Use Of The Vascularized Iliac-crest Flap In Musculoskeletal Lesions.

Bone loss was in the past treated by several methods, such as bone distraction and the use of nonvascularized or tissue-bank bone grafts. With the advent of modern microsurgical techniques, the vascularized bone flap has been used with good results; it resolves local nutritional problems, repairs soft tissue that is often damaged by severe trauma, and treats bone loss due to tumors, pseudarthroses, and osteomyelitis. This paper reports the authors' experience with the use of vascularized iliac-crest flaps to treat orthopedic pathologies in five patients with traumatic bone loss (<10 cm), three with osteomyelitis, and three with atrophic nonunion. In all cases, the same surgeon obtained a vascularized iliac-crest flap with a pedicle based on the deep iliac circumflex artery. All flaps consolidated within a mean period of 3 months. These findings demonstrate that the use of an iliac-crest flap is a treatment option in cases of bone loss and that it is associated with good functional results and minimal donor-site morbidity.201323714

Feedforward and Modal Control for a Multi Degree of Freedom High Precision Machine

High precision industrial machines suffer the presence of vibrations due to several noise sources: ground vibration, acoustic noise, direct force disturbances. In the last years the need of higher processing quality and throughput result in a continuing demand for higher accuracy. Therefore vibration isolation systems became mandatory to satisfy these requests. In general, machine supports are designed for high stiffness to obtain a robust machine alignment with respect to its surroundings. However, in the presence of significant ground vibration levels the support stiffness is commonly sacrificed to reduce their transmission to the payload stage. Efforts to go towards these issues are recorded in several applications and the solutions are different for any particular situation, depending on the nature of the vibration sources, the amount of the disturbances and the machine environment. This chapter focuses on the evaluation of a vibration isolation device on the working cell of a micro-mechanical laser center, using active electromagnetic actuators. The machine is composed by two main parts: a frame support and a payload stage where the laser cutting is performed. The machine potential in terms of accuracy and precision is reduced by the presence of two main vibration sources: the ground and the stage itself. The active device should meet two main goals: the payload vibrations damping and the reduction of the transmissibility of ground disturbances. In this work the phases followed to design, realize and validate the device are illustrated with a particular attention to the mechatronics aspects of the project and to the control strategies. The chapter starts on the description of the common solutions and of the techniques described in literature. The requirements analysis and a trade-off phase on the available opportunities for vibration isolation are described. An analysis of the plant components is reported in the second section along with an exhaustive explanation of a) actuation subsystem consisting in four voice-coils, two per axis; b) sensing subsystem aimed to measure the absolute velocities of the frame support and of the stage are measured by means of eight geophone sensors. The considerations leading to the choice of this sensing system are reported along with the signal conditioning block. The active control is performed with a digital platform based on DSP and FPGA. The core of the chapter is the description of the modeling approach and of the control strategies design. The bond-graph approach is used to represent the system behavior, in particular the interactions between the mechanical and electrical subsystems are illustrated. The realized model includes the plant, the sensing, the control and the actuation blocks. The plant is considered as a classical two mass-spring-damper system resulting on a multi-input multi-output system (MIMO), considering disturbances from the stage and the ground and the actuators action between the two masses. Time and frequency domain computations are carried out from the model to evaluate vibration levels and displacements and to identify which parameters need to be carefully designed to satisfy the requirements. The control strategy is focused on the attenuation of the effects of microvibrations on the stage caused by different sources. The technique consists in a combination of two actions, the goal being the minimization of the ground vibrations transmission and the payload vibrations damping: • A single-axis decentralized action consisting in a modal controller used to compensate the high-pass band dynamic of the geophone sensors and to control the vibrations. • A feedforward action working on the disturbances coming from the payload and from the ground. This control is not generated in on-line, but computed in advance from the data of machine responses to the direct disturbances coming from the floor and the stage and resulting in vibrations on the payload and on the frame. The first action itself is aimed to perform active isolation and vibration that nevertheless could be not sufficient for severe specifications applications. The feedforward action is hence used to face this shortcoming by suppressing direct disturbance. The controller design phases along with its performance evaluation are described. The chapter concludes on the illustration of the results obtained with the proposed modeling and control strategy

Proteomic profiling reveals the transglutaminase-2 externalization pathway in kidneys after unilateral ureteric obstruction

Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD

Open mirror symmetry for Pfaffian Calabi-Yau 3-folds

We investigate the open mirror symmetry of certain non-complete intersection Calabi- Yau 3-folds, so called pfaffian Calabi-Yau. We perform the prediction of the number of disk invariants of several examples by using the direct integration method proposed recently and the open mirror symmetry. We treat several pfaffian Calabi-Yau 3-folds in $\mathbb{P}^6$ and branes with two discrete vacua. Some models have the two special points in its moduli space, around both of which we can consider different A-model mirror partners. We compute disc invariants for both cases. This study is the first application of the open mirror symmetry to the compact non-complete intersections in toric variety.Comment: 64 pages; v2: typos corrected, minor changes, references added; v3: published version, minor corrections and improvement

Effects of Eucalyptus pulp refining on the performance and durability of fibre-cement composites

Although Eucalyptus pulp has been widely used in the paper industry, there is limited information concerning its use as reinforcement in fibre-cement composites. The objective of this study was to evaluate effects of mechanical treatment (refining) of the Eucalyptus pulp on fibre properties as well as performance and microstructure of fibre-cement composites. The composites were evaluated before and after accelerated ageing cycles. The refining increased the capacity of Eucalyptus fibres to capture mineral particles, improving the adherence of the fibres with the matrix. This improved fibre-matrix interface led to better mechanical properties at 28 days of cure but higher mineralisation of fibres and consequently increased brittleness of composites after accelerated ageing (soak and dry) cycles. Unrefined fibres maintained the toughness of composites after ageing cycles. This indicates that refining may weaken the fibres thus affecting the mechanical performance (mainly decreasing modulus of rupture and toughness) of composites after ageing cycles. These results are useful for understanding effects of refined fibre conditions (morphology, mechanical strength and surface properties) on mechanisms of fibre-matrix adherence, fibre mineralisation and degradation of fibre-cement composites.FAPESP (05/59072-4, 07/05299-3)FAPEMIGCAPESCNP

Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers.

The transcription factor Sox2 is essential for neural stem cells (NSC) maintenance in the hippocampus and in vitro. The transcription factor Emx2 is also critical for hippocampal development and NSC self-renewal. Searching for 'modifier' genes affecting the Sox2 deficiency phenotype in mouse, we observed that loss of one Emx2 allele substantially increased the telencephalic β-geo (LacZ) expression of a transgene driven by the 5' or 3' Sox2 enhancer. Reciprocally, Emx2 overexpression in NSC cultures inhibited the activity of the same transgene. In vivo, loss of one Emx2 allele increased Sox2 levels in the medial telencephalic wall, including the hippocampal primordium. In hypomorphic Sox2 mutants, retaining a single 'weak' Sox2 allele, Emx2 deficiency substantially rescued hippocampal radial glia stem cells and neurogenesis, indicating that Emx2 functionally interacts with Sox2 at the stem cell level. Electrophoresis mobility shift assays and transfection indicated that Emx2 represses the activities of both Sox2 enhancers. Emx2 bound to overlapping Emx2/POU-binding sites, preventing binding of the POU transcriptional activator Brn2. Additionally, Emx2 directly interacted with Brn2 without binding to DNA. These data imply that Emx2 may perform part of its functions by negatively modulating Sox2 in specific brain areas, thus controlling important aspects of NSC function in development

Therapeutical innovations and medical responsibility: What's new in oto-laryngology

On one hand the incessant and constant technological and instrumental progress in the medical fieldhas allowed to increase knowledge and to reach new objectives. On the other hand, however, it has also raised the risk linked to professional responsibility, regarding informed consent and law 24/2017 of the Italian Republic, better known as Gelli Bianco. In this work an analysis of relevant literature will be presented, followed by a study on the role of new devices on responsibility profiles in otolaryngology. According to the analysis of the Italian law and considering the weaknesses ofthe above mentioned guidelines, pending legal administrative clarifications, we believe an operational protocol can be proposed in case of application of therapeutical innovations, especially about experimental introductions. Consequently, in our opinion, the risk of incrimination persists in case of use of innovative procedures in the absence of a formal shared opinion expressed in guidelines or in good practices, which still need a satisfactory definition

Steering Away from Current Amoxicillin Dose Reductions in Hospitalized Patients with Impaired Kidney Function to Avoid Subtherapeutic Drug Exposure.

Current dose reductions recommended for amoxicillin in patients with impaired kidney function could lead to suboptimal treatments. In a prospective, observational study in hospitalized adults with varying kidney function treated with an IV or oral dose of amoxicillin, amoxicillin concentrations were measured in 1-2 samples on the second day of treatment. Pharmacometric modelling and simulations were performed to evaluate the probability of target attainment (PTA) for 40% of the time above MIC following standard (1000 mg q6h), reduced or increased IV dosing strategies. A total of 210 amoxicillin samples was collected from 155 patients with kidney function based on a CKD-EPI of between 12 and 165 mL/min/1.73 m2. Amoxicillin clearance could be well predicted with body weight and CKD-EPI. Recommended dose adjustments resulted in a clinically relevant reduction in the PTA for the nonspecies-related PK/PD breakpoint MIC of 8 mg/L (92%, 62% and 38% with a CKD-EPI of 10, 20 and 30 mL/min/1.73 m2, respectively, versus 100% for the standard dose). For MICs ≤ 2 mg/L, PTA &gt; 90% was reached in these patients following both reduced and standard dose regimens. Our study showed that for amoxicillin, recommended dose reductions with impaired kidney function could lead to subtherapeutic amoxicillin concentrations in hospitalized patients, especially when targeting less susceptible pathogens