Novel diabetes drugs and the cardiovascular specialist

Recently, treatment with 2 newer classes of type 2 diabetes drugs were found to reduce events in patients with diabetes and cardiovascular (CV) disease, a group common in cardiology clinics. The sodium-glucose cotransporter 2 inhibitor, empagliflozin, markedly and rapidly reduced CV death and heart failure hospitalization, likely with hemodynamic/metabolic-driven mechanisms of action. More recently, the glucagon-like peptide–1 receptor agonists liraglutide and semaglutide also reduced CV death and/or major adverse CV events, but did so more slowly and did not influence heart failure risks, suggesting alternative mechanisms of benefit. We will discuss drug therapy for diabetes relative to CV risk, briefly summarize key findings of CV benefit from recent trials, discuss potential mechanisms for benefits of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide–1 agonists, and suggest how such drugs might be embraced by CV specialists to reduce CV events and mortality in their patients

Mapping archaeology while mapping an empire: Using historical maps to reconstruct ancient settlement landscapes in modern India and Pakistan

A range of data sources are now used to support the process of archaeological prospection, including remote sensed imagery, spy satellite photographs and aerial photographs. This paper advocates the value and importance of a hitherto under-utilised historical mapping resource—the Survey of India 1” to 1-mile map series, which was based on surveys started in the mid–late nineteenth century, and published progressively from the early twentieth century AD. These maps present a systematic documentation of the topography of the British dominions in the South Asian Subcontinent. Incidentally, they also documented the locations, the height and area of thousands of elevated mounds that were visible in the landscape at the time that the surveys were carried out, but have typically since been either damaged or destroyed by the expansion of irrigation agriculture and urbanism. Subsequent reanalysis has revealed that many of these mounds were actually the remains of ancient settlements. The digitisation and analysis of these historic maps thus creates a unique opportunity for gaining insight into the landscape archaeology of South Asia. This paper reviews the context within which these historical maps were created, presents a method for georeferencing them, and reviews the symbology that was used to represent elevated mound features that have the potential to be archaeological sites. This paper should be read in conjunction with the paper by Arnau Garcia et al. in the same issue of Geosciences, which implements a research programme combining historical maps and a range of remote sensing approaches to reconstruct historical landscape dynamics in the Indus River Basin.ERC Consolidator Gran

Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation.

Objectives: Ultra-small superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect cellular inflammation within tissues and may help non-invasively identify cardiac transplant rejection. Here, we aimed to determine the normal reference values for USPIO-enhanced MRI in patients with a prior cardiac transplant and examine whether USPIO-enhanced MRI could detect myocardial inflammation in patients with transplant rejection. Methods: Ten volunteers and 11 patients with cardiac transplant underwent T2, T2* and late gadolinium enhancement 1.5T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Results: Ten patients with clinically stable cardiac transplantation were retained for analysis. Myocardial T2 values were higher in patients with cardiac transplant versus healthy volunteers (53.8±5.2 vs 48.6±1.9 ms, respectively; p=0.003). There were no differences in the magnitude of USPIO-induced change in R2* in patients with transplantation (change in R2*, 26.6±7.3 vs 22.0±10.4 s-1 in healthy volunteers; p=0.28). After 3 months, patients with transplantation (n=5) had unaltered T2 values (52.7±2.8 vs 52.12±3.4 ms; p=0.80) and changes in R2* following USPIO (29.42±8.14 vs 25.8±7.8 s-1; p=0.43). Conclusion: Stable patients with cardiac transplantation have increased myocardial T2 values, consistent with resting myocardial oedema or fibrosis. In contrast, USPIO-enhanced MRI is normal and stable over time suggesting the absence of chronic macrophage-driven cellular inflammation. It remains to be determined whether USPIO-enhanced MRI may be able to identify acute cardiac transplant rejection. Trial registration number: NCT02319278349 (https://clinicaltrials.gov/ct2/show/NCT02319278) Registered 03.12.2014 EUDraCT 2013-002336-24

Evolution of active and polar photospheric magnetic fields during the rise of Cycle 24 compared to previous cycles

The evolution of the photospheric magnetic field during the declining phase and minimum of Cycle 23 and the recent rise of Cycle 24 are compared with the behavior during previous cycles. We used longitudinal full-disk magnetograms from the NSO's three magnetographs at Kitt Peak, the Synoptic Optical Long-term Investigations of the Sun (SOLIS) Vector Spectro-Magnetograph (VSM), the Spectromagnetograph and the 512-Channel Magnetograph instruments, and longitudinal full-disk magnetograms from the Mt. Wilson 150-foot tower. We analyzed 37 years of observations from these two observatories that have been observing daily, weather permitting, since 1974, offering an opportunity to study the evolving relationship between the active region and polar fields in some detail over several solar cycles. It is found that the annual averages of a proxy for the active region poloidal magnetic field strength, the magnetic field strength of the high-latitude poleward streams, and the time derivative of the polar field strength are all well correlated in each hemisphere. These results are based on statistically significant cyclical patterns in the active region fields and are consistent with the Babcock-Leighton phenomenological model for the solar activity cycle. There was more hemispheric asymmetry in the activity level, as measured by total and maximum active region flux, during late Cycle 23 (after around 2004), when the southern hemisphere was more active, and Cycle 24 up to the present, when the northern hemisphere has been more active, than at any other time since 1974. The active region net proxy poloidal fields effectively disappeared in both hemispheres around 2004, and the polar fields did not become significantly stronger after this time. We see evidence that the process of Cycle 24 field reversal has begun at both poles.Comment: Accepted for publication in Solar Physic

Metformin and carotid intima media thickness in never smokers with type 1 diabetes: the REMOVAL trial

Aim: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status. Methods: Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. Results: In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (−0.012 mm, 95% CI −0.021 to −0.002; p = .0137) but not in ever-smokers (0.003 mm, 95% CI −0.008 to 0.014; p = .5767); and similarly in non-current smokers (−0.008 mm, 95% CI −0.015 to −0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI −0.007 to 0.032; p = .1887). Three-way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non-current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (−0.020 mm, 95% CI −0.034 to −0.006; p = .0067) but not in ever-smokers (−0.006 mm, 95% CI −0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three-way interaction term. Conclusions: This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce highresolution geospatial estimates of access to drinking water and sanitation facilities. Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest wat

Alpha-particle-induced complex chromosome exchanges transmitted through extra-thymic lymphopoiesis in vitro show evidence of emerging genomic instability

Human exposure to high-linear energy transfer α-particles includes environmental (e.g. radon gas and its decay progeny), medical (e.g. radiopharmaceuticals) and occupational (nuclear industry) sources. The associated health risks of α-particle exposure for lung cancer are well documented however the risk estimates for leukaemia remain uncertain. To further our understanding of α-particle effects in target cells for leukaemogenesis and also to seek general markers of individual exposure to α-particles, this study assessed the transmission of chromosomal damage initially-induced in human haemopoietic stem and progenitor cells after exposure to high-LET α-particles. Cells surviving exposure were differentiated into mature T-cells by extra-thymic T-cell differentiation in vitro. Multiplex fluorescence in situ hybridisation (M-FISH) analysis of naïve T-cell populations showed the occurrence of stable (clonal) complex chromosome aberrations consistent with those that are characteristically induced in spherical cells by the traversal of a single α-particle track. Additionally, complex chromosome exchanges were observed in the progeny of irradiated mature T-cell populations. In addition to this, newly arising de novo chromosome aberrations were detected in cells which possessed clonal markers of α-particle exposure and also in cells which did not show any evidence of previous exposure, suggesting ongoing genomic instability in these populations. Our findings support the usefulness and reliability of employing complex chromosome exchanges as indicators of past or ongoing exposure to high-LET radiation and demonstrate the potential applicability to evaluate health risks associated with α-particle exposure.This work was supported by the Department of Health, UK. Contract RRX95 (RMA NSDTG)