic concerns, and differing mental illness conceptualizations. Traditional healers and faith healers routinely referred patients to biomedical providers, though reciprocal referrals were rare. The study reveals distinct dynamics among providers in rural Uganda, with historical colonial influences continuing to shape relationships and highlighting the need for integrated, contextually appropriate mental healthcare systems.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

It is shown that the PAR Derivative-Free Nonlinear Regression program in BMDP can be used to fit structural equation models, producing generalized least squares estimates, standard errors, and goodness-of-fit test statistics. Covariance structure models more general than LISREL can be analyzed. The approach is particularly useful for dealing with new non-standard models and experimenting with alternate methods of estimation.

The interface of science and law is a territory frequently occupied by policymakers. In facilitating this interface, epistemic communities have become significant influencers in policymaking, especially at the European Union (EU) level, as a result of its complex multilevel governance system. In this article we assess the quality and nature of interactions between epistemic communities and EU stakeholders on the Horizon-funded project ‘PrecisionTox’, by deploying the concept of epistemic communities developed by Haas, as well as the learning modes of epistemic communities as presented and adapted by Dunlop. The overarching goal of PrecisionTox is to advance the safety assessment of chemicals by establishing a new, cost-effective testing paradigm built from evolutionary theory, which entails reduction, replacement, and refinement of mammalian testing (the 3Rs). The study shows that EU-funded projects can provide an excellent platform for building epistemic communities and forging alliances with EU policymakers, especially when novel technologies may be unlocked and socialized. This study also explores the early interaction of policymakers with epistemic communities through different forms of learning to better understand the complexities surrounding these new technologies in order to set an agenda for policy interventions.

The Prof pegmatite is located NW of Revelstoke, British Columbia, Canada on Boulder Mountain. Due to the abundance of petalite, the pegmatite is classified as a petalite subtype Li-Cs-Ta pegmatite or a Group one pegmatite. The Prof pegmatite contains a suite of minerals indicative of a highly evolved pegmatite melt including petalite, elbaite, lepidolite and Nb–Ta oxides. Four textural zones are present: (1) border; (2) intermediate, including (2.1) graphic texture dominant and (2.2) overgrowth dominant, where diverse minerals form rims around one another; (3) central; and (4) quartz. The border zone has a similar mineralogy to the intermediate zone and is interpreted to represent a chilled margin. The intermediate zone has a feldspar, mica, garnet and dravite–schorl dominant composition. The central zone hosts an evolved pegmatite core, which contains the majority of the lithium mineralisation composed of petalite, elbaite and lepidolite. The tourmaline, Nb–Ta oxides and mica within the pegmatite record the geochemical evolution of the melt from more primitive Fe- and Mg-rich minerals to a Li-, Mn- and Nb-rich assemblage indicative of a highly evolved geochemical system. The various pegmatitic textures and extremely fractionated geochemical composition of the pegmatite indicate that the melt was undercooled and crystallised rapidly. Three phases of metasomatism are recognised in the Prof pegmatite: an albitisation event observed cutting primary orthoclase; followed by a transition to a Na–Li–F-rich event mostly containing secondary albite, trilithionite and elbaites; and a sericitisation event.

The Prof pegmatite has a similar mineralogy to known pegmatites at Mount Begbie, 15 km to the south, in particular the notable presence of the rare mineral qitianlingite, petalite, lepidolite and elbaite. Together, these pegmatite bodies form part of an extensive, poorly mapped pegmatite field. Additional work is required to assess the extent and nature of mineralisation within this field.

The increased severity and frequency of bushfires accompanying human-induced global warming have dire implications for biodiversity conservation. Here we investigate the response of a cryptic, cool-climate elapid, the mustard-bellied snake Drysdalia rhodogaster, to the extensive Black Summer fires of 2019/2020 in south-eastern Australia. The species is categorized as Least Concern on the IUCN Red List (last assessed in 2017), but because a large part of its range was burnt during the Black Summer and little was known about its ecology, D. rhodogaster was identified as a priority species for post-fire impact assessment. We evaluated three lines of evidence to assess the impact of the Black Summer fires on D. rhodogaster. Habitat suitability modelling indicated that c. 46% of the predicted range of the species was affected by bushfire. Field surveys conducted 9–36 months post-fire and collation of records from public databases submitted 0–24 months post-fire indicated that D. rhodogaster persisted in burnt landscapes. Fire severity and proportion of the landscape that was burnt within a 1,000-m radius of survey sites were poor predictors of site occupancy by D. rhodogaster. Although conclusions regarding the effects of fire on D. rhodogaster are limited because of the lack of baseline data, it is evident that the species has persisted across the landscape in the wake of extensive bushfires. Our work highlights the need for baseline knowledge on cryptic species even when they are categorized as Least Concern, as otherwise assessments of the impacts of catastrophic events will be constrained.

This study documents several correlations observed during the first run of the plasma wakefield acceleration experiment E300 conducted at FACET-II, using a single drive electron bunch. The established correlations include those between the measured maximum energy loss of the drive electron beam and the integrated betatron X-ray signal, the calculated total beam energy deposited in the plasma and the integrated X-ray signal, among three visible light emission measuring cameras and between the visible plasma light and X-ray signal. The integrated X-ray signal correlates almost linearly with both the maximum energy loss of the drive beam and the energy deposited into the plasma, demonstrating its usability as a measure of energy transfer from the drive beam to the plasma. Visible plasma light is found to be a useful indicator of the presence of a wake at three locations that overall are two metres apart. Despite the complex dynamics and vastly different time scales, the X-ray radiation from the drive bunch and visible light emission from the plasma may prove to be effective non-invasive diagnostics for monitoring the energy transfer from the beam to the plasma in future high-repetition-rate experiments.