Switching to Once-Daily Liraglutide From Twice-Daily Exenatide Further Improves Glycemic Control in Patients With Type 2 Diabetes Using Oral Agents

OBJECTIVETo evaluate efficacy and safety of switching from twice-daily exenatide to once-daily liraglutide or of 40 weeks of continuous liraglutide therapy.RESEARCH DESIGN AND METHODSWhen added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1C, fasting plasma glucose, and the homeostasis model of β-cell function (HOMA-B) than exenatide, with less persistent nausea and hypoglycemia. In this 14-week extension of LEAD-6, patients switched from 10 μg twice-daily exenatide to 1.8 mg once-daily liraglutide or continued liraglutide.RESULTSSwitching from exenatide to liraglutide further and significantly reduced A1C (0.32%), fasting plasma glucose (0.9 mmol/l), body weight (0.9 kg), and systolic blood pressure (3.8 mmHg) with minimal minor hypoglycemia (1.30 episodes/patient-year) or nausea (3.2%). Among patients continuing liraglutide, further significant decreases in body weight (0.4 kg) and systolic blood pressure (2.2 mmHg) occurred with 0.74 episodes/patient-year of minor hypoglycemia and 1.5% experiencing nausea.CONCLUSIONSConversion from exenatide to liraglutide is well tolerated and provides additional glycemic control and cardiometabolic benefits

Testing data types implementations from algebraic specifications

Algebraic specifications of data types provide a natural basis for testing data types implementations. In this framework, the conformance relation is based on the satisfaction of axioms. This makes it possible to formally state the fundamental concepts of testing: exhaustive test set, testability hypotheses, oracle. Various criteria for selecting finite test sets have been proposed. They depend on the form of the axioms, and on the possibilities of observation of the implementation under test. This last point is related to the well-known oracle problem. As the main interest of algebraic specifications is data type abstraction, testing a concrete implementation raises the issue of the gap between the abstract description and the concrete representation. The observational semantics of algebraic specifications bring solutions on the basis of the so-called observable contexts. After a description of testing methods based on algebraic specifications, the chapter gives a brief presentation of some tools and case studies, and presents some applications to other formal methods involving datatypes

A polymorphism in the gene encoding carnosinase (CNDP1) as a predictor of mortality and progression from nephropathy to end-stage renal disease in type 1 diabetes mellitus

Aims/hypothesis Homozygosity for a five leucine repeat (5L-5L) in the carnosinase gene (CNDP1) has been found to be cross-sectionally associated with a low frequency of diabetic nephropathy (DN), mainly in type 2 diabetes. We prospectively investigated in patients with type I diabetes whether: (1) 5L-5L is associated with mortality; (2) there is an interaction of 5L-5L with DN or sex for prediction of mortality; and (3) 5L-5L is associated with progression to end-stage renal disease (ESRD). Methods In this prospective study in white European patients with type 1 diabetes, individuals with DN were defined by persistent albuminuria >= 300 mg/24 h. Controls without nephropathy were defined by persistent (>15 years) normoalbuminuria Results The study involved 916 patients with DN and 1,170 controls. During follow-up for 8.8 years, 107 patients (14%) with 5L-5L died compared with 182 patients (13.8%) with other genotypes (p=0.99). There was no significant interaction of 5L-5L with DN for prediction of mortality (p=0.57), but a trend towards interaction with sex (p=0.08). In patients with DN, HR for ESRD in 5L-5L vs other genotypes was not constant over time, with increased risk for 5L-5L beyond 8 years of follow-up (p=0.03). Conclusions/interpretation CNDP1 polymorphism was not associated with mortality, and nor was there an interaction of this polymorphism with DN for prediction of mortality in patients with type 1 diabetes. CNDP1 polymorphism predicts progression to ESRD in patients with DN, but only late after baseline measurements

The words leader/líder and their resonances in an Italo-Latin American multinational corporation

© 2017, © The Author(s) 2017. The problems of ‘lost in translation’ are well known. Yet some terms of English managerial vocabulary, which are perfectly translatable in other languages, remain untranslated. One explanation of this phenomenon is what Linguistic anthropology call negative semantic resonances. Semantic resonances focused on the issue of which meanings can or cannot be expressed by a single word in different cultures. In this paper, based on an organisational ethnography of Latin American expatriates working for an Italo-Latin-American multinational corporation (Tubworld), we analyse the resonances of the word leader/líder and director, direttore, capo, guida, coordinador, caudillo among a group of expatriates; all Italian, Spanish or multilingual speakers who use English as a second language in their everyday interactions. The paper explains how the different uses contribute to create a meaning of what a leader should and should not be; someone who leads without leading, sometimes a manager. The authors, an Italian native speaker who learnt Spanish during childhood and use English as his everyday language and a Spanish native speaker, argue that Italian or Spanish speakers not only avoid the words duce and caudillo (the vernacular vocabulary for leader, not in use due to the political and cultural meaning) but also the word leader/líder itself, as it resonate to the other two (violent, authoritarian, autocratic, antidemocratic leadership) but furthermore because the word, a lexical loan from English, failed to encapsulate the complexity of leading multilingual organisations like Tubworld

A discrete time neural network model with spiking neurons II. Dynamics with noise

We provide rigorous and exact results characterizing the statistics of spike trains in a network of leaky integrate and fire neurons, where time is discrete and where neurons are submitted to noise, without restriction on the synaptic weights. We show the existence and uniqueness of an invariant measure of Gibbs type and discuss its properties. We also discuss Markovian approximations and relate them to the approaches currently used in computational neuroscience to analyse experimental spike trains statistics.Comment: 43 pages - revised version - to appear il Journal of Mathematical Biolog

Nod2 Suppresses Borrelia burgdorferi Mediated Murine Lyme Arthritis and Carditis through the Induction of Tolerance

The internalization of Borrelia burgdorferi, the causative agent of Lyme disease, by phagocytes is essential for an effective activation of the immune response to this pathogen. The intracellular, cytosolic receptor Nod2 has been shown to play varying roles in either enhancing or attenuating inflammation in response to different infectious agents. We examined the role of Nod2 in responses to B. burgdorferi. In vitro stimulation of Nod2 deficient bone marrow derived macrophages (BMDM) resulted in decreased induction of multiple cytokines, interferons and interferon regulated genes compared with wild-type cells. However, B. burgdorferi infection of Nod2 deficient mice resulted in increased rather than decreased arthritis and carditis compared to control mice. We explored multiple potential mechanisms for the paradoxical response in in vivo versus in vitro systems and found that prolonged stimulation with a Nod2 ligand, muramyl dipeptide (MDP), resulted in tolerance to stimulation by B. burgdorferi. This tolerance was lost with stimulation of Nod2 deficient cells that cannot respond to MDP. Cytokine patterns in the tolerance model closely paralleled cytokine profiles in infected Nod2 deficient mice. We propose a model where Nod2 has an enhancing role in activating inflammation in early infection, but moderates inflammation after prolonged exposure to the organism through induction of tolerance

RELAÇÕES ENTRE PODER E SUBJETIVIDADE EM UMA ORGANIZAÇÃO FAMILIAR

Neste artigo, o objetivo é discutir os vínculos entre indivíduo e organização, que caracterizam a permanência, ou não, de sujeitos indicados como sucessores na empresa da família, tendo como base de análise as categorias inter-relacionadas de subjetividade e poder. Tal propósito originou uma pesquisa qualitativa, na qual o foco foram as histórias de vida dos três filhos do fundador de uma empresa familiar. No tratamento dos dados, foi usada a técnica da análise do discurso para a identificação das estratégias discursivas usadas pelos entrevistados em seus depoimentos, tendo elas sido agrupadas em duas categorias discursivas: histórias sobre o trabalho e histórias sobre a família. Na primeira categoria, a partir do mito do herói fundador, a história sobre o trabalho é romanceada, em um processo que, por meio da socialização primária, esconde o controle por intermédio da inserção de valores do pai na precoce entrada na empresa por parte dos filhos do sexo masculino. Sobre a família, os depoimentos sugerem que a empresa é sua continuação; sendo estendidos, ao negócio, os laços familiares. A empresa liga, simbólica e afetivamente, os fi lhos ao legado do pai, o que a torna um projeto de vida reapropriado e realimentado por eles. As conclusões alertam que as empresas familiares não deixam de ser empreendimentos econômicos mesmo sendo intensas em afetividade, sendo os filhos vítimas dos mesmos estratagemas que diversos autores denunciam em empresas capitalistas por aderirem a um sonho que não lhes pertence, mas que lhes cabe manter vivo