Lithofacies and biostratigraphical analysis has enabled the establishment of a stratigraphic event framework for Ludfordian and Pridoli strata in south Wales and the Welsh Borderland. In SW Wales, the Golden Grove Axis acted as a structural hinge separating the shallow marine storm-influenced Cae’r mynach Seaway from a pediment surface above which Ludfordian colluvium (Abercyfor Formation) was deposited. The Axis seeded four NW-derived river-influenced delta progrades of Leintwardinian to early Pridoli age (Tilestones Formation). A NE-sourced early Pridoli wave-influenced delta deposited the Downton Castle Sandstone Formation (DCSF), coeval to the youngest Tilestones prograde, with a lateral interface existing between Mynydd Epynt and the Clun Forest area. Except for the Malverns area, the DCSF is no longer recognized south of the Neath Disturbance. Early Pridoli forced regression promoted widespread subaerial exposure north of the Neath Disturbance, with incision into tracts close to the Welsh Borderland Fault System. The basinward-shift in facies belts resulted in marine erosion and deposition of a phosphatic ravinement pebble lag. The wave-influenced Clifford’s Mesne Sandstone Formation delta subsequently seeded on the Gorsley Axis with tidally influenced Rushall Formation accumulating in a back-barrier setting. The Pwll-Mawr Formation records the easterly advance of coeval coastal deposits on the western side of the remnant Cae’r mynach Seaway. Behind migrating delta coastlines, green muds accumulated on coastal plains (Temeside Mudstone Formation) with better drained red dryland alluvium (Moor Cliffs Formation) charting expansion of Old Red Sandstone lithofacies. Mid-Pridoli incision preserves the Pont ar Llechau Formation estuarine valley fill.

In this work, we present a methodology and a corresponding code-base for constructing mock integral field spectrograph (IFS) observations of simulated galaxies in a consistent and reproducible way. Such methods are necessary to improve the collaboration and comparison of observation and theory results, and accelerate our understanding of how the kinematics of galaxies evolve over time. This code, SimSpin, is an open-source package written in R, but also with an API interface such that the code can be interacted with in any coding language. Documentation and individual examples can be found at the open-source website connected to the online repository. SimSpin is already being utilised by international IFS collaborations, including SAMI and MAGPI, for generating comparable data sets from a diverse suite of cosmological hydrodynamical simulations.

As the scale of cosmological surveys increases, so does the complexity in the analyses. This complexity can often make it difficult to derive the underlying principles, necessitating statistically rigorous testing to ensure the results of an analysis are consistent and reasonable. This is particularly important in multi-probe cosmological analyses like those used in the Dark Energy Survey (DES) and the upcoming Legacy Survey of Space and Time, where accurate uncertainties are vital. In this paper, we present a statistically rigorous method to test the consistency of contours produced in these analyses and apply this method to the Pippin cosmological pipeline used for type Ia supernova cosmology with the DES. We make use of the Neyman construction, a frequentist methodology that leverages extensive simulations to calculate confidence intervals, to perform this consistency check. A true Neyman construction is too computationally expensive for supernova cosmology, so we develop a method for approximating a Neyman construction with far fewer simulations. We find that for a simulated dataset, the 68% contour reported by the Pippin pipeline and the 68% confidence region produced by our approximate Neyman construction differ by less than a percent near the input cosmology; however, they show more significant differences far from the input cosmology, with a maximal difference of 0.05 in $\Omega_{M}$ and 0.07 in w. This divergence is most impactful for analyses of cosmological tensions, but its impact is mitigated when combining supernovae with other cross-cutting cosmological probes, such as the cosmic microwave background.

Background: The Canadian Registry for Amyloidosis Research (CRAR) is a nationwide disease registry of transthyretin (ATTR) and light-chain (AL) amyloidosis. Recent advances in disease-modifying therapy have improved prognosis, however there is a critical need for real-world evidence to address knowledge gaps, particularly longer-term therapeutic outcomes and surveillance strategies. Methods: A multi-stakeholder process was undertaken to develop a consensus dataset for ATTR- and AL-amyloidosis. This process included surveys to rank the importance of potential data items, and a consensus meeting of the CRAR steering committee, (comprised of multidisciplinary clinical experts, and patient organization representatives). Patients and patient organizations supported the development and implementation of a patient-reported dataset. Results: Consensus data items include disease onset, progression, severity, treatments, and outcomes, as well as patient-reported outcomes. Both prospective and retrospective (including deceased) patient cohorts are included. Further baseline data will be presented on an initial cohort of patients. Conclusions: CRAR has been established to collect a longitudinal, multidisciplinary dataset that will evaluate amyloidosis care and outcomes. CRAR has launched at multiple specialty amyloidosis centers nationally and is continually expanding. The growth of this program will promote opportunities to assess real-world safety and efficacy and inform the cost-effectiveness of therapies while supporting patient recruitment for research.

Gaps in the implementation of effective interventions impact nearly all cancer prevention and control strategies in the US including Massachusetts. To close these implementation gaps, evidence-based interventions must be rapidly and equitably implemented in settings serving racially, ethnically, socioeconomically, and geographically diverse populations. This paper provides a brief overview of The Implementation Science Center for Cancer Control Equity (ISCCCE) and describes how we have operationalized our commitment to a robust community-engaged center that aims to close these gaps. We describe how ISCCCE is organized and how the principles of community-engaged research are embedded across the center. Principles of community engagement have been operationalized across all components of ISCCCE. We have intentionally integrated these principles throughout all structures and processes and have developed evaluation strategies to assess whether the quality of our partnerships reflects the principles. ISCCCE is a comprehensive community-engaged infrastructure for studying efficient, pragmatic, and equity-focused implementation and adaptation strategies for cancer prevention in historically and currently disadvantaged communities with built-in methods to evaluate the quality of community engagement. This engaged research center is designed to maximize the impact and relevance of implementation research on cancer control in community health centers.

Genes associated with educational attainment may be related to or interact with adolescent alcohol, tobacco and cannabis use. Potential gene–environment interplay between educational attainment polygenic scores (EA-PGS) and adolescent alcohol, tobacco, and cannabis use was evaluated with a series of regression models fitted to data from a sample of 1871 adult Australian twins. All models controlled for age, age2, cohort, sex and genetic ancestry as fixed effects, and a genetic relatedness matrix was included as a random effect. Although there was no evidence that adolescent alcohol, tobacco or cannabis use interacted with EA-PGS to influence educational attainment, there was a significant, positive gene–environment correlation with adolescent alcohol use at all PGS thresholds (ps <.02). Higher EA-PGS were associated with an increased likelihood of using alcohol as an adolescent (ΔR2 ranged from 0.5% to 1.1%). The positive gene–environment correlation suggests a complex relationship between educational attainment and alcohol use that is due to common genetic factors.

We present Hubble Space Telescope Wide Field Camera 3 photometric and grism observations of the candidate ultra-high-redshift ($z>7$) radio galaxy, GLEAM J0917–0012. This radio source was selected due to the curvature in its 70–230 MHz, low-frequency Murchison Widefield Array radio spectrum and its faintness in K-band. Follow-up spectroscopic observations of this source with the Jansky Very Large Array and Atacama Large Millimetre Array were inconclusive as to its redshift. Our F105W and F0986M imaging observations detect the host of GLEAM J0917–0012 and a companion galaxy, $\sim$ one arcsec away. The G102 grism observations reveal a single weak line in each of the spectra of the host and the companion. To help identify these lines we utilised several photometric redshift techniques including template fitting to the grism spectra, fitting the ultraviolet (UV)-to-radio photometry with galaxy templates plus a synchrotron model, fitting of the UV-to-near-infrared photometry with EAZY, and fitting the radio data alone with RAiSERed. For the host of GLEAM J0917–0012 we find a line at $1.12\,\mu$m and the UV-to-radio spectral energy distribution (SED) fitting favours solutions at $z\sim 2$ or $z\sim 8$. While this fitting shows a weak preference for the lower redshift solution, the models from the higher redshift solution are more consistent with the strength of the spectral line. The redshift constraint by RAiSERed of $>6.5$ also supports the interpretation that this line could be Lyman$-\alpha$ at $z=8.21$; however EAZY favours the $z\sim 2$ solution. We discuss the implications of both solutions. For the companion galaxy we find a line at $0.98\,\mu$m and the SED fitting favours solutions at $z<3$ implying that the line could be the [OII]$\lambda3727$ doublet at $z=1.63$ (although the EAZY solution is $z\sim 2.6\pm 0.5$). Further observations are still required to unambiguously determine the redshift of this intriguing candidate ultra-high-redshift radio galaxy.

Consumption of pork and pork products can be associated with outbreaks of human salmonellosis. Salmonella infection is usually subclinical in pigs, and farm-based control measures are challenging to implement. To obtain data on Salmonella prevalence, samples can be collected from pigs during the slaughter process. Here we report the results of a Great Britain (GB) based abattoir survey conducted by sampling caecal contents from pigs in nine British pig abattoirs during 2019. Samples were collected according to a randomised stratified scheme, and pigs originating from 286 GB farms were included in this survey. Salmonella was isolated from 112 pig caecal samples; a prevalence of 32.2% [95% confidence interval (CI) 27.4–37.4]. Twelve different Salmonella serovars were isolated, with the most common serovars being S. 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium (36.6% of Salmonella-positive samples), followed by S. Derby (25.9% of Salmonella-positive samples). There was no significant difference compared to the estimate of overall prevalence (30.5% (95% CI 26.5–34.6)) obtained in the last abattoir survey conducted in the UK (2013). Abattoir-based control measures are often effective in the reduction of Salmonella contamination of carcasses entering the food chain. In this study, the effect of abattoir hygiene practices on the prevalence of Salmonella on carcasses was not assessed. Continuing Salmonella surveillance at slaughter is recommended to assess effect of farm-based and abattoir-based interventions and to monitor potential public health risk associated with consumption of Salmonella-contaminated pork products.

We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive ( ${>}7 \times 10^{10} {\mathrm{M}}_\odot$ ) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ( $0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$ , as well as hundreds of emission-line sources at $z < 6$ . This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$ . MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.

We present an analytical study of two-dimensional flow in a wedge driven by a time-dependent surface heat flux as a model problem to understand buoyancy-induced cross-shore flow. Besides the turbulent Prandtl number and the relevant Rayleigh number, both assumed to be of order unity, the solution is seen to depend on the geometry through a parameter $\beta$, representing the bottom slope. An analytic solution is sought in the asymptotic limit $\beta \ll 1$ for a water layer bounded by an adiabatic bottom surface subject to a harmonic heat flux on the upper surface. The analysis reveals that the motion at leading order can be expressed as the sum of a harmonic component and a steady component, the latter driven by nonlinear advection. This steady-streaming motion includes a near-shore vortex with associated recirculating motion that can affect cross-shore transport and dispersion in coastal environments. The analytical solution is compared with numerical solutions of the complete conservation equations for small values of $\beta$. Excellent quantitative agreement is found for values of the Rayleigh number below a critical value at which the periodic solution undergoes a period-doubling bifurcation, leading to the establishment of thermal-instability cells that dominate the offshore flow dynamics, while the near-shore dynamics remains well described by the analytical solution. The analysis illustrates that a periodic heat input that leads to a vertically inhomogeneous temperature distribution can result in residual motion, net heat fluxes and persistent temperature structure in the cross-shore direction.

Maternal nutrition is critical in mammalian development, influencing the epigenetic reprogramming of gametes, embryos, and fetal programming. We evaluated the effects of different levels of sulfur (S) and cobalt (Co) in the maternal diet throughout the pre- and periconceptional periods on the biochemical and reproductive parameters of the donors and the DNA methylome of the progeny in Bos indicus cattle. The low-S/Co group differed from the control with respect to homocysteine, folic acid, B12, insulin growth factor 1, and glucose. The oocyte yield was lower in heifers from the low S/Co group than that in the control heifers. Embryos from the low-S/Co group exhibited 2320 differentially methylated regions (DMRs) across the genome compared with the control embryos. We also characterized candidate DMRs linked to the DNMT1 and DNMT3B genes in the blood and sperm cells of the adult progeny. A DMR located in DNMT1 that was identified in embryos remained differentially methylated in the sperm of the progeny from the low-S/Co group. Therefore, we associated changes in specific compounds in the maternal diet with DNA methylation modifications in the progeny. Our results help to elucidate the impact of maternal nutrition on epigenetic reprogramming in livestock, opening new avenues of research to study the effect of disturbed epigenetic patterns in early life on health and fertility in adulthood. Considering that cattle are physiologically similar to humans with respect to gestational length, our study may serve as a model for studies related to the developmental origin of health and disease in humans.

Life course research embraces the complexity of health and disease development, tackling the extensive interactions between genetics and environment. This interdisciplinary blueprint, or theoretical framework, offers a structure for research ideas and specifies relationships between related factors. Traditionally, methodological approaches attempt to reduce the complexity of these dynamic interactions and decompose health into component parts, ignoring the complex reciprocal interaction of factors that shape health over time. New methods that match the epistemological foundation of the life course framework are needed to fully explore adaptive, multilevel, and reciprocal interactions between individuals and their environment. The focus of this article is to (1) delineate the differences between lifespan and life course research, (2) articulate the importance of complex systems science as a methodological framework in the life course research toolbox to guide our research questions, (3) raise key questions that can be asked within the clinical and translational science domain utilizing this framework, and (4) provide recommendations for life course research implementation, charting the way forward. Recent advances in computational analytics, computer science, and data collection could be used to approximate, measure, and analyze the intertwining and dynamic nature of genetic and environmental factors involved in health development.

Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.

A sphere sinking through a chemical gradient drags fluid with it, deforming the gradient. The sphere leaves a trail of gradient enhancement that persists longer than the velocity disturbance in the Reynolds $10^{-2}\leqslant Re\leqslant 10^{2}$, Froude $10^{-1}\leqslant Fr\leqslant 10^{3}$ and Péclet $10^{2}<Pe\leqslant 10^{6}$ regime considered here. We quantify the enhancement of the gradient and the diffusive flux in the trail of disturbed chemical left by the passing sphere using a combination of numerical simulations and scaling analyses. When $Fr$ is large and buoyancy forces are negligible, dragged isosurfaces of chemical form a boundary layer of thickness $\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}$ around the sphere with diameter $l$. We derive the scaling $\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}/l\sim \mathit{Pe}^{-1/3}$ from the balance of advection and diffusion in the chemical boundary layer. The sphere displaces a single isosurface of chemical a maximum distance $\mathit{L}_{Def}$ that increases as $\mathit{L}_{Def}/l\sim l/\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}\sim \mathit{Pe}^{1/3}$. Increased flux through the chemical boundary layer moving with the sphere is described by a Sherwood number, $Sh\sim l/\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}\sim \mathit{Pe}^{1/3}$. The gradient enhancement trail extends much farther than $\mathit{L}_{Def}$ as displaced isosurfaces slowly return to their original positions through diffusion. In the reference frame of a chemical isosurface moving past the sphere, a new quantity describing the Lagrangian flux is found to scale as $\mathit{M}\sim (\mathit{L}_{Def}/l)^{2}\sim \mathit{Pe}^{2/3}$. The greater $\mathit{Pe}$ dependence of $\mathit{M}$ versus $Sh$ demonstrates the importance of the deformation trail for determining the total flux of chemical in the system. For $\mathit{Fr}\geqslant 10$, buoyancy forces are weak compared to the motion of the sphere and the preceding results are retained. Below $\mathit{Fr}=10$, an additional Froude dependence is found and $l/\unicode[STIX]{x1D6FF}_{\unicode[STIX]{x1D70C}}\sim Sh\sim Re^{1/6}Fr^{-1/6}Pe^{1/3}$. Buoyancy forces suppress gradient deformation downstream, resulting in $\mathit{L}_{Def}/l\sim Re^{-1/3}Fr^{1/3}Pe^{1/3}$ and $\mathit{M}\sim Re^{-1/3}Fr^{1/3}Pe^{2/3}$. The productivity of marine plankton – and therefore global carbon and oxygen cycles – depends on the availability of microscale gradients of chemicals. Because most plankton exist in the fluids regime under consideration, this work describes a new mechanism by which sinking particles and plankton can stir weak ambient chemical gradients a distance $\mathit{L}_{Def}$ and increase chemical flux in the trail by a factor of $\mathit{M}$.