A eukaryote assemblage intercalated with Marinoan glacial deposits in South Australia

Video of digital X-ray tomographs (µCT) in longitudinal plane through cylinder of siltstone, maximum diameter seen (left to right when viewing movie) is 5.4m

Collaborating to support the use and development of open educational resources: a White Rose Libraries research project

Interest in open educational resources (OER) has grown recently due to many external factors, including the restrictive, unsustainable and expensive business models for teaching materials that are being used by some publishers. In February 2021, the libraries of the UK White Rose University Consortium (White Rose Libraries) initiated a research project to explore the potential of OER and to create guidance in the form of an OER toolkit that could be used across all three institutions, and more widely. The project also aimed to seek improvements in the discovery of OER in the Ex Libris Primo discovery service which is used by all three libraries. This article outlines the methodology used to ascertain the needs of the libraries’ user groups to inform the development of the toolkit. A survey of academic staff across all three institutions was conducted, followed by user experience interviews. The survey findings established that more than half of respondents knew little or nothing about OER, and over half also said that they would be likely or extremely likely to consider using or adapting OER, clearly demonstrating the need for more awareness raising and guidance. The survey interview findings were then used to develop and refine the toolkit

Capillary pressure may predict preclinical changes in the eye

This is the final version. Available on open access from Springer Verlag via the DOI in this recordAIMS/HYPOTHESIS: Microvascular dysfunction is associated with end-organ damage. Macular oedema is an important component of diabetic retinopathy. Macular thickness can be accurately quantified by optical coherence tomography (OCT), enabling accurate assessment of the macular prior to clinically apparent abnormalities. We investigated whether macular (fovea) thickness in non-diabetic individuals is related to the microvascular variables controlling fluid filtration across a blood vessel wall, in particular capillary pressure and the microvascular filtration capacity (Kf). METHODS: We recruited 50 non-diabetic individuals (25 men, 25 women; age range: 26-78 years; BMI range: 20-46 kg/m(2)). Fovea thickness was assessed by OCT. Microvascular assessments included: finger nailfold capillary pressure; Kf; microvascular structural assessments, i.e. skin vasodilatory capacity, minimum vascular resistance (MVR) and microvascular distensibility; and endothelial function. RESULTS: At 214.6 (19.9) microm (mean [SD]), fovea thickness was within normal range. Capillary pressure, adjusted for BMI, was associated with fovea thickness (standardised beta 0.573, p = 0.006, linear regression). Fovea thickness was not associated with Kf, microvascular structural assessments or endothelial function. Capillary pressure was still associated with fovea thickness when adjusted for microvascular variables (Kf, vasodilatory capacity, MVR, microvascular distensibility or endothelial function), or for risk factors for diabetes (systemic blood pressure, insulin sensitivity, inflammation, glycaemic status and lipids) and age. CONCLUSIONS/INTERPRETATION: Capillary pressure, a key determinant of movement of fluid across a blood vessel wall, is associated with fovea thickness in non-diabetic individuals. This suggests that with regard to potential preventative or therapeutic targets, attention should be directed at the mechanisms determining retinal microvascular pressure.Diabetes UKNational Institute for Health Research (NIHR

Weight change and sulfonylurea therapy are related to 3 year change in microvascular function in people with type 2 diabetes

Aims/hypothesis: Although cardiovascular disease is the biggest cause of death in people with diabetes, microvascular complications have a significant impact on quality of life and financial burden of the disease. Little is known about the progression of microvascular dysfunction in the early stages of type 2 diabetes before the occurrence of clinically apparent complications. We aimed to explore the determinants of endothelial-dependent and -independent microvascular function progression over a 3 year period, in people with and without both diabetes and few clinical microvascular complications. Methods: Demographics were collected in 154 participants with type 2 diabetes and in a further 99 participants without type 2 diabetes. Skin microvascular endothelium-dependent response to iontophoresis of acetylcholine and endothelium-independent responses to sodium nitroprusside were measured using laser Doppler fluximetry. All assessments were repeated 3 years later. Results: People with type 2 diabetes had impaired endothelial-dependent microvascular response compared with those without (AUC 93.9 [95% CI 88.1, 99.4] vs 111.9 [102.3, 121.4] arbitrary units [AU] × min, p < 0.001, for those with vs without diabetes, respectively). Similarly, endothelial-independent responses were attenuated in those with diabetes (63.2 [59.2, 67.2] vs 75.1 [67.8, 82.4] AU × min, respectively, p = 0.002). Mean microvascular function declined over 3 years in both groups to a similar degree (pinteraction 0.74 for response to acetylcholine and 0.69 for response to sodium nitroprusside). In those with diabetes, use of sulfonylurea was associated with greater decline (p = 0.022 after adjustment for co-prescriptions, change in HbA1c and weight), whereas improving glycaemic control was associated with less decline of endothelial-dependent microvascular function (p = 0.03). Otherwise, the determinants of microvascular decline were similar in those with and without diabetes. The principal determinant of change in microvascular function in the whole population was weight change over 3 years, such that those that lost ≥5% weight had very little decline in either endothelial-dependent or -independent function compared with those that were weight stable, whereas those who gained weight had a greater decline in function (change in endothelial-dependent function was 1.2 [95% CI -13.2, 15.7] AU × min in those who lost weight; -15.8 [-10.5, -21.0] AU × min in those with stable weight; and -37.8 [-19.4, -56.2] AU × min in those with weight gain; ptrend < 0.001). This association of weight change with change in endothelial function was driven by people with diabetes; in people without diabetes, the relationship was nonsignificant. Conclusions/interpretation: Over 3 years, physiological change in weight was the greatest predictor of change in microvascular function.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was supported by the Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006).published version, accepted version (12 month embargo

First Constraints on Compact Dark Matter from Fast Radio Burst Microstructure

Despite existing constraints, it remains possible that up to $35\%$ of all dark matter is comprised of compact objects, such as the black holes in the 10-100\,M$_\odot$ range whose existence has been confirmed by LIGO. The strong gravitational lensing of transients such as FRBs and GRBs has been suggested as a more sensitive probe for compact dark matter than intensity fluctuations observed in microlensing experiments. Recently ASKAP has reported burst substructure down to $15\mu$s timescales in FRBs in the redshift range $0.3-0.5$. We investigate here the implications of this for the detectability of compact dark matter by FRBs. We find that a sample size of $\sim130$ FRBs would be required to constrain compact dark matter to less than the existing 35$\%$ limit with 95$\%$ confidence, if it were distributed along $\gtrsim 1\,$Gpc-long FRB sightlines through the cosmic web. Conversely, existing constraints on the fraction of compact dark matter permit as many as 1 in $\approx 40$ of all $z \lesssim 0.4$ FRBs to exhibit micro-lensed burst structure. Approximately $170$ FRBs intercepting halos within $\sim 50\,$kpc would be required to exclude the fraction of compact dark matter in each intercepted halo to a similar level. Furthermore, we consider the cumulative effects of lensing of the FRB signal by a macroscopic dark matter distribution. We conclude that lensing from a uniform distribution of compact objects is likely not observable, but suggest that FRBs may set meaningful limits on power-law distributions of dark matter.Comment: 3 Figures, 1 tabl

ROBO2 is a stroma suppressor gene in the pancreas and acts via TGF-β signalling.

Whereas genomic aberrations in the SLIT-ROBO pathway are frequent in pancreatic ductal adenocarcinoma (PDAC), their function in the pancreas is unclear. Here we report that in pancreatitis and PDAC mouse models, epithelial Robo2 expression is lost while Robo1 expression becomes most prominent in the stroma. Cell cultures of mice with loss of epithelial Robo2 (Pdx1Cre;Robo2F/F) show increased activation of Robo1+ myofibroblasts and induction of TGF-β and Wnt pathways. During pancreatitis, Pdx1Cre;Robo2F/F mice present enhanced myofibroblast activation, collagen crosslinking, T-cell infiltration and tumorigenic immune markers. The TGF-β inhibitor galunisertib suppresses these effects. In PDAC patients, ROBO2 expression is overall low while ROBO1 is variably expressed in epithelium and high in stroma. ROBO2low;ROBO1high patients present the poorest survival. In conclusion, Robo2 acts non-autonomously as a stroma suppressor gene by restraining myofibroblast activation and T-cell infiltration. ROBO1/2 expression in PDAC patients may guide therapy with TGF-β inhibitors or other stroma /immune modulating agents

Reservoir-Excess Pressure Parameters Independently Predict Cardiovascular Events in Individuals With Type 2 Diabetes

The parameters derived from reservoir-excess pressure analysis (RPA) have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM, and whether they would predict cardiovascular events in individuals with T2DM.We studied 306people with T2DM and cardiovascular disease (CVD)(DMCVD:70.4±7.8yrs), 348people with T2DM but without CVD (DM:67.7±8.4yrs) and 178peoplewithout T2DM or CVD (CTRL:67.2±8.9yrs). RPA-derived parameters including reservoir pressure integral (INTPR), peak reservoir pressure (MAXPR), excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant (DRC) were obtained by radial artery tonometry. INTPR was lower in DMCVD and DM than CTRL. MAXPR was lower, and INTXSP was greater in DMCVD than DM and CTRL. SRC was lower in a stepwise manner among groups(DMCVD&lt;DM&lt;CTRL).DRC was greater in DMCVD than CTRL. In the sub group of individuals with T2DM (n=642), 14 deaths (6 cardiovascular and 9non-cardiovascular causes) and 108cardiovascular events occurred during a 3-yr follow-up period. Logistic regression analysis revealed that INTPR [odds ratio 0.59(95%CI:0.45-0.79)] and DRC [odds ratio 1.60(95%CI:1.25-2.06)] were independent predictors of cardiovascular events during follow-up after adjusting for conventional risk factors(both p&lt;0.001). Further adjustments for potential confounders had no influence on associations. These findings demonstrate that altered RPA-derived parameters are associated with T2DM. Furthermore, baseline values of INTPR and DRC independently predict cardiovascular events in individuals with T2DM, indicating the potential clinical utility of these parameters for risk stratification in T2DM

The unseen host galaxy and high dispersion measure of a precisely-localised Fast Radio Burst suggests a high-redshift origin

FRB 20210912A is a fast radio burst (FRB), detected and localised to sub-arcsecond precision by the Australian Square Kilometre Array Pathfinder. No host galaxy has been identified for this burst despite the high precision of its localisation and deep optical and infrared follow-up, to 5-$\sigma$ limits of $R=26.7$ mag and $K_\mathrm{s}=24.9$ mag with the Very Large Telescope. The combination of precise radio localisation and deep optical imaging has almost always resulted in the secure identification of a host galaxy, and this is the first case in which the line-of-sight is not obscured by the Galactic disk. The dispersion measure of this burst, $\mathrm{DM_{FRB}}=1233.696\pm0.006~\mathrm{pc}\ \mathrm{cm}^{-3}$, allows for a large source redshift of $z>1$ according to the Macquart relation. It could thus be that the host galaxy is consistent with the known population of FRB hosts, but is too distant to detect in our observations ($z>0.7$ for a host like that of the first repeating FRB source, FRB 20121102A); that it is more nearby with a significant excess in $\mathrm{DM_{host}}$, and thus dimmer than any known FRB host; or, least likely, that the FRB is truly hostless. We consider each possibility, making use of the population of known FRB hosts to frame each scenario. The fact of the missing host has ramifications for the FRB field: even with high-precision localisation and deep follow-up, some FRB hosts may be difficult to detect, with more distant hosts being the less likely to be found. This has implications for FRB cosmology, in which high-redshift detections are valuable.Comment: 14 pages, 6 figures. Revised based on referee's comments and accepted to MNRA

The fusion approach – applications for understanding local government and European integration

The article explores the theoretical capabilities of the fusion approach as a conceptual ‘kit’ to explain the ‘bigger picture’ of European integration from a local government perspective. Fusion addresses the rationales and methods facilitating the transfer of policy-making competences to the European level. It understands European integration as a merging of public resources and policy instruments from multiple levels of government, whereby accountability and responsibilities for policy outcomes become blurred. The article argues that the fusion approach is useful to explain the systemic linkages between macro-trajectories and the corresponding change at the local level; the fusion dynamics of the local and European levels in a common policy-cycle; and the attitudes of local actors towards the EU. Although the article concludes that local government is rather modestly ‘fused’ into the EU, fusion approaches allow examining the extent to which the local level has become integrated into the European governance system