Obesity due to Melanocortin 4 Receptor (MC4R) Deficiency Is Associated with Increased Linear Growth and Final Height, Fasting Hyperinsulinemia, and Incompletely Suppressed Growth Hormone Secretion

Context: Melanocortin receptor 4 (MC4R) deficiency is characterized by increased linear growth greater than expected for the degree of obesity. Objective: The objective of the investigation was to study the somatotroph axis in obese MC4R-deficient patients and equally obese controls. Patients and Methods: We obtained anthropometric measurements and insulin concentrations in 153 MC4R-deficient subjects and 1392 controls matched for age and severity of obesity. We measured fasting IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit levels in a subset of 33 MC4R-deficient patients and 36 control subjects. We examined pulsatile GH secretion in six adult MC4R-deficient subjects and six obese controls. Results: Height so score was significantly greater in MC4R-deficient children under 5 yr of age compared with controls (mean +/- SEM: 2.3 +/- 0.06 vs. 1.8 +/- 0.04, P < 0.001), an effect that persisted throughout childhood. Final height (cm) was greater in MC4R-deficient men (mean +/- SEM 173 +/- 2.5 vs. 168 +/- 2.1, P < 0.001) and women (mean 165 +/- 2.1 vs. 158 +/- 1.9, P < 0.001). Fasting IGF-I, IGF-II, acid-labile subunit, and IGFBP-3 concentrations were similar in the two groups. GH levels were markedly suppressed in obese controls, but pulsatile GH secretion was retained in MC4R deficiency. The mean maximal GH secretion rate per burst (P < 0.05) and mass per burst (P < 0.05) were increased in MC4R deficiency, consistent with increased pulsatile and total GH secretion. Fasting insulin levels were markedly elevated in MC4R-deficient children. Conclusions: In MC4R deficiency, increased linear growth in childhood leads to increased adult final height, greater than predicted by obesity alone. GH pulsatility is maintained in MC4R deficiency, a finding consistent with animal studies, suggesting a role for MC4R in controlling hypothalamic somatostatinergic tone. Fasting insulin levels are significantly higher in children carrying MC4R mutations. Both of these factors may contribute to the accelerated growth phenotype characteristic of MC4R deficiency. (J Clin Endocrinol Metab 96: E181-E188, 2011)

Focal and linear endocardial and epicardial catheter-based cryoablation of normal and infarcted ventricular tissue

Background: This study of a chronic porcine postinfarction model examined whether linear epicardial cryoablation was capable of creating large, homogenous lesions in regions of the myocardium including scarred ventricle. Endocardial and epicardial focal cryolesions were also compared to determine if there were significant differences in lesion characteristics. Methods: Eighty focal endocardial and 28 focal epicardial cryoapplications were delivered to eight normal caprine and four normal porcine ventricular myocardium, and 21 linear cryolesions were applied along the border of infarcted epicardial tissue in a chronic porcine infarct model in six swines. Results: Focal endocardial cryolesions in normal animals measured 9.7 +/- 0.4 mm (length) by 7.3 +/- 1.4 mm (width) by 4.8 +/- 0.2 mm (depth), while epicardial lesions measured 10.2 +/- 1.4 mm (length) by 7.7 +/- 2 mm (width) by 4.6 +/- 0.9 mm (depth); P > 0.05. Linear epicardial cryolesions in the chronic porcine infarct model measured 36.5 +/- 7.8 mm (length) by 8.2 +/- 1.3 mm (width) by 6.0 +/- 1.2 mm (depth). The mean depth of linear cryolesions applied to the border of the infarct scar was 7 +/- 0.7 mm, as measured by magnetic resonance imaging. Conclusions:Cryoablation can create deep lesions when delivered to the ventricular epicardium. Endocardial and epicardial cryolesions created by a focal cryoablation catheter are similar in size and depth. The ability to rapidly create deep linear cryolesions may prove to be beneficial in substrate-based catheter ablation of ventricular arrhythmias.

Assessment of linear measurements of bone for implant sites in the presence of metallic artefacts using cone beam computed tomography and multislice computed tomography

The objective was to evaluate the influence of dental metallic artefacts on implant sites using multislice and cone-beam computed tomography techniques. Ten dried human mandibles were scanned twice by each technique, with and without dental metallic artefacts. Metallic restorations were placed at the top of the alveolar ridge adjacent to the mental foramen region for the second scanning. Linear measurements (thickness and height) for each cross-section were performed by a single examiner using computer software. All mandibles were analysed at both the right and the left mental foramen regions. For the multislice technique, dental metallic artefact produced an increase of 5% in bone thickness and a reduction of 6% in bone height; no significant differences (p > 0.05) were detected when comparing measurements performed with and without metallic artefacts. With respect to the cone-beam technique, dental metallic artefact produced an increase of 6% in bone thickness and a reduction of 0.68% in bone height. No significant differences (p > 0.05) were observed when comparing measurements performed with and without metallic artefacts. The presence of dental metallic artefacts did not alter the linear measurements obtained with both techniques, although its presence made the location of the alveolar bone crest more difficult.

Assessment of linear and angular measurements on three-dimensional cone-beam computed tomographic images

Objective. The purpose of this research was to provide further evidence to demonstrate the precision and accuracy of maxillofacial linear and angular measurements obtained by cone-beam computed tomography (CBCT) images. Study design. The study population consisted of 15 dry human skulls that were submitted to CBCT, and 3-dimensional (3D) images were generated. Linear and angular measurements based on conventional craniometric anatomical landmarks, and were identified in 3D-CBCT images by 2 radiologists twice each independently. Subsequently, physical measurements were made by a third examiner using a digital caliper and a digital goniometer. Results. The results demonstrated no statistically significant difference between inter-and intra-examiner analysis. Regarding accuracy test, no statistically significant differences were found of the comparison between the physical and CBCT-based linear and angular measurements for both examiners (P = .968 and .915, P = .844 and .700, respectively). Conclusions. 3D-CBCT images can be used to obtain dimensionally accurate linear and angular measurements from bony maxillofacial structures and landmarks. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: 430-436)

Influence of interimplant distances and placement depth on peri-implant bone remodeling of adjacent and immediately loaded Morse cone connection implants: a histomorphometric study in dogs

Objectives The aim of this study was to histomorphometrically evaluate the influence of interimplant distances (ID) and implant placement depth on bone remodeling around contiguous Morse cone connection implants with `platform-shifting` in a dog model. Material and methods Bilateral mandibular premolars of six dogs were extracted, and after 12 weeks, each dog received 8 implants, four placed 1.5 mm subcrestally (SCL) on one side of the mandible and four placed equicrestally (ECL) on the other side, alternating the ID of 2 and 3 mm. The experimental groups were SCL with IDs of 2 mm (2 SCL) and 3 mm (3 SCL) and ECL with IDs of 2 mm (2 ECL) and 3 mm (3 ECL). Metallic crowns were immediately installed. After 8 weeks, the animals were euthanized and histomorphometric analyses were performed to compare bone remodeling in the groups. Results The SCL groups` indices of crestal bone resorption were significantly lower than those of ECL groups. In addition, the vertical bone resorption around the implants was also numerically inferior in the SCL groups, but without statistical significance. No differences were obtained between the different IDs. All the groups presented similar good levels of bone-to-implant contact and histological bone density. Conclusion The subcrestal placement of contiguous Morse cone connection implants with `platform shifting` was more efficient in preserving the interimplant crestal bone. The IDs of 2 and 3 mm did not affect the bone remodeling significantly under the present conditions. To cite this article:Barros RRM, Novaes AB Jr., Muglia VA, Iezzi G, Piattelli A. Influence of interimplant distances and placement depth on peri-implant bone remodeling of adjacent and immediately loaded Morse cone connection implants: a histomorphometric study in dogs.Clin. Oral Impl. Res. 21, 2010; 371-378.doi: 10.1111/j.1600-0501.2009.01860.x.

Effect of repeated torque/mechanical loading cycles on two different abutment types in implants with internal tapered connections: an in vitro study

Internal tapered connections were developed to improve biomechanical properties and to reduce mechanical problems found in other implant connection systems. The purpose of this study was to evaluate the effects of mechanical loading and repeated insertion/removal cycles on the torque loss of abutments with internal tapered connections. Sixty-eight conical implants and 68 abutments of two types were used. They were divided into four groups: groups 1 and 3 received solid abutments, and groups 2 and 4 received two-piece abutments. In groups 1 and 2, abutments were simply installed and uninstalled; torque-in and torque-out values were measured. In groups 3 and 4, abutments were installed, mechanically loaded and uninstalled; torque-in and torque-out values were measured. Under mechanical loading, two-piece abutments were frictionally locked into the implant; thus, data of group 4 were catalogued under two subgroups (4a: torque-out value necessary to loosen the fixation screw; 4b: torque-out value necessary to remove the abutment from the implant). Ten insertion/removal cycles were performed for every implant/abutment assembly. Data were analyzed with a mixed linear model (P <= 0.05). Torque loss was higher in groups 4a and 2 (over 30% loss), followed by group 1 (10.5% loss), group 3 (5.4% loss) and group 4b (39% torque gain). All the results were significantly different. As the number of insertion/removal cycles increased, removal torques tended to be lower. It was concluded that mechanical loading increased removal torque of loaded abutments in comparison with unloaded abutments, and removal torque values tended to decrease as the number of insertion/removal cycles increased. To cite this article:Ricciardi Coppede A, de Mattos MdaGC, Rodrigues RCS, Ribeiro RF. Effect of repeated torque/mechanical loading cycles on two different abutment types in implants with internal tapered connections: an in vitro study.Clin. Oral Impl. Res. 20, 2009; 624-632.doi: 10.1111/j.1600-0501.2008.01690.x.

Fracture Resistance of the Implant-Abutment Connection in Implants with Internal Hex and Internal Conical Connections Under Oblique Compressive Loading: An In Vitro Study

The objective of this study was to verify if differences in the design of internal hex (IH) and internal conical (IC) connection implant systems influence fracture resistance under oblique compressive forces. Twenty implant-abutment assemblies were utilized: 10 with IH connections and 10 with IC connections. Maximum deformation force for IC implants (90.58 +/- 6.72 kgf) was statistically higher than that for IH implants (83.73 +/- 4.94 kgf) (P = .0182). Fracture force for the IH implants was 79.86 +/- 4.77 kgf. None of the IC implants fractured. The friction-locking mechanics and the solid design of the IC abutments provided greater resistance to deformation and fracture under oblique compressive loading when compared to the IH abutments. Int J Prosthodont 2009;22:283-286.

Bone Remodeling Adjacent to Morse Cone-Connection Implants with Platform Switch: A Fluorescence Study in the Dog Mandible

Purpose: The aim of this study was to evaluate, through fluorescence analysis, the effect that different interimplant distances, after prosthetic restoration, will have on bone remodeling in submerged and nonsubmerged implants restored with a ""platform switch."" Materials and Methods: Fifty-six Ankylos implants were placed 1.5 mm subcrestally in seven dogs. The implants were placed so that two fixed prostheses, with three interimplant contacts separated by 1-mm, 2-mm, and 3-mm distances, could be fabricated for each side of the mandible. The sides and the positions of the groups were selected randomly. To better evaluate bone remodeling, calcein green was injected 3 days before placement of the prostheses at 12 weeks postimplantation. At 3 days before sacrifice (8 weeks postloading), alizarin red was injected. The amounts of remodeled bone within the different interimplant areas were compared statistically before and after loading in submerged and nonsubmerged implants. Results: Statistically significant differences existed in the percentage of remodeled bone seen in the different regions. Mean percentages of remodeled bone in the submerged and nonsubmerged groups, respectively, were as follows: for the 1-mm distance, 23.0% +/- 0.05% and 23.1% +/- 0.03% preloading and 27.0% +/- 0.03% and 25.2% +/- 0.04% postloading, for the 2-mm distance, 18.2% +/- 0.05% and 18.1% +/- 0.04% preloading and 21.3% +/- 0.07% and 19.9% +/- 0.03% postloading, for the 3-mm distance, 18.3% +/- 0.03% and 18.3% +/- 0.03% preloading and 18.8% +/- 0.04% and 19.8% +/- 0.04% postloading, for distal-extension regions, 16.6% +/- 0.02% and 17.4% +/- 0.04% preloading and 17.0% +/- 0.04% and 18.4% +/- 0.04% postloading. Conclusions: Based upon this animal study, loading increases bone formation for submerged or nonsubmerged implants, and the interimplant distance of 1 mm appears to result in more pronounced bone remodeling than the 2-mm or 3-mm distances in implants with a ""platform switch."" INT J ORAL MAXILLOFAC IMPLANTS 2009;24:257-266

Comparing performance of instrumental drift correction by linear and quadratic adjusting in inductive electromagnetic data

Electromagnetic induction (EMI) method results are shown for vertical magnetic dipole (VMD) configuration by using the EM38 equipment. Performance in the location of metallic pipes and electrical cables is compared as a function of instrumental drift correction by linear and quadratic adjusting under controlled conditions. Metallic pipes and electrical cables are buried at the IAG/USP shallow geophysical test site in Sao Paulo City. Brazil. Results show that apparent electrical conductivity and magnetic susceptibility data were affected by ambient temperature variation. In order to obtain better contrast between background and metallic targets it was necessary to correct the drift. This correction was accomplished by using linear and quadratic relation between conductivity/susceptibility and temperature intending comparative studies. The correction of temperature drift by using a quadratic relation was effective, showing that all metallic targets were located as well deeper targets were also improved. (C) 2010 Elsevier B.V. All rights reserved.

COMPARISON BETWEEN LINEAR AND DAILY UNDULATING PERIODIZED RESISTANCE TRAINING TO INCREASE STRENGTH

Prestes, J, Frollini, AB, De Lima, C, Donatto, FF, Foschini, D, de Marqueti, RC, Figueira Jr, A, and Fleck, SJ. Comparison between linear and daily undulating periodized resistance training to increase strength. J Strength Cond Res 23(9): 2437-2442, 2009-To determine the most effective periodization model for strength and hypertrophy is an important step for strength and conditioning professionals. The aim of this study was to compare the effects of linear (LP) and daily undulating periodized (DUP) resistance training on body composition and maximal strength levels. Forty men aged 21.5 +/- 8.3 and with a minimum 1-year strength training experience were assigned to an LP (n = 20) or DUP group (n = 20). Subjects were tested for maximal strength in bench press, leg press 45 degrees, and arm curl (1 repetition maximum [RM]) at baseline (T1), after 8 weeks (T2), and after 12 weeks of training (T3). Increases of 18.2 and 25.08% in bench press 1 RM were observed for LP and DUP groups in T3 compared with T1, respectively (p <= 0.05). In leg press 45 degrees, LP group exhibited an increase of 24.71% and DUP of 40.61% at T3 compared with T1. Additionally, DUP showed an increase of 12.23% at T2 compared with T1 and 25.48% at T3 compared with T2. For the arm curl exercise, LP group increased 14.15% and DUP 23.53% at T3 when compared with T1. An increase of 20% was also found at T2 when compared with T1, for DUP. Although the DUP group increased strength the most in all exercises, no statistical differences were found between groups. In conclusion, undulating periodized strength training induced higher increases in maximal strength than the linear model in strength-trained men. For maximizing strength increases, daily intensity and volume variations were more effective than weekly variations.

Exact Search Directions for Optimization of Linear and Nonlinear Models Based on Generalized Orthonormal Functions

A novel technique for selecting the poles of orthonormal basis functions (OBF) in Volterra models of any order is presented. It is well-known that the usual large number of parameters required to describe the Volterra kernels can be significantly reduced by representing each kernel using an appropriate basis of orthonormal functions. Such a representation results in the so-called OBF Volterra model, which has a Wiener structure consisting of a linear dynamic generated by the orthonormal basis followed by a nonlinear static mapping given by the Volterra polynomial series. Aiming at optimizing the poles that fully parameterize the orthonormal bases, the exact gradients of the outputs of the orthonormal filters with respect to their poles are computed analytically by using a back-propagation-through-time technique. The expressions relative to the Kautz basis and to generalized orthonormal bases of functions (GOBF) are addressed; the ones related to the Laguerre basis follow straightforwardly as a particular case. The main innovation here is that the dynamic nature of the OBF filters is fully considered in the gradient computations. These gradients provide exact search directions for optimizing the poles of a given orthonormal basis. Such search directions can, in turn, be used as part of an optimization procedure to locate the minimum of a cost-function that takes into account the error of estimation of the system output. The Levenberg-Marquardt algorithm is adopted here as the optimization procedure. Unlike previous related work, the proposed approach relies solely on input-output data measured from the system to be modeled, i.e., no information about the Volterra kernels is required. Examples are presented to illustrate the application of this approach to the modeling of dynamic systems, including a real magnetic levitation system with nonlinear oscillatory behavior.

Methods of Estimation in Multiple Linear Regression: Application to Clinical Data

Nesse artigo, tem-se o interesse em avaliar diferentes estratégias de estimação de parâmetros para um modelo de regressão linear múltipla. Para a estimação dos parâmetros do modelo foram utilizados dados de um ensaio clínico em que o interesse foi verificar se o ensaio mecânico da propriedade de força máxima (EM-FM) está associada com a massa femoral, com o diâmetro femoral e com o grupo experimental de ratas ovariectomizadas da raça Rattus norvegicus albinus, variedade Wistar. Para a estimação dos parâmetros do modelo serão comparadas três metodologias: a metodologia clássica, baseada no método dos mínimos quadrados; a metodologia Bayesiana, baseada no teorema de Bayes; e o método Bootstrap, baseado em processos de reamostragem.

Black-box decomposition approach for computational hemodynamics: One-dimensional models

Increasing efforts exist in integrating different levels of detail in models of the cardiovascular system. For instance, one-dimensional representations are employed to model the systemic circulation. In this context, effective and black-box-type decomposition strategies for one-dimensional networks are needed, so as to: (i) employ domain decomposition strategies for large systemic models (1D-1D coupling) and (ii) provide the conceptual basis for dimensionally-heterogeneous representations (1D-3D coupling, among various possibilities). The strategy proposed in this article works for both of these two scenarios, though the several applications shown to illustrate its performance focus on the 1D-1D coupling case. A one-dimensional network is decomposed in such a way that each coupling point connects two (and not more) of the sub-networks. At each of the M connection points two unknowns are defined: the flow rate and pressure. These 2M unknowns are determined by 2M equations, since each sub-network provides one (non-linear) equation per coupling point. It is shown how to build the 2M x 2M non-linear system with arbitrary and independent choice of boundary conditions for each of the sub-networks. The idea is then to solve this non-linear system until convergence, which guarantees strong coupling of the complete network. In other words, if the non-linear solver converges at each time step, the solution coincides with what would be obtained by monolithically modeling the whole network. The decomposition thus imposes no stability restriction on the choice of the time step size. Effective iterative strategies for the non-linear system that preserve the black-box character of the decomposition are then explored. Several variants of matrix-free Broyden`s and Newton-GMRES algorithms are assessed as numerical solvers by comparing their performance on sub-critical wave propagation problems which range from academic test cases to realistic cardiovascular applications. A specific variant of Broyden`s algorithm is identified and recommended on the basis of its computer cost and reliability. (C) 2010 Elsevier B.V. All rights reserved.

Robust linear mixed models with skew-normal independent distributions from a Bayesian perspective

Linear mixed models were developed to handle clustered data and have been a topic of increasing interest in statistics for the past 50 years. Generally. the normality (or symmetry) of the random effects is a common assumption in linear mixed models but it may, sometimes, be unrealistic, obscuring important features of among-subjects variation. In this article, we utilize skew-normal/independent distributions as a tool for robust modeling of linear mixed models under a Bayesian paradigm. The skew-normal/independent distributions is an attractive class of asymmetric heavy-tailed distributions that includes the skew-normal distribution, skew-t, skew-slash and the skew-contaminated normal distributions as special cases, providing an appealing robust alternative to the routine use of symmetric distributions in this type of models. The methods developed are illustrated using a real data set from Framingham cholesterol study. (C) 2009 Elsevier B.V. All rights reserved.

A linear optimization approach to the combined production planning model

Two fundamental processes usually arise in the production planning of many industries. The first one consists of deciding how many final products of each type have to be produced in each period of a planning horizon, the well-known lot sizing problem. The other process consists of cutting raw materials in stock in order to produce smaller parts used in the assembly of final products, the well-studied cutting stock problem. In this paper the decision variables of these two problems are dependent of each other in order to obtain a global optimum solution. Setups that are typically present in lot sizing problems are relaxed together with integer frequencies of cutting patterns in the cutting problem. Therefore, a large scale linear optimizations problem arises, which is exactly solved by a column generated technique. It is worth noting that this new combined problem still takes the trade-off between storage costs (for final products and the parts) and trim losses (in the cutting process). We present some sets of computational tests, analyzed over three different scenarios. These results show that, by combining the problems and using an exact method, it is possible to obtain significant gains when compared to the usual industrial practice, which solve them in sequence. (C) 2010 The Franklin Institute. Published by Elsevier Ltd. All rights reserved.