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OBJECTIVETo assess the efficacy/safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with glimepiride over 104 weeks in patients with type 2 diabetes inadequately controlled with metformin. RESEARCH DESIGN AND METHODSIn this randomized, double-blind study, patients (N = 1,450) received canagliflozin 100 or 300 mg or glimepiride (titrated up to 6 or 8 mg/day) during a 52-week core period followed by a 52-week extension. RESULTSAt week 104, reductions from baseline in A1C were 20.65%, 20.74%, and 20.55% (27.1, 28.1, and 26.0 mmol/mol) with canagliflozin 100 and 300 mg and glimepiride, respectively. Durability analyses showed sustained A1C lowering with both canagliflozin doses versus glimepiride. Reductions in body weight (24.1%, 24.2%, and 0.9%, respectively) and systolic blood pressure (22.0, 23.1, and 1.7 mmHg, respectively) were seen with canagliflozin 100 and 300 mg compared with glimepiride at week 104. The overall adverse event (AE) incidence was 73.3%, 77.9%, and 78.4% with canagliflozin 100 and 300 mg and glimepiride; the incidence of AE-related discontinuations was low across groups (6.2%, 9.5%, and 7.3%, respectively). Incidences of genital mycotic infections, urinary tract infections, and osmotic diuresis-related AEs were higher with canagliflozin than glimepiride; these were generally mild to moderate in intensity and led to few discontinuations. Fewer patients had hypoglycemia episodes with canagliflozin 100 and 300 mg than glimepiride (6.8%, 8.2%, and 40.9%). Mild decreases in estimated glomerular filtration rate occurred initially with canagliflozin; these attenuated over 104 weeks. CONCLUSIONSCanagliflozin provided durable glycemic improvements compared with glimepiride and was generally well tolerated in patients with type 2 diabetes receiving background treatment with metformin over 104 weeks.

Non-local methods for image denoising and inpainting have gained considerable attention in recent years. This is in part due to their superior performance in textured images, a known weakness of purely local methods. Local methods on the other hand have demonstrated to be very appropriate for the recovering of geometric structures such as image edges. The synthesis of both types of methods is a trend in current research. Variational analysis in particular is an appropriate tool for a unified treatment of local and non-local methods. In this work we propose a general variational framework non-local image inpainting, from which important and representative previous inpainting schemes can be derived, in addition to leading to novel ones. We explicitly study some of these, relating them to previous work and showing results on synthetic and real images.

The introduction of farming had far-reaching impacts on health, social structure and demography. Although the spread of domesticated plants and animals has been extensively tracked, it is unclear how these nascent economies developed within different environmental and cultural settings. Using molecular and isotopic analysis of lipids from pottery, here we investigate the foods prepared by the earliest farming communities of the European Atlantic seaboard. Surprisingly, we find an absence of aquatic foods, including in ceramics from coastal sites, except in the Western Baltic where this tradition continued from indigenous ceramic using hunter-gatherer-fishers. The frequency of dairy products in pottery increased as farming was progressively introduced along a northerly latitudinal gradient. This finding implies that early farming communities needed time to adapt their economic practices before expanding into more northerly areas. Latitudinal differences in the scale of dairy production might also have influenced the evolution of adult lactase persistence across Europe.

Increased levels of TSH are associated to a decrease in HL activity, explaining our findings of an LDL particle rich in TG. This qualitative lipoprotein alteration suggests a pro-atherogenic pattern in sH. Treatment with L-T(4), however, did not correct the basal lipid derangement.