Three-Dimensional Spontaneous Flow Transition in a Homeotropic Active Nematic

We study the three-dimensional spontaneous flow transition of an active nematic in an infinite slab geometry using a combination of numerics and analytics. We show that it is determined by the interplay of two eigenmodes -- called S- and D-mode -- that are unstable at the same activity threshold and spontaneously breaks both rotational symmetry and chiral symmetry. The onset of the unstable modes is described by a non-Hermitian integro-differential operator, which we determine their exponential growth rates from using perturbation theory. The S-mode is the fastest growing. After it reaches a finite amplitude, the growth of the D-mode is anisotropic, being promoted perpendicular to the S-mode and suppressed parallel to it, forming a steady state with a full three-dimensional director field and a well-defined chirality. Lastly, we derive a model of the leading-order time evolution of the system close to the activity threshold.Comment: 16 pages, 7 figure

Three-dimensional spontaneous flow transition in a homeotropic active nematic

Active nematics are driven, non-equilibrium systems relevant to biological processes including tissue mechanics and morphogenesis, and to active metamaterials in general. We study the three-dimensional spontaneous flow transition of an active nematic in an infinite slab geometry using a combination of numerics and analytics. We show that it is determined by the interplay of two eigenmodes – called S- and D-mode – that are unstable at the same activity threshold and spontaneously breaks both rotational symmetry and chiral symmetry. The onset of the unstable modes is described by a non-Hermitian integro-differential operator, which we determine their exponential growth rates from using perturbation theory. The S-mode is the fastest growing. After it reaches a finite amplitude, the growth of the D-mode is anisotropic, being promoted perpendicular to the S-mode and suppressed parallel to it, forming a steady state with a full three-dimensional director field and a well-defined chirality. Lastly, we derive a model of the leading-order time evolution of the system close to the activity threshold

Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development

WSTĘP. Chociaż wyniki prospektywnych prac wskazują, że zaburzenia działania i wydzielania insuliny zapowiadają wystąpienie cukrzycy typu 2, jednakże nie dostarczają one dostatecznych informacji o współudziale tych dwóch czynników w pogarszaniu tolerancji glukozy w różnych okresach rozwoju cukrzycy typu 2. Dlatego autorzy podjęli próbę niezależnej oceny wpływu zaburzeń wydzielania i działania insuliny na przejście od stanu prawidłowej tolerancji glukozy (NGT, normal glucose tolerance) do tolerancji nieprawidłowej (IGT, impaired glucose tolerance) i ze stanu IGT w cukrzycę. MATERIAŁ I METODY. U 254 Indian Pima z NGT i u 145 z IGT autorzy badali stymulowane insuliną usuwanie glukozy (M) (klamra hiperinsulinowa), wielkość wydzielania insuliny w fazie wczesnej (AIR, acute insulin secretory response) (25-gramowy dożylny test tolerancji glukozy) i zawartość składników ciała (hydrodensytometria lub ilościowa radiografia cyfrowa). Czas obserwacji tych osób wynosił 0,5&#8211;13 lat. WYNIKI. Po okresie obserwacji 4,4 &plusmn; 3,1 i 5,5 &plusmn; 3,4 lat u 79 (31%) osób, u których początkowo występowała NGT, rozwinęła się IGT, a u 64 (44%) osób z początkową IGT rozwinęła się cukrzyca. Analiza statystyczna przeprowadzona z uwzględnieniem wieku, płci i zawartości procentowej tłuszczu wskazała na niskie M i niskie AIR jako niezależne czynniki określające ryzyko przejścia od NGT do IGT (względne ryzyko [95% CI] dla 10. vs 90. percentyla: M 2,4 [1,2&#8211;4,7], p < 0,02; AIR 2,1 [1,1&#8211;4,1], p < 0,04), a dla przejścia IGT w cukrzycę (M 2,5 [1,3&#8211;5,0], p < 0,01; AIR 1,8 [0,99&#8211;3,3], p = 0,055). WNIOSKI. Zarówno zaburzenia w działaniu, jak i upośledzenie wydzielania insuliny są niezależnymi czynnikami zapowiadającymi pogorszenie tolerancji glukozy na każdym etapie rozwoju cukrzycy i oba powinny stanowić cel prewencji pierwotnej cukrzycy typu 2.OBJECTIVE. Although prospective studies indicate that insulin resistance and insulin secretory dysfunction predict type 2 diabetes, they provide limited information on the relative contributions of both abnormalities to worsening glucose tolerance at different developmental stages of the disease. We therefore assessed the predictive effect of insulin resistance and insulin secretory dysfunction separately for the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and from IGT to diabetes. RESEARCH DESIGN AND METHODS. Insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp), acute insulin secretory response (AIR) (25-g intravenous glucose tolerance test), and body composition (hydrodensitometry or dual-energy X-ray absorptiometry) were measured in 254 Pima Indians with NGT and in 145 Pima Indians with IGT, who were then followed for 0.5&#150;13 years. RESULTS. After follow-ups of 4.4 &#177; 3.1 and 5.5 &#177; 3.4 years, 79 (31%) of the subjects with initial NGT had developed IGT, and 64 (44%) of the subjects with initial IGT had developed diabetes. In proportional-hazards analyses with adjustment for age, sex, and percent body fat, low M and low AIR were independent predictors of both the progression from NGT to IGT (relative hazards [95% CI] for 10th vs. 90th percentile: M2.4 [1.2&#150;4.7], P < 0.02; AIR 2.1 [1.1&#150;4.1], P < 0.04) and from IGT to diabetes (M2.5 [1.3&#150;5.0], P < 0.01; AIR 1.8 [0.99&#150;3.3], P = 0.055). CONCLUSIONS. During each stage of the development of type 2 diabetes, insulin resistance and insulin secretory dysfunction are independent predictors of worsening glucose tolerance and are, therefore, both targets for the primary prevention of the disease

Chronic kidney disease in type 1 diabetes:translation of novel type 2 diabetes therapeutics to individuals with type 1 diabetes

Current management of chronic kidney disease (CKD) in type 1 diabetes centres on glycaemic control, renin–angiotensin system inhibition and optimisation of risk factors including blood pressure, lipids and body weight. While these therapeutic approaches have significantly improved outcomes among people with type 1 diabetes and CKD, this population remains at substantial elevated risk for adverse kidney and cardiovascular events, with limited improvements over the last few decades. The significant burden of CKD and CVD in type 1 diabetes populations highlights the need to identify novel therapies with the potential for heart and kidney protection. Over the last decade, sodium–glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists have emerged as potent kidney-protective and/or cardioprotective agents in type 2 diabetes. The consistent, substantial kidney and cardiovascular benefits of these agents has led to their incorporation into professional guidelines as foundational care for type 2 diabetes. Furthermore, introduction of these agents into clinical practice has been accompanied by a shift in the focus of diabetes care from a ‘glucose-centric’ to a ‘cardiorenal risk-centric’ approach. In this review, we evaluate the potential translation of novel type 2 diabetes therapeutics to individuals with type 1 diabetes with the lens of preventing the development and progression of CKD.</p

Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Alogliptin in Patients With Type 2 Diabetes and Inadequate Glycemic Control: A randomized, double-blind, placebo-controlled study

OBJECTIVE—To evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin in drug-naïve patients with inadequately controlled type 2 diabetes

Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts

© 2018 by the American Diabetes Association. OBJECTIVE: To describe baseline characteristics of the Vitamin D and Type 2 Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association (ADA) criteria for prediabetes.RESEARCH DESIGN AND METHODS: This is a multicenter (n = 22 sites), randomized, double-blind, placebo-controlled, primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol (D3) compared with placebo on incident diabetes in U.S. adults at risk for diabetes. Eligible participants were at risk for diabetes, defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100-125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load 140-199 mg/dL, and/or a hemoglobin A1c (HbA1c) 5.7-6.4% (39-46 mmol/mol).RESULTS: A total of 2,423 participants (45% of whom were women and 33% nonwhite) were randomized to cholecalciferol or placebo. Mean (SD) age was 59 (9.9) years and BMI 32 (4.5) kg/m2. Thirty-five percent met all three prediabetes criteria, 49% met the FPG/HbA1c criteria only, 9.5% met the 2hPG/FPG criteria only, and 6.3% met the 2hPG/HbA1c criteria only. Black participants had the highest mean HbA1c and lowest FPG concentration compared with white, Asian, and other races (P \u3c 0.01); 2hPG concentration did not differ among racial groups. When compared with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG concentration but similar HbA1c and FPG concentrations.CONCLUSIONS: D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria

Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10)

AIM: To compare the associations between concomitant liraglutide use versus no liraglutide use and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among patients receiving basal insulin (either insulin degludec [degludec] or insulin glargine 100 units/mL [glargine U100]) in the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE). MATERIALS AND METHODS: Patients with type 2 diabetes and high cardiovascular risk were randomized 1:1 to degludec or glargine U100. Hazard ratios for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time-varying liraglutide use at any time during the trial, without interaction. Sensitivity analyses were adjusted for baseline covariates including, but not limited to, age, sex, smoking and prior cardiovascular disease. RESULTS: At baseline, 436/7637 (5.7%) patients were treated with liraglutide; after baseline, 187/7637 (2.4%) started and 210/7637 (2.7%) stopped liraglutide. Mean liraglutide exposure from randomization was 530.2 days. Liraglutide use versus no liraglutide use was associated with significantly lower hazard rates for MACE [0.62 (0.41; 0.92)95%CI ] and all-cause mortality [0.50 (0.29; 0.88)95%CI ]. There was no significant difference in the rate of severe hypoglycaemia with versus without liraglutide use. Multiple sensitivity analyses yielded similar results. CONCLUSIONS: Use of liraglutide was associated with significantly lower risk of MACE and death in patients with type 2 diabetes and high cardiovascular risk using basal insulin

LOFAR MSSS: The Scaling Relation between AGN Cavity Power and Radio Luminosity at Low Radio Frequencies

This article has been accepted for publication in a forthcoming issue of Astronomy & Astrophysics. Reproduced with permission from Astronomy & Astrophysics. © 2018 ESO.We present a new analysis of the widely used relation between cavity power and radio luminosity in clusters of galaxies with evidence for strong AGN feedback. We study the correlation at low radio frequencies using two new surveys - the First Alternative Data Release of the TIFR GMRT Sky Survey (TGSS ADR1) at 148 MHz and LOFAR's first all-sky survey, the Multifrequency Snapshot Sky Survey (MSSS) at 140 MHz. We find a scaling relation $P_{\rm cav} \propto L_{148}^{\beta}$, with a logarithmic slope of $\beta = 0.51 \pm 0.14$, which is in good agreement with previous results based on data at 327 MHz. The large scatter present in this correlation confirms the conclusion reached at higher frequencies that the total radio luminosity at a single frequency is a poor predictor of the total jet power. We show that including measurements at 148 MHz alone is insufficient to reliably compute the bolometric radio luminosity and reduce the scatter in the correlation. For a subset of four well-resolved sources, we examine the detected extended structures at low frequencies and compare with the morphology known from higher frequency images and Chandra X-ray maps. In Perseus we discuss details in the structures of the radio mini-halo, while in the 2A 0335+096 cluster we observe new diffuse emission associated with multiple X-ray cavities and likely originating from past activity. For A2199 and MS 0735.6+7421, we confirm that the observed low-frequency radio lobes are confined to the extents known from higher frequencies. This new low-frequency analysis highlights the fact that existing cavity power to radio luminosity relations are based on a relatively narrow range of AGN outburst ages. We discuss how the correlation could be extended using low frequency data from the LOFAR Two-metre Sky Survey (LoTSS) in combination with future, complementary deeper X-ray observations.Peer reviewe

Day-to-day fasting glycaemic variability in DEVOTE: associations with severe hypoglycaemia and cardiovascular outcomes (DEVOTE 2)

AIMS/HYPOTHESIS: The Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) was a double-blind, randomised, event-driven, treat-to-target prospective trial comparing the cardiovascular safety of insulin degludec with that of insulin glargine U100 (100 units/ml) in patients with type 2 diabetes at high risk of cardiovascular events. This paper reports a secondary analysis investigating associations of day-to-day fasting glycaemic variability (pre-breakfast self-measured blood glucose [SMBG]) with severe hypoglycaemia and cardiovascular outcomes. METHODS: In DEVOTE, patients with type 2 diabetes were randomised to receive insulin degludec or insulin glargine U100 once daily. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In this article, day-to-day fasting glycaemic variability was based on the standard deviation of the pre-breakfast SMBG measurements. The variability measure was calculated as follows. Each month, only the three pre-breakfast SMBG measurements recorded before contact with the site were used to determine a day-to-day fasting glycaemic variability measure for each patient. For each patient, the variance of the three log-transformed pre-breakfast SMBG measurements each month was determined. The standard deviation was determined as the square root of the mean of these monthly variances and was defined as day-to-day fasting glycaemic variability. The associations between day-to-day fasting glycaemic variability and severe hypoglycaemia, MACE and all-cause mortality were analysed for the pooled trial population with Cox proportional hazards models. Several sensitivity analyses were conducted, including adjustments for baseline characteristics and most recent HbA1c. RESULTS: Day-to-day fasting glycaemic variability was significantly associated with severe hypoglycaemia (HR 4.11, 95% CI 3.15, 5.35), MACE (HR 1.36, 95% CI 1.12, 1.65) and all-cause mortality (HR 1.58, 95% CI 1.23, 2.03) before adjustments. The increased risks of severe hypoglycaemia, MACE and all-cause mortality translate into 2.7-, 1.2- and 1.4-fold risk, respectively, when a patient's day-to-day fasting glycaemic variability measure is doubled. The significant relationships of day-to-day fasting glycaemic variability with severe hypoglycaemia and all-cause mortality were maintained after adjustments. However, the significant association with MACE was not maintained following adjustment for baseline characteristics with either baseline HbA1c (HR 1.19, 95% CI 0.96, 1.47) or the most recent HbA1c measurement throughout the trial (HR 1.21, 95% CI 0.98, 1.49). CONCLUSIONS/INTERPRETATION: Higher day-to-day fasting glycaemic variability is associated with increased risks of severe hypoglycaemia and all-cause mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT01959529