Strong Phase Separation in a Model of Sedimenting Lattices

We study the steady state resulting from instabilities in crystals driven through a dissipative medium, for instance, a colloidal crystal which is steadily sedimenting through a viscous fluid. The problem involves two coupled fields, the density and the tilt; the latter describes the orientation of the mass tensor with respect to the driving field. We map the problem to a 1-d lattice model with two coupled species of spins evolving through conserved dynamics. In the steady state of this model each of the two species shows macroscopic phase separation. This phase separation is robust and survives at all temperatures or noise levels--- hence the term Strong Phase Separation. This sort of phase separation can be understood in terms of barriers to remixing which grow with system size and result in a logarithmically slow approach to the steady state. In a particular symmetric limit, it is shown that the condition of detailed balance holds with a Hamiltonian which has infinite-ranged interactions, even though the initial model has only local dynamics. The long-ranged character of the interactions is responsible for phase separation, and for the fact that it persists at all temperatures. Possible experimental tests of the phenomenon are discussed.Comment: To appear in Phys Rev E (1 January 2000), 16 pages, RevTex, uses epsf, three ps figure

Improving the routine analysis of siderite for δ 13 C and δ 18 O in environmental change research

Rationale The carbon (δ13C) and oxygen (δ18O) isotope composition of siderite (FeCO3) is used widely to understand and quantify geochemical processes in order to reconstruct past climate and environmental change. However, few laboratories follow precisely the same protocol for the preparation and analysis of siderite-bearing materials, which combined with the absence of international reference materials and mineral-specific acid fractionation factors, leads potentially to significant differences in isotope data generated by individual laboratories. Here we examine procedures for the isotope analysis of siderite and discuss factors potentially contributing to inconsistencies in sample measurement data. Methods Isotope analysis of siderite is first assessed using similar versions of the classical off-line, sealed vessel acid digestion method by comparing data sets obtained from intercomparison materials measured at two participating laboratories. We then compare data from the classical method against those generated using an automated preparation technique using data produced from an independent set of test materials. Results Measurement of siderite δ13C is generally both repeatable and reproducible, but measurement of δ18O may be subject to large (~1 ‰), method-dependent bias for siderite reacted at differing temperatures (70 °C and 100 °C) under classical and automated CO2 preparation conditions. The potential for poor oxygen isotope measurement reproducibility is amplified by local differences in sample preparation protocols and procedures used to calibrate measurement data to international reference scales. Conclusions We offer suggestions for improving the repeatability and reproducibility of δ13C and δ18O analysis on siderite. The challenge of producing consistent isotope data from siderite can only be resolved by ensuring the availability of siderite reference materials to facilitate identical treatment as a basis for minimising method-dependent contributions to data inconsistency between laboratories

The genome sequence of the ten-spot ladybird, Adalia decempunctata (Linnaeus, 1758)

We present a genome assembly from an individual male Adalia decempunctata (the ten-spot ladybird; Arthropoda; Insecta; Coleoptera; Coccinellidae). The genome sequence is 489.4 megabases in span. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 19.68 kilobases in length

Impact of metformin use on the cardiovascular effects of dipeptidyl peptidase-4 inhibitors: An analysis of Medicare claims data from 2007 to 2015

Aims: To examine the outcomes of dipeptidyl peptidase-4 (DPP-4) inhibitor initiation with and without concurrent metformin treatment. Materials and methods: We identified Medicare enrollees initiating a DPP-4 inhibitor, a sulphonylurea or a thiazolidinedione. Using propensity-score-weighted Poisson models, we evaluated 1-year cardiovascular (CV) outcome incidence among initiators of DPP-4 inhibitors versus comparators in subgroups with and without concurrent metformin use, and assessed the interaction between initiation drug and metformin. Outcomes included mortality, non-fatal myocardial infarction (MI), stroke, and a composite outcome. Results: For the DPP-4 inhibitor (n = 13 391) versus sulphonylurea (n = 33 206) comparison, rate differences in composite outcome incidence favoured DPP-4 inhibitors: −2.0/100 person-years among metformin users (95% confidence interval [CI] −2.7 to −1.3) and − 1.0/100 person-years (95% CI −1.8 to −0.2) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (−1.5/100 person-years [95% CI −2.1 to −0.9] and −0.7/100 person-years [95% CI −1.4 to 0.0]) and non-fatal MI (−0.5/100 person-years [95% CI −0.8, −0.3] and 0.1/100 person-years [95% CI −0.2 to 0.4]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for non-fatal MI (P = 0.008). For the DPP-4 inhibitor (n = 22 210) versus thiazolidinedione (n = 9517) comparison, rate differences in composite outcome incidence for DPP-4 inhibitor initiation were −0.6/100 person-years (95% CI −1.5 to 0.2) among metformin users and 1.0 (95% CI 0.0 to 2.0) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (−0.5/100 person-years [95% CI −1.3 to 0.1] and 0.8/100 person-years [95% CI −0.0 to 1.7]) and non-fatal MI (−0.1/100 person-years [95% CI −0.4 to 0.2] and 0.2/100 person-years [95% CI −0.1 to 0.6]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for the composite outcome (P = 0.024) and mortality (P = 0.023). Conclusion: Incidence rate differences in multiple CV outcomes appeared more favourable when DPP-4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP-4 inhibitors and metformin

Effect of chemical degradation on fluxes of reactive compounds – a study with a stochastic Lagrangian transport model

In the analyses of VOC fluxes measured above plant canopies, one usually assumes the flux above canopy to equal the exchange at the surface. Thus one assumes the chemical degradation to be much slower than the turbulent transport. We used a stochastic Lagrangian transport model in which the chemical degradation was described as first order decay in order to study the effect of the chemical degradation on above canopy fluxes of chemically reactive species. With the model we explored the sensitivity of the ratio of the above canopy flux to the surface emission on several parameters such as chemical lifetime of the compound, friction velocity, stability, and canopy density. Our results show that friction velocity and chemical lifetime affected the loss during transport the most. The canopy density had a significant effect if the chemically reactive compound was emitted from the forest floor. We used the results of the simulations together with oxidant data measured during HUMPPA-COPEC-2010 campaign at a Scots pine site to estimate the effect of the chemistry on fluxes of three typical biogenic VOCs, isoprene, α-pinene, and β-caryophyllene. Of these, the chemical degradation had a major effect on the fluxes of the most reactive species β-caryophyllene, while the fluxes of α-pinene were affected during nighttime. For these two compounds representing the mono- and sesquiterpenes groups, the effect of chemical degradation had also a significant diurnal cycle with the highest chemical loss at night. The different day and night time loss terms need to be accounted for, when measured fluxes of reactive compounds are used to reveal relations between primary emission and environmental parameters

Metformin use may moderate the effect of DPP-4 inhibitors on cardiovascular outcomes

Objective: To explore prevalent metformin use as a potential moderator of the cardiovascular effects of dipeptidyl peptidase 4 inhibitors (DPP-4i). Research Design and Methods: We performed a meta-analysis of the three major cardiovascular outcomes trials examining DPP-4i. We used meta-regression to examine how the cardiovascular effects of DPP-4i differ between prevalent metformin users and baseline nonusers. Results: While prevalent metformin users experienced a trend toward improved cardiovascular outcomes with DPP-4i (summary hazard ratio [HR] 0.92 [95% CI 0.84, 1.01]), baseline metformin nonusers showed a trend toward harm(HR 1.10 [95% CI 0.97, 1.26]). The difference in overall DPP-4i effect between metformin user and nonuser subgroups was statistically significant (P = 0.036). Conclusions: Baseline metformin status may have a moderating effect on cardiovascular outcomes with DPP-4i use. This hypothesis-generating analysis suggests there is residual uncertainty as to how DPP-4i affect cardiovascular outcomes, depending on concurrently prescribed medications

Dipeptidyl peptidase 4 inhibitors and risk of inflammatory bowel disease among patients with type 2 diabetes: A metaanalysis of randomized controlled trials

A recent retrospective cohort study found that new use of dipeptidyl peptidase 4 inhibitors (DPP4i) of 1.6 years was associated with an increased risk of inflammatory bowel disease (IBD) compared with other antidiabetes medications (hazard ratio 1.75 (95% CI 1.22, 2.49). We previously demonstrated a weak association in an analysis of 86 prevalent and incident cases of IBD among DPP4i users using the U.S. Food and Drug Administration’s Adverse Event Reporting System. In contrast, a cohort study suggested DPP4i initiation reduces risk of autoimmune diseases including IBD. Because the link between DPP4i and IBD remains uncertain, we performed a meta-analysis of randomized controlled trials (RCTs) to evaluate this potential association among patients with type 2 diabetes (T2D)

Sodium-glucose co-transporter-2 inhibitor use and risk of lower-extremity amputation: Evolving questions, evolving answers

Aim: To examine whether sodium-glucose co-transporter-2 (SGLT2) inhibitors are associated with a higher risk of lower-extremity amputation than dipeptidyl-peptidase-4 (DPP-4) inhibitors and sulphonylureas. Methods: We conducted a retrospective cohort study, using the MarketScan Commercial Claims and Encounters Database (2013-2015), to compare the incidence of lower-extremity amputation (LEA) between initiators of SGLT2 inhibitors and initiators of two second-line drugs, DPP-4 inhibitors and sulphonylureas (SUs). We estimated crude incidence rates (IRs) and adjusted hazard ratios (aHR), with 95% confidence intervals (CIs), before and after propensity-score weighting. We additionally conducted sensitivity analyses using a comparator group of all non-metformin, non-SGLT2 inhibitor glucose-lowering drugs, as previous studies used this approach. Results: In a cohort of 328 150 individuals aged 18 to 64 years, the IR of LEA ranged from 1.5 to 2.4 per 1000 person-years. In as-treated analysis, the estimated hazard of LEA was increased among SGLT2 inhibitor initiators compared to DPP-4 inhibitor initiators (aHR 1.69, 95% CI 1.20-2.38), but not compared to SU initiators (aHR 1.02, 95% CI 0.67-1.55) or non-metformin, non-SGLT2 inhibitor initiators (aHR 1.02, 95% CI 0.54-1.93). Results were consistent in intention-to-treat analysis and across a number of sensitivity analyses. Conclusions: Among commercially insured patients in the United States, our results suggest that initiation of SGLT2 inhibitors may increase the risk of LEA compared to initiation of DPP-4 inhibitors. Contrasting results when comparing SGLT2 inhibitor initiators to DPP-4 inhibitor and SU initiators highlight the importance of choosing appropriate comparator drugs when addressing comparative effectiveness and safety questions that can inform clinical decision-making

Effects of liraglutide on cardiovascular outcomes in type 2 diabetes patients with and without baseline metformin use: Post hoc analyses of the LEADER trial

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) reduce cardiovascular (CV) events among patients with type 2 diabetes and high CV risk. Because consensus professional society recommendations endorse metformin as the first-line medication for type 2 diabetes, the CV efficacy of GLP-1RAs has primarily been studied with background metformin therapy. However, the European Society of Cardiology now recommends GLP-1RAs as a first-line type 2 diabetes treatment for patients at high CV risk. These discordant recommendations raise the question of how background metformin might influence the CV benefits of GLP-1RAs. Using data from the LEADER trial,we sought to answer this question by exploring possible heterogeneity in the CV efficacy of liraglutide related to baseline metformin treatment

Newer second-line glucose-lowering drugs versus thiazolidinediones on cirrhosis risk among older US adult patients with type 2 diabetes

Aims: Type 2 diabetes (T2D) accelerates progression of chronic liver disease to cirrhosis, yet the effects of most glucose-lowering drugs (GLDs) on cirrhosis risk in T2D are unknown. To address this gap, we compared cirrhosis risk following initiation of newer second-line GLDs vs. thiazolidinediones (TZDs), which improve histology in non-alcoholic fatty liver disease. Materials and methods: Using the US Medicare Fee-for-Service database (2007–2015) and an active comparator, new-user design, we estimated crude incidence rates (IRs) and propensity-score adjusted hazard ratios (aHR) for incident cirrhosis, comparing newer GLDs (dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i)) vs. TZDs. Results: Among 239,549 total initiators, we observed 318, 151, and < 30 cirrhosis events when comparing DPP4i vs. TZD, GLP1RA vs. TZD, and SGLT2i vs. TZD, respectively. IRs ranged from 1.7 [95% CI, 0.8–3.6] to 3.6 [2.5–5.2] events per 1000 person-years. Point aHR estimates for cirrhosis were elevated among newer GLD initiators vs. TZD (DPP4i: 1.15 [0.89–1.50]; GLP1RA: 1.34 [0.82–2.20]; SGLT2i: 1.16, [0.44–3.08]), although estimates were imprecise due to short durations of drug exposure. Conclusions: We observed mildly elevated cirrhosis risk with newer GLDs vs. TZD; however, uncertainty remains due to imprecise and statistically non-significant effect estimates