First recorded occurrence of detrital baddeleyite (ZrO2) in sedimentary rock (Smith Bank Formation, Triassic, Central North Sea)

Acknowledgements and Funding The authors wish to thank John Still of the University of Aberdeen for his invaluable assistance with the SEM-EDS analyses. This work was conducted as part of the Triassic Mudstones Joint Industry Project which was sponsored by BP, ConocoPhillips, EON E&P, Esso Exploration and Production UK Limited, GDF SUEZ E&P UK Ltd, JX Nippon, Maersk Oil, Shell and Total.Peer reviewedPostprin

Geometric Generalisations of SHAKE and RATTLE

A geometric analysis of the Shake and Rattle methods for constrained Hamiltonian problems is carried out. The study reveals the underlying differential geometric foundation of the two methods, and the exact relation between them. In addition, the geometric insight naturally generalises Shake and Rattle to allow for a strictly larger class of constrained Hamiltonian systems than in the classical setting. In order for Shake and Rattle to be well defined, two basic assumptions are needed. First, a nondegeneracy assumption, which is a condition on the Hamiltonian, i.e., on the dynamics of the system. Second, a coisotropy assumption, which is a condition on the geometry of the constrained phase space. Non-trivial examples of systems fulfilling, and failing to fulfill, these assumptions are given

Evolutionary action and structural basis of the allosteric switch controlling β(2)AR functional selectivity

Functional selectivity of G-protein-coupled receptors is believed to originate from ligand-specific conformations that activate only subsets of signaling effectors. In this study, to identify molecular motifs playing important roles in transducing ligand binding into distinct signaling responses, we combined in silico evolutionary lineage analysis and structure-guided site-directed mutagenesis with large-scale functional signaling characterization and non-negative matrix factorization clustering of signaling profiles. Clustering based on the signaling profiles of 28 variants of the β(2)-adrenergic receptor reveals three clearly distinct phenotypical clusters, showing selective impairments of either the Gi or βarrestin/endocytosis pathways with no effect on Gs activation. Robustness of the results is confirmed using simulation-based error propagation. The structural changes resulting from functionally biasing mutations centered around the DRY, NPxxY, and PIF motifs, selectively linking these micro-switches to unique signaling profiles. Our data identify different receptor regions that are important for the stabilization of distinct conformations underlying functional selectivity

Multi-k⃗\vec{k} Configurations

Using resonant x-ray scattering to perform diffraction experiments at the U M$_{4}$ edge novel reflections of the generic form have been observed in UAs$_{0.8}$Se$_{0.2}$ where $\vec{k} = $, with $k = {1/2}$ reciprocal lattice units, is the wave vector of the primary (magnetic) order parameter. The reflections, with $10^{-4}$ of the magnetic intensities, cannot be explained on the basis of the primary order parameter within standard scattering theory. A full experimental characterisation of these reflections is presented including their energy, azimuthal and temperature dependencies. On this basis we establish that the reflections most likely arise from the electric dipole operator involving transitions between the core 3d and partially filled $5f$ states. The temperature dependence couples the peak to the triple-$\vec{k}$ region of the phase diagram: Below $\sim 50$ K, where previous studies have suggested a transition to a double-$\vec{k}$ state, the intensity of the $$ is dramatically reduced. Whilst we are unable to give a definite explanation of how these novel reflections appear, this paper concludes with a discussion of possible ideas for these reflections in terms of the coherent superposition of the 3 primary (magnetic) order parameters

Crossing borders: new teachers co-constructing professional identity in performative times

This paper draws on a range of theoretical perspectives on the construction of new teachers’ professional identity. It focuses particularly on the impact of the development in many national education systems of a performative culture of the management and regulation of teachers’ work. Whilst the role of interactions with professional colleagues and school managers in the performative school has been extensively researched, less attention has been paid to new teachers’ interactions with students. This paper highlights the need for further research focusing on the process of identity co-construction with students. A key theoretical concept employed is that of liminality, the space within which identities are in transition as teachers adjust to the culture of a new professional workplace, and the nature of the engagement of new teachers, or teachers who change schools, with students. The authors argue that an investigation into the processes of this co-construction of identity offers scope for new insights into the extent to which teachers might construct either a teacher identity at odds with their personal and professional values, or a more ‘authentic’ identity that counters performative discourses. These insights will in turn add to our understanding of the complex range of factors impacting on teacher resilience and motivation

Survey of UK histopathology consultants’ attitudes towards academic and molecular pathology

Objective: Academic pathology is facing a crisis; an ongoing decline in academic pathology posts, a paucity of academic pathologist’s in-training and unfilled posts at a time when cellular pathology departments are challenged to deliver increasing numbers of molecular tests. The National Cancer Research Institute initiative in Cellular & Molecular Pathology commissioned a survey to assess attitudes of cellular pathology consultants towards research in order to understand barriers and identify possible solutions to improve this situation. As cellular pathology is encompassing an increasing number of diagnostic molecular tests, we also surveyed the current approach to and extent of training in molecular pathology. Methods: The survey was distributed to all UK-based consultant pathologists via the Pathological Society of Great Britain & Ireland and Royal College of Pathologist networks. Heads of Department were contacted separately to obtain figures for number of academic training and consultant posts. Results: 302 cellular pathologists completed the survey which represents approximately 21% of the total cellular histopathology workforce. Most respondents (89%) had been involved in research at some point; currently, 22% were undertaking research formally, and 41% on an informal basis. Of those previously involved in research, 57% stopped early in their consultant career. The majority of substantive academic posts were Professors of which 60% had been in post for >20 years. Most respondents (84%) used molecular pathology in diagnostic work, independent of where they worked or the length of time in post. Notably, 53% of consultants had not received molecular pathology training, particularly more senior consultants and consultants in district general hospitals. Conclusions: The survey reveals that the academic workforce is skewed towards senior individuals, many of whom are approaching retirement, with a missing cohort of ‘junior consultant’ academic pathologists to replace them. Most pathologists stop formal research activity at the beginning of a consultant career. While molecular pathology is an increasing part of a pathologist’s workload, the majority of consultant cellular pathologists have not received any formal molecular training

Data quality considerations for evaluating COVID-19 treatments using real world data: learnings from the National COVID Cohort Collaborative (N3C)

Background: Multi-institution electronic health records (EHR) are a rich source of real world data (RWD) for generating real world evidence (RWE) regarding the utilization, benefits and harms of medical interventions. They provide access to clinical data from large pooled patient populations in addition to laboratory measurements unavailable in insurance claims-based data. However, secondary use of these data for research requires specialized knowledge and careful evaluation of data quality and completeness. We discuss data quality assessments undertaken during the conduct of prep-to-research, focusing on the investigation of treatment safety and effectiveness. Methods: Using the National COVID Cohort Collaborative (N3C) enclave, we defined a patient population using criteria typical in non-interventional inpatient drug effectiveness studies. We present the challenges encountered when constructing this dataset, beginning with an examination of data quality across data partners. We then discuss the methods and best practices used to operationalize several important study elements: exposure to treatment, baseline health comorbidities, and key outcomes of interest. Results: We share our experiences and lessons learned when working with heterogeneous EHR data from over 65 healthcare institutions and 4 common data models. We discuss six key areas of data variability and quality. (1) The specific EHR data elements captured from a site can vary depending on source data model and practice. (2) Data missingness remains a significant issue. (3) Drug exposures can be recorded at different levels and may not contain route of administration or dosage information. (4) Reconstruction of continuous drug exposure intervals may not always be possible. (5) EHR discontinuity is a major concern for capturing history of prior treatment and comorbidities. Lastly, (6) access to EHR data alone limits the potential outcomes which can be used in studies. Conclusions: The creation of large scale centralized multi-site EHR databases such as N3C enables a wide range of research aimed at better understanding treatments and health impacts of many conditions including COVID-19. As with all observational research, it is important that research teams engage with appropriate domain experts to understand the data in order to define research questions that are both clinically important and feasible to address using these real world data

Manganites at Quarter Filling: Role of Jahn-Teller Interactions

We have analyzed different correlation functions in a realistic spin-orbital model for half-doped manganites. Using a finite-temperature diagonalization technique the CE phase was found in the charge-ordered phase in the case of small antiferromagnetic interactions between $t_{2g}$ electrons. It is shown that a key ingredient responsible for stabilization of the CE-type spin and orbital-ordered state is the cooperative Jahn-Teller (JT) interaction between next-nearest Mn$^{+3}$ neighbors mediated by the breathing mode distortion of Mn$^{+4}$ octahedra and displacements of Mn$^{+4}$ ions. The topological phase factor in the Mn-Mn hopping leading to gap formation in one-dimensional models for the CE phase as well as the nearest neighbor JT coupling are not able to produce the zigzag chains typical for the CE phase in our model.Comment: 16 pages with 16 figures, contains a more detailed parameter estimate based on the structural data by Radaelli et al. (accepted for publication in Phys. Rev. B