Association of Glycemic Control Trajectory with Short-Term Mortality in Diabetes Patients with High Cardiovascular Risk: a Joint Latent Class Modeling Study

Background: The relationship between risk factor or biomarker trajectories and contemporaneous short-term clinical outcomes is poorly understood. In diabetes patients, it is unknown whether hemoglobin A1c (HbA1c) trajectories are associated with clinical outcomes and can inform care in scenarios in which a single HbA1c is uninformative, for example, after a diagnosis of coronary artery disease (CAD). Objective: To compare associations of HbA1c trajectories and single HbA1c values with short-term mortality in diabetes patients evaluated for CAD Design: Retrospective observational cohort study Participants: Diabetes patients (n = 7780) with and without angiographically defined CAD Main Measures: We used joint latent class mixed models to simultaneously fit HbA1c trajectories and estimate association with 2-year mortality after cardiac catheterization, adjusting for clinical and demographic covariates. Key Results: Three HBA1c trajectory classes were identified: individuals with stable glycemia (class A; n = 6934 [89%]; mean baseline HbA1c 6.9%), with declining HbA1c (class B; n = 364 [4.7%]; mean baseline HbA1c 11.6%), and with increasing HbA1c (class C; n = 482 [6.2%]; mean baseline HbA1c 8.5%). HbA1c trajectory class was associated with adjusted 2-year mortality (3.0% [95% CI 2.8, 3.2] for class A, 3.1% [2.1, 4.2] for class B, and 4.2% [3.4, 4.9] for class C; global P = 0.047, P = 0.03 comparing classes A and C, P > 0.05 for other pairwise comparisons). Baseline HbA1c was not associated with 2-year mortality (P = 0.85; hazard ratios 1.01 [0.96, 1.06] and 1.02 [0.95, 1.10] for HbA1c 7–9% and ≥ 9%, respectively, relative to HbA1c < 7%). The association between HbA1c trajectories and mortality did not differ between those with and without CAD (interaction P = 0.1). Conclusions: In clinical settings where single HbA1c measurements provide limited information, HbA1c trajectories may help stratify risk of complications in diabetes patients. Joint latent class modeling provides a generalizable approach to examining relationships between biomarker trajectories and clinical outcomes in the era of near-universal adoption of electronic health records

Breaking of general rotational symmetries by multi-dimensional classical ratchets

We demonstrate that a particle driven by a set of spatially uncorrelated, independent colored noise forces in a bounded, multidimensional potential exhibits rotations that are independent of the initial conditions. We calculate the particle currents in terms of the noise statistics and the potential asymmetries by deriving an n-dimensional Fokker-Planck equation in the small correlation time limit. We analyze a variety of flow patterns for various potential structures, generating various combinations of laminar and rotational flows.Comment: Accepted, Physical Review

Effective knowledge translation approaches and practices in Indigenous health research: A systematic review protocol

Background: Effective knowledge translation (KT) is critical to implementing program and policy changes that require shared understandings of knowledge systems, assumptions, and practices. Within mainstream research institutions and funding agencies, systemic and insidious inequities, privileges, and power relationships inhibit Indigenous peoples' control, input, and benefits over research. This systematic review will examine literature on KT initiatives in Indigenous health research to help identify wise and promising Indigenous KT practices and language in Canada and abroad. Methods: Indexed databases including Aboriginal Health Abstract Database, Bibliography of Native North Americans, CINAHL, Circumpolar Health Bibliographic Database, Dissertation Abstracts, First Nations Periodical Index, Medline, National Indigenous Studies Portal, ProQuest Conference Papers Index, PsycInfo, Social Services Abstracts, Social Work Abstracts, and Web of Science will be searched. A comprehensive list of non-indexed and grey literature sources will also be searched. For inclusion, documents must be published in English; linked to Indigenous health and wellbeing; focused on Indigenous people; document KT goals, activities, and rationale; an

Biodistribution of 64 Cu in Inflamed Rats Following Administration of Two Anti-Inflammatory Copper Complexes

64Cu was administered in two anti-inflammatory formulations to normal rats and to rats with 2 forms of local inflammation, namely (a) an acute paw oedema (elicited with carrageenan) or (b) a chronic granulomatous response to an implanted irritant (Mycobacterium tuberculosis in a polyurethane sponge). The copper formulations used were (i) a slow release one consisting of Cu(II) salicylate applied dermally with ethanol/DMSO and (ii) short acting hydrophilic complex (Cu(I)Cu(II)-penicillamine)5- given subcutaneously. Three types of changes in copper biodistribution with these forms of inflammation were discerned based on determination of 64Cu and copper content in the following organs: inflammatory locus (foot or sponge implant), kidney, liver, spleen, adrenals, brain, blood, thymus, heart, and skin (site of application). The most evident changes were in the kidneys, liver, spleen, adrenals, thymus and serum from animals with chronic granulomatous inflammation. In contrast, a short term acute inflammatory stress (carrageenan paw oedema) had little effect. While copper D-penicillamine (applied subcutaneously) appeared to move as a bolus through the animals, the results with the percutaneous copper salicylate formulation are consistent with it providing a slow release source of copper(II). Exogenous 64Cu from both formulations was sequestered at inflammatory sites (relative to serum). This may partly explain how applied copper complexes can be anti-inflammatory

Interactions between domestic and wild carnivores around the greater Serengeti ecosystem

The domestic and wild carnivore interface is complex, yet understudied. Interactions between carnivore species have important implications for direct interference competition, cross‐species transmission of shared pathogens and conservation threats to wild carnivores. However, carnivore intraguild interactions are hard to quantify. In this study, we asked 512 villagers residing around a conservation area in the Serengeti Ecosystem, Tanzania, to report on the presence of wild carnivores in their village, the number of domestic dogs Canis familiaris and cats Felis catus in their household and interactions between domestic and wild carnivores. Wild carnivores are abundant near households surrounding the Serengeti National Park, villagers have many free‐ranging domestic dogs (and would like to have more) and direct and indirect contacts between wild and domestic carnivores are common. Large carnivores, such as spotted hyenas and leopards, often killed or wounded domestic dogs. Small carnivores, such as mongoose, bat‐eared fox, serval and wildcat, are locally abundant and frequently interact with domestic dogs. We demonstrate that interspecific carnivore behavior, human culture and local and regional geography play a complex role in domestic and wild carnivore interaction risk around conservation areas. Through the use of household surveys, we were able to efficiently obtain data on a wide scope of carnivore interactions over a large area, which may provide a direction for future targeted and in‐depth research to reduce interspecific conflict. Improving the health and husbandry of domestic animals and reducing the unintentional feeding of wild carnivores could reduce dog–wildlife interactions and the potential for pathogen transmission at the domestic–wild animal interface