RESUMEN

AIMS: To evaluate the safety and efficacy of once-weekly dulaglutide 1.5 mg, a long-acting glucagon-like peptide-1 receptor agonist, compared with placebo in patients with type 2 diabetes (T2D) on glimepiride monotherapy. METHODS: This phase III, randomized (4 : 1; dulaglutide:placebo), double-blind, placebo-controlled, 24-week study compared the safety and efficacy of once-weekly dulaglutide 1.5 mg with placebo in sulphonylurea-treated (≥half-maximal dose, stable ≥3 months) patients (N = 300) with T2D and inadequate glycaemic control [glycated haemoglobin (HbA1c) ≥7.5 and ≤9.5% (≥58 mmol/mol and ≤80 mmol/mol)]. Analysis was carried out according to intention-to-treat. RESULTS: At baseline, the mean participant age was 58 years; mean HbA1c was 8.4% (68 mmol/mol) and mean weight was 85.5 kg. Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between-group HbA1c difference of -1.3% [95% confidence interval (CI) -1.6, -1.0] or -14 mmol/mol (95% CI -17, -11); p < 0.001. A greater proportion of participants in the dulaglutide group reached an HbA1c level of <7.0% (53 mmol/mol) compared with placebo (55.3% vs 18.9%; p < 0.001). Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo (between-group difference -1.86 mmol/l (95% CI -2.58, -1.14) or -33.54 mg/dl (95% CI -46.55, -20.53); p < 0.001. Weight was decreased significantly from baseline in the dulaglutide group (p < 0.001); the between-group difference was not significant. The most common treatment-emergent adverse events for dulaglutide 1.5 mg were gastrointestinal: nausea (10.5%), diarrhoea (8.4%) and eructation (5.9%). Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo (2.37 and 0.07 events/participant/year, respectively; p = 0.025). No severe hypoglycaemia was reported. CONCLUSIONS: Once-weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy.

Asunto(s)

Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/análogos & derivados , Hiperglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Método Doble Ciego , Esquema de Medicación , Resistencia a Medicamentos , Quimioterapia Combinada/efectos adversos , Femenino , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Inyecciones Subcutáneas , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Compuestos de Sulfonilurea/efectos adversos

RESUMEN

We present an extension of cluster perturbation theory to include many-body correlations associated with local e-e repulsion in real materials. We show that this approach can describe the physics of complex correlated materials where different atomic species and different orbitals coexist. The prototypical case of MnO is considered.

Asunto(s)

Compuestos de Manganeso/química , Óxidos/química , Teoría Cuántica , Elementos de Transición/química , Espectroscopía de Fotoelectrones

RESUMEN

We present a new theoretical approach to describe x-ray absorption and magnetic circular dichroism spectra in the presence of electron-electron correlation. Our approach provides an unified picture to include correlations in both charged and neutral excitations, namely in direct/inversion photoemission where electrons are removed/added, and photoabsorption where electrons are promoted from core levels to empty states. We apply this approach to the prototypical case of the L(2, 3) edge of 3d transition metals and we show that the inclusion of many-body effects in the core level excitations is essential to reproduce, together with satellite structures in core level photoemission, the observed asymmetric lineshapes in x-ray absorption and dichroic spectra.

RESUMEN

We present the first time-dependent density functional theory (TDDFT) calculation on a light-harvesting triad carotenoid-diaryl-porphyrin-C(60). Besides the numerical challenge that the ab initio study of the electronic structure of such a large system presents, we show that TDDFT is able to provide an accurate description of the excited-state properties of the system. In particular, we calculate the photoabsorption spectrum of the supramolecular assembly, and we provide an interpretation of the photoexcitation mechanism in terms of the properties of the component moieties. The spectrum is in good agreement with experimental data, and provides useful insight on the photoinduced charge-transfer mechanism which characterizes the system.

Asunto(s)

Carotenoides , Simulación por Computador , Fulerenos , Luz , Modelos Químicos , Porfirinas , Carotenoides/química , Carotenoides/efectos de la radiación , Fulerenos/química , Fulerenos/efectos de la radiación , Sustancias Macromoleculares/química , Sustancias Macromoleculares/efectos de la radiación , Fotoquímica , Porfirinas/química , Porfirinas/efectos de la radiación , Teoría Cuántica , Factores de Tiempo

RESUMEN

The strength of electronic correlation effects in the spin-dependent electronic structure of ferromagnetic bcc Fe(110) has been investigated by means of spin and angle-resolved photoemission spectroscopy. The experimental results are compared to theoretical calculations within the three-body scattering approximation and within the dynamical mean-field theory, together with one-step model calculations of the photoemission process. This comparison indicates that the present state of the art many-body calculations, although improving the description of correlation effects in Fe, give too small mass renormalizations and scattering rates thus demanding more refined many-body theories including nonlocal fluctuations.

RESUMEN

In order to provide a structural basis for a physical understanding of exchange bias in metal/magnetic-oxide interfaces, we have determined the structure of the Fe/NiO(001) interface by means of x-ray absorption spectroscopy and ab initio density functional theory calculations. A Fe-Ni alloyed phase on top of an interfacial FeO planar layer is formed. The FeO layer exhibits a 7% expanded interlayer distance and a 0.3 A buckling; its presence is predicted to increase the spin magnetic moment of the interface Fe atoms by 0.6 mu(B), compared to the ideally abrupt interface.

RESUMEN

We report the inclusion of electron-electron correlation in the calculation of transport properties within an ab initio scheme. A key step is the reformulation of Landauer's approach in terms of an effective transmittance for the interacting electron system. We apply this framework to analyze the effect of short-range interactions on Pt atomic wires and discuss the coherent and incoherent correction to the mean-field approach.

RESUMEN

The intravertebral vacuum cleft sign (VCS) is an uncommon radiological sign, characterized by a radiolucent zone in the vertebral body. It is composed of 95% nitrogen and small amounts of oxygen and carbon dioxide. Post-traumatic ischemic necrosis could be its physiopathological mechanism, along with other pathologies like osteoporosis, corticosteroid therapy, diabetes, arteriosclerosis, alcoholism, multiple myeloma, bone metastasis and osteomyelitis. The broad diagnosis is made by antero-posterior X-ray, but computed tomography scan (CT scan) and magnetic resonance imaging (MRI) may help with the differential diagnosis. The aims of this paper are, on one hand, to communicate the clinical case of a 73-year-old osteoporotic woman with traumatic vertebral fractures who developed this sign in her radiological survey. On the other hand, its secondary aims are to review the medical literature about this sign and to show the clinical and radiological evolution after a percutaneous vertebroplasty.

Asunto(s)

Gases/análisis , Osteoporosis Posmenopáusica/complicaciones , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Anciano , Densidad Ósea , Diagnóstico Diferencial , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Imagen por Resonancia Magnética , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/etiología , Osteoporosis Posmenopáusica/diagnóstico , Osteoporosis Posmenopáusica/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico , Tomografía Computarizada por Rayos X

RESUMEN

The low-energy electronic excitations in cobalt are studied by a theoretical method that includes many-body effects and a realistic description of the band structure. Angle-resolved photoemission spectra measured on a thick film of hexagonal close-packed Co on Cu(111) agree well with calculated spectral functions. Because of many-body effects no sharp quasiparticle peaks exist for binding energies larger than 2 eV and in this energy region the spectrum is essentially incoherent. The many-body corrections are much stronger in the majority-spin channel and drastically affect the spin polarization of the spectra.