Uniform topologies on types

10.3982/TE462Theoretical Economics53445-47

A study to assess the unmet medical needs associated with the use of basal insulin in patients with type 2 diabetes

Aim: To describe in a real-world setting, the proportion of patients with a symptomatic hypoglycaemic event and the proportion of individuals with type 2 diabetes, who newly or recently initiated with basal insulin, achieving individual or general HbA1c target. Materials and Method: DINAS-AR was a national prospective observational study to assess the unmet needs in patients with type 2 diabetes treated with basal insulin with or without oral antihyperglycaemic drugs and/or GLP-1 receptor agonist. The study was conducted at 19 hospitals. Results: A total of 385 uncontrolled patients (≥18 years) who recently initiated basal insulin or who initiated treatment within a year prior to study enrolment entered the study. Outcomes were follow-up incidence of hypoglycaemic events, change of HbA1C and achievement of HBA1c <7% or individual target. A total of 44 patients (11.9%) reported the occurrence of ≥1 symptomatic hypoglycaemia event(s). HbA1c reductions were greater in patients who had recently initiated treatment with basal insulin (between 15 and 90 days prior to study entry) vs patients who initiated treatment within 1 year. A total of 80 patients (31.6%) achieved individual HbA1c target (or target <7.0%) at Week 24. Furthermore, the proportion of patients achieving this target without symptomatic hypoglycaemia was 26.1% (n = 66). A lower percentage of glycemia target achievement was observed in patients reporting hypoglycaemia (n = 14), 20.6% of all patients reporting hypoglycaemia event(s) vs (n = 66) 35.7% of all patients without hypoglycaemia event reported. Conclusion: In this real-world study, although the hypoglycaemia rate was not high in adults with type 2 diabetes treated with insulin, there was a lower percentage of patients that achieved glycemic target among those reporting hypoglycaemia events vs patients who did not report them.Fil: Frechtel, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Forti, Lujan. Sanofi Aventis Argentina Sociedad Anonima.; ArgentinaFil: Faingold, María Cristina. Unidad Asistencial "Dr. César Milstein"; ArgentinaFil: Perez Mangui, Federico. Centro de Investigaciones Metabólicas; ArgentinaFil: Orio, Silvia. No especifíca;Fil: Issa, Claudia. Sanatorio Guemes Sociedad Anonima.; ArgentinaFil: Guaita, María Silvina. Sanofi Aventis Argentina Sociedad Anonima.; ArgentinaFil: Vivas, Norma. Sanofi Aventis Argentina Sociedad Anonima.; ArgentinaFil: De Luca, Julian A.. Sanofi Aventis Argentina Sociedad Anonima.; Argentin

WDR19 : An ancient, retrograde, intraflagellar ciliary protein is mutated in autosomal recessive retinitis pigmentosa and in Senior‐Loken syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99013/1/cge12196.pd

Recomendaciones para gestantes con diabetes: conclusiones del Consenso reunido por convocatoria del Comité de Diabetes y Embarazo de la SAD

La diabetes gestacional es una alteración de la tolerancia a la glucosa con severidad variable que comienza o es reconocida por primera vez durante el embarazo en curso. Esta definición es válida independientemente del tratamiento que requiera, de si se trata de una diabetes previa al embarazo que no fue diagnosticada, o si la alteración del metabolismo hidrocabonado persiste al concluir la gestación. El presente trabajo, realizado por Consenso en el Comité de Diabetes y Embarazo de la Sociedad Argentina de Diabetes, actualiza los criterios diagnósticos de la diabetes gestacional, así como también el tratamiento, seguimiento y control de la patología tanto durante la gestación, como en el parto y el puerperio.Fil: Faingold, María Cristina.Fil: Lamela, C..Fil: Gheggi, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lapertosa, Silvia.Fil: Di Marco, Ingrid.Fil: Basualdo, María Natalia.Fil: Rovira, Marta Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Glatstein, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: López, C..Fil: Caamaño, A..Fil: Salcedo, L..Fil: Rodríguez, María Elena.Fil: Alvariñas J.

Homogenized stiffness matrices for mineralized collagen fibrils and lamellar bone using unit cell finite element models

Mineralized collagen fibrils have been usually analyzed like a two phase composite material where crystals are considered as platelets that constitute the reinforcement phase. Different models have been used to describe the elastic behavior of the material. In this work, it is shown that, when Halpin-Tsai equations are applied to estimate elastic constants from typical constituent properties, not all crystal dimensions yield a model that satisfy thermodynamic restrictions. We provide the ranges of platelet dimensions that lead to positive definite stiffness matrices. On the other hand, a finite element model of a mineralized collagen fibril unit cell under periodic boundary conditions is analyzed. By applying six canonical load cases, homogenized stiffness matrices are numerically calculated. Results show a monoclinic behavior of the mineralized collagen fibril. In addition, a 5-layer lamellar structure is also considered where crystals rotate in adjacent layers of a lamella. The stiffness matrix of each layer is calculated applying Lekhnitskii transformations and a new finite lement model under periodic boundary conditions is analyzed to calculate the homogenized 3D anisotropic stiffness matrix of a unit cell of lamellar bone. Results are compared with the rule-of-mixtures showing in general good agreement.The authors acknowledge the Ministerio de Economia y Competitividad the financial support given through the project DPI2010-20990 and the Generalitat Valenciana through the Programme Prometeo 2012/023. The authors thank Ms. Carla Gonzalez Carrillo by her help in the development of some of the numerical models.Vercher Martínez, A.; Giner Maravilla, E.; Arango Villegas, C.; Tarancón Caro, JE.; Fuenmayor Fernández, FJ. (2014). Homogenized stiffness matrices for mineralized collagen fibrils and lamellar bone using unit cell finite element models. Biomechanics and Modeling in Mechanobiology. 13(2):1-21. https://doi.org/10.1007/s10237-013-0507-yS121132Akiva U, Wagner HD, Weiner S (1998) Modelling the three-dimensional elastic constants of parallel-fibred and lamellar bone. J Mater Sci 33:1497–1509Ascenzi A, Bonucci E (1967) The tensile properties of single osteons. Anat Rec 158:375–386Ascenzi A, Bonucci E (1968) The compressive properties of single osteons. Anat Rec 161:377–392Ashman RB, Cowin SC, van Buskirk WC, Rice JC (1984) A continuous wave technique for the measurement of the elastic properties of cortical bone. J Biomech 17:349–361Bar-On B, Wagner HD (2012) Elastic modulus of hard tissues. J Biomech 45:672–678Bondfield W, Li CH (1967) Anisotropy of nonelastic flow in bone. J Appl Phys 38:2450–2455Cowin SC (2001) Bone mechanics handbook, 2nd edn. CRC Press Boca Raton, FloridaCowin SC, van Buskirk WC (1986) Thermodynamic restrictions on the elastic constant of bone. J Biomech 19:85–86Currey JD (1962) Strength of bone. 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Polym Eng Sci 13:139–145Martínez-Reina J, Domínguez J, García-Aznar JM (2011) Effect of porosity and mineral content on the elastic constants of cortical bone: a multiscale approach. Biomech Model Mechanobiol 10:309–322Orgel JPRO, Miller A, Irving TC, Fischetti RF, Hammersley AP, Wess TJ (2001) The in situ supermolecular structure of type I collagen. Structure 9:1061–1069Padawer GE, Beecher N (1970) On the strength and stiffness of planar reinforced plastic resins. Polym Eng Sci 10:185–192Pahr DH, Rammerstofer FG (2006) Buckling of honeycomb sandwiches: periodic finite element considerations. Comput Model Eng Sci 12:229–242Reisinger AG, Pahr DH, Zysset PK (2010) Sensitivity analysis and parametric study of elastic properties of an unidirectional mineralized bone fibril-array using mean field methods. Biomech Model Mechanobiol 9:499–510Reisinger AG, Pahr DH, Zysset PK (2011) Elastic anisotropy of bone lamellae as a function of fibril orientation pattern. Biomech Model Mechanobiol 10:67–77Rezkinov N, Almany-Magal R, Shahar R, Weiner S (2013) Three-dimensional imaging of collagen fibril organization in rat circumferential lamellar bone using a dual beam electron microscope reveals ordered and disordered sub-lamellar structures. Bone 52(2):676–683Rho JY, Kuhn-Spearing L, Zioupos P (1998) Mechanical properties and the hierarchical structure of bone. Med Eng Phys 20:92–102Rubin MA, Jasiuk I, Taylor J, Rubin J, Ganey T, Apkarian RP (2003) TEM analysis of the nanostructure of normal and osteoporotic human trabecular bone. Bone 33:270–282Suquet P (1987) Lecture notes in physics-homogenization techniques for composite media. Chapter IV. Springer, BerlinWagermaier W, Gupta HS, Gourrier A, Burghammer M, Roschger P, Fratzl P (2006) Spiral twisting of fiber orientation inside bone lamellae. Biointerphases 1:1–5Wagner HD, Weiner S (1992) On the relationship between the microstructure of bone and its mechanical stiffness. J Biomech 25:1311–1320Weiner S, Wagner HD (1998) The material bone: structure-mechanical function relations. Annu Rev Mater Sci 28:271–298Weiner S, Traub W, Wagner H (1999) Lamellar bone: structure-function relations. J Struct Biol 126:241–255Yao H, Ouyang L, Ching W (2007) Ab initio calculation of elastic constants of ceramic crystals. J Am Ceram 90:3194–3204Yoon YJ, Cowin SC (2008b) The estimated elastic constants for a single bone osteonal lamella. Biomech Model Mechanobiol 7:1–11Yuan F, Stock SR, Haeffner DR, Almer JD, Dunand DC, Brinson LC (2011) A new model to simulate the elastic properties of mineralized collagen fibril. Biomech Model Mechanobiol 10:147–160Zhang Z, Zhang YWF, Gao H (2010) On optimal hierarchy of load-bearing biological materials. Proc R Soc B 278:519–525Zuo S, Wei Y (2007) Effective elastic modulus of bone-like hierarchical materials. Acta Mechanica Solida Sinica 20:198–20

Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach

[EN] In this work, explicit expressions to estimate all the transversely isotropic elastic constants of lamellar bone as a function of the volumetric bone mineral density (BMD) are provided. The methodology presented is based on the direct homogenization procedure using the finite element method, the continuum approach based on the Hill bounds, the least-square method and the mean field technique. Firstly, a detailed description of the volumetric content of the different components of bone is provided. The parameters defined in this step are related to the volumetric BMD considering that bone mineralization process occurs at the smallest scale length of the bone tissue. Then, a thorough description provides the details of the numerical models and the assumptions adopted to estimate the elastic behaviour of the forward scale lengths. The results highlight the noticeable influence of the BMD on the elastic modulus of lamellar bone. Power law regressions fit the Young's moduli, shear stiffness moduli and Poisson ratios. In addition, the explicit expressions obtained are applied to the estimation of the elastic constants of cortical bone. At this scale length, a representative unit cell of cortical bone is analysed including the fibril orientation pattern given by Wagermaier et al. (Biointerphases 1:1-5, 2006) and the BMD distributions observed by Granke et al. (PLoS One 8:e58043, 2012) for the osteon. Results confirm that fibril orientation arrangement governs the anisotropic behaviour of cortical bone instead of the BMD distribution. The novel explicit expressions obtained in this work can be used for improving the accuracy of bone fracture risk assessment.The authors acknowledge the Ministerio de Economia y Competitividad for the financial support received through the project DPI2013-46641-R and to the Generalitat Valenciana for Programme PROMETEO 2016/007. The authors declare that they have no conflict of interestVercher Martínez, A.; Giner Maravilla, E.; Belda, R.; Aigoun, A.; Fuenmayor Fernández, F. (2018). Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach. Biomechanics and Modeling in Mechanobiology. 17(2):449-464. https://doi.org/10.1007/s10237-017-0971-xS449464172Akiva U, Wagner HD, Weiner S (1998) Modelling the three-dimensional elastic constants of parallel-fibred and lamellar bone. J Mater Sci 33:1497–1509Ascenzi A, Bonucci E (1967) The tensile properties of single osteons. Ana Rec 158:375–386Barbour KE, Zmuda JM, Strotmeyer ES, Horwitz MJ, Boudreau R, Evans RW, Ensrud K, Petit MA, Gordon CL, Cauley JA (2013) Correlates of trabecular and cortical volumetric bone mineral density of the radius and tibia older men: the osteoporotic fractures in men study. 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Academic Press, New York, pp 289–300Jäger I, Fratzl P (2000) Mineralized collagen: a mechanical model with a staggered arrangement of mineral particles. Biophys J 78:1737–1746Kuhn JL, Goldstein SA, Choi K, London M, Feldkamp LA, Matthews LS (1989) Comparison of the trabecular and cortical tissue moduli from human iliac crests. J Orthop Res 7:876–884Landis WJ, Song MJ, Leith A, McEwen L, McEwen BF (1993) Mineral and organic matrix interaction in normally calcifying tendon visualized in three dimensions by high-voltage electron microscopic tomography and graphic image reconstruction. J Struct Biol 110:39–54Lees S, Heeley JD, Cleary PF (1979) A study of some properties of a sample of bovine cortical bone using ultrasound. Calcif Tissue Int 29:107–117Lekhnitskii SG (1963) Theory of elasticity of anisotropic elastic body. Holden-Day, San Francisco, pp 1–73Lempriere BM (1968) Poisson’s ratio in orthotropic materials. Am Inst Aeronaut Astronaut J J6:2226–2227Liu Y, Kim YK, Dai L, Li N, Khan SO, Pashley DH, Tay FR (2011) Hierarchical and non-hierarchical mineralization of collagen. Biomater 32:1291–1300Majumdar S, Kothari M, Augat P, Newitt DC, Link TM, Lin JC, Lang T, Lu Y, Genant HK (1998) High-resolution magnetic resonance imaging: three-dimensional trabecular bone architecture and biomechanical properties. Bone 22(5):445–454Martínez-Reina J, Domínguez J, García-Aznar JM (2011) Effect of porosity and mineral content on the elastic constants of cortical bone: a multiscale approach. Biomech Model Mechanobiol 10:309–322Nobakhti S, Limbert G, Thurner PJ (2014) Cement lines and interlamellar areas in compact bone as strain amplifiers—Contributors to elasticity, fracture toughness and mechanotransduction. J Mech Behav Biomed Mater 29:235–251Orgel JPRO, Irving TC, Miller A, Wess TJ (2006) Microfibrillar structure of type I collagen in situ. PNAS USA 103:9001–9005Reisinger AG, Pahr DH, Zysset PK (2010) Sensitivity analysis and parametric study of elastic properties of unidirectional mineralized bone fibril-array using mean field methods. Biomech Model Mechanobiol 9:499–510Reisinger AG, Pahr DH, Zysset PK (2011) Elastic anisotropy of bone lamellae as a function of fibril orientation pattern. Biomech Model Mechanobiol 10:67–77Rho JY, Kuhn-Spearing L, Zioupos P (1998) Mechanical properties and the hierarchical structure of bone. Med Eng Phys 20:92–102Robinson RA, Rochester MD (1952) An electron-microscopic study of the crystalline inorganic component of bone and its relationship to the organic matrix. J Bone Joint Surg 34–a:389–435Roque WL, Arcaro K, Alberich-Bayarri A (2013) Mechanical competence of bone: a new parameter to grade trabecular bone fragility from tortuosity and elasticity. 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Prospective evaluation of the impact of sonography on the management and surgical intervention of neonates with necrotizing enterocolitis

Background/aimEstablished indications for surgery in necrotizing enterocolitis (NEC) are pneumoperitoneum and failure to improve or clinical deterioration with medical treatment alone. It has been proposed that infants with intestinal necrosis may benefit from surgery in the absence of one of these indications yet the diagnosis of definitive intestinal necrosis is challenging. Recent data suggest that abdominal ultrasound (US) examination focused on the gastrointestinal tract and the peritoneal cavity may be of utility in this regard. The aim of this study was to evaluate the ability of abdominal US to detect intestinal necrosis in infants with radiographically confirmed NEC.MethodsTwenty-six consecutive infants with Bell stage II or III NEC were prospectively included in the study between September 2013 and July 2014. Infants with a pre-existing indication for surgery were excluded. At least one abdominal US examination was performed in each patient using a standardized previously described method. Surgery was performed at the discretion of the attending surgeon based on clinical and imaging findings. Clinical, radiographic, US, and intra-operative data were recorded to allow comparison between US findings, surgical findings and outcome.ResultsUS demonstrated signs of intestinal necrosis in 5 of the 26 patients. All of these five had laparotomy. Intestinal necrosis requiring resection was confirmed in four and the other was found to have NEC but no necrosis was identified. In 21 patients US did not suggest intestinal necrosis. Of these, only one had surgery in whom NEC but no necrosis was identified. The remaining 20 responded to medical treatment for NEC and were assumed not to have had intestinal necrosis based on improvement without surgical intervention. The sensitivity, specificity, positive predictive value and negative predictive values of US for the detection of bowel necrosis were calculated as 100, 95.4, 80.0, and 100 %, respectively.ConclusionOur prospective findings suggest that abdominal US can identify those infants with NEC who may need surgery by detecting bowel necrosis (prior to the development of perforation or medical deterioration) with high sensitivity and specificity. Early surgical intervention in the clinical pathway of NEC may lead to improved outcomes