Laser treatment of 13 benign oral vascular lesions by three different surgical techniques

Objectives: Benign Oral Vascular Lesions (BOVLs) are a group of vascular diseases characterized by congenital, inflammatory or neoplastic vascular dilations clinically evidenced as more or less wide masses of commonly dark bluish color. If traumatized BOVLs are characterized by a great risk of hemorrhage and their treatment usually requires great caution to prevent massive bleeding. In the last decades lasers have dramatically changed the way of treatment of BOVLs permitting the application of even peculiar techniques that gave interesting advantages in their management reducing hemorrhage risks. The aim of this study was to evaluate the capabilities and disadvantages of three laser assisted techniques in the management of BOVLs. Study design: In this study 13 BOVLs were treated by three different laser techniques: the traditional excisional biopsy (EB), and two less invasive techniques, the transmucosal thermocoagulation (TMT) and the intralesional photocoagulation (ILP). Two different laser devices were adopted in the study: a KTP laser (DEKA, Florence, Italy, 532nm) and a GaAlAs laser (Laser Innovation, Castelgandolfo, Italy, 808nm) selected since their great effectiveness on hemoglobin. Results: In each case, lasers permitted safe treatments of BOVLs without hemorrhages, both during the intervention and in the post-operative period. The minimally invasive techniques (TMT and ILP) permitted even the safe resolution of big lesions without tissue loss. Conclusions: Laser devices confirm to be the gold standard in BOVLs treatment, permitting even the introduction of minimal invasive surgery principles and reducing the risks of hemorrhage typical of these neoplasms. As usual in laser surgery, it is necessary a clear knowledge of the devices and of the laser-tissue interaction to optimize the results reducing risks and disadvantages

Holography and Variable Cosmological Constant

An effective local quantum field theory with UV and IR cutoffs correlated in accordance with holographic entropy bounds is capable of rendering the cosmological constant (CC) stable against quantum corrections. By setting an IR cutoff to length scales relevant to cosmology, one easily obtains the currently observed rho_Lambda ~ 10^{-47} GeV^4, thus alleviating the CC problem. It is argued that scaling behavior of the CC in these scenarios implies an interaction of the CC with matter sector or a time-dependent gravitational constant, to accommodate the observational data.Comment: 7 pages, final version accepted by PR

Evaluation of resistive-plate-chamber-based TOF-PET applied to in-beam particle therapy monitoring

Particle therapy is a highly conformal radiotherapy technique which reduces the dose deposited to the surrounding normal tissues. In order to fully exploit its advantages, treatment monitoring is necessary to minimize uncertainties related to the dose delivery. Up to now, the only clinically feasible technique for the monitoring of therapeutic irradiation with particle beams is Positron Emission Tomography (PET). In this work we have compared a Resistive Plate Chamber (RPC)-based PET scanner with a scintillation-crystal-based PET scanner for this application. In general, the main advantages of the RPC-PET system are its excellent timing resolution, low cost, and the possibility of building large area systems. We simulated a partial-ring scannerbeam monitoring, which has an intrinsically low positron yield compared to diagnostic PET. In addition, for in-beam PET there is a further data loss due to the partial ring configuration. In order to improve the performance of the RPC-based scanner, an improved version of the RPC detector (modifying the thickness of the gas and glass layers), providing a larger sensitivity, has been simulated and compared with an axially extended version of the crystal-based device. The improved version of the RPC shows better performance than the prototype, but the extended version of the crystal-based PET outperforms all other options. based on an RPC prototype under construction within the Fondazione per Adroterapia Oncologica (TERA). For comparison with the crystal-based PET scanner we have chosen the geometry of a commercially available PET scanner, the Philips Gemini TF. The coincidence time resolution used in the simulations takes into account the current achievable values as well as expected improvements of both technologies. Several scenarios (including patient data) have been simulated to evaluate the performance of different scanners. Initial results have shown that the low sensitivity of the RPC hampers its application to hadro

A minimally invasive, lentiviral based method for the rapid and sustained genetic manipulation of renal tubules.

The accelerated discovery of disease-related genes emerging from genomic studies has strained the capacity of traditional genetically engineered mouse models (GEMMs) to provide in-vivo validation. Direct, somatic, genetic engineering approaches allow for accelerated and flexible genetic manipulation and represent an attractive alternative to GEMMs. In this study we investigated the feasibility, safety and efficiency of a minimally invasive, lentiviral based approach for the sustained in-vivo modification of renal tubular epithelial cells. Using ultrasound guidance, reporter vectors were directly injected into the mouse renal parenchyma. We observed transgene expression confined to the renal cortex (specifically proximal and distal tubules) and sustained beyond 2 months post injection. Furthermore, we demonstrate the ability of this methodology to induce long-term, in-vivo knockdown of candidate genes either through somatic recombination of floxed alleles or by direct delivery of specific shRNA sequences. This study demonstrates that ultrasound-guided injection of lentiviral vectors provides a safe and efficient method for the genetic manipulation of renal tubules, representing a quick and versatile alternative to GEMMs for the functional characterisation of disease-related genes.The authors wish to thank the core facilities (Biological Research Unit, Histopathology, Flow Cytometry and Microscopy) of the CRUK Cambridge Institute for advice and technical assistance. This work was funded by a CRUK Clinician Scientist Fellowship award (C37839/A12177).This is the final version. It was first published by NPG at http://www.nature.com/srep/2015/150605/srep11061/full/srep11061.html

Loss of PBRM1 rescues VHL dependent replication stress to promote renal carcinogenesis

AbstractInactivation of the VHL (Von Hippel Lindau) tumour suppressor has long been recognised as necessary for the pathogenesis of clear cell renal cancer (ccRCC); however, the molecular mechanisms underlying transformation and the requirement for additional genetic hits remain unclear. Here, we show that loss of VHL alone results in DNA replication stress and damage accumulation, effects that constrain cellular growth and transformation. By contrast, concomitant loss of the chromatin remodelling factor PBRM1 (mutated in 40% of ccRCC) rescues VHL-induced replication stress, maintaining cellular fitness and allowing proliferation. In line with these data we demonstrate that combined deletion of Vhl and Pbrm1 in the mouse kidney is sufficient for the development of fully-penetrant, multifocal carcinomas, closely mimicking human ccRCC. Our results illustrate how VHL and PBRM1 co-operate to drive renal transformation and uncover replication stress as an underlying vulnerability of all VHL mutated renal cancers that could be therapeutically exploited.</jats:p

Resummed Quantum Gravity

We present the current status of the a new approach to quantum general relativity based on the exact resummation of its perturbative series as that series was formulated by Feynman. We show that the resummed theory is UV finite and we present some phenomenological applications as well.Comment: 4 pages, 1 figure; presented at ICHEP0

Soft Computing Models for the Development of Commercial Conversational Agents

Proceedings of: 6th International Conference on Soft Computing Models in Industrial and Environmental Applications (SOCO 2011). Salamanca, April 6-8, 2011In this paper we present a proposal for the development of conversational agents that, on the one hand, takes into account the benefits of using standards like VoiceXML, whilst on the other, includes a module with a soft computing model that avoids the effort of manually defining the dialog strategy. This module is trained using a labeled dialog corpus, and selects the next system response considering a classification process based on neural networks that takes into account the dialog history. Thus, system developers only need to define a set of VoiceXML files, each including a system prompt and the associated grammar to recognize the users responses to the prompt. We have applied this technique to develop a conversational agent in VoiceXML that provides railway information in Spanish.Funded by projects CICYT TIN2008-06742-C02-02/TSI, CICYT TEC2008-06732-C02- 02/TEC, CAM CONTEXTS (S2009/TIC-1485), and DPS2008-07029-C02-02.Publicad

Satisfaction with Intrauterine Device Insertion Procedure Among Adolescent and Young Adult Women in a Clinical Trial

OBJECTIVE: To evaluate satisfaction with intrauterine device (IUD) insertion procedures among adolescent and young adult women. METHODS: This secondary analysis of data from a multisite, single-blind, sham-controlled randomized trial of women having a levonorgestrel 13.5-mg IUD inserted enrolled participants from March 2015 through July 2016 at three family planning clinics in Philadelphia, Pennsylvania. Eligible participants were 14-22 years of age, nulliparous, not pregnant, and English-speaking. Randomization was computer-generated allocation in block sizes of four to a 1% lidocaine paracervical or sham block. Only patients were blinded. Satisfaction was measured with three items that assessed overall satisfaction with the procedure, whether participants would recommend the IUD to a friend, and the perception that the IUD was worth the discomfort. Predictors included demographics, sexual and reproductive history, pain after IUD insertion, and treatment group. RESULTS: Ninety-five women enrolled; 93 (97.9%) were included in the analysis. Forty-five (47.4%) were white, 34 (36.0%) were black, 62 (66.0%) were privately insured, and 75 (79.0%) had used contraception previously. Most (n=73 [76.8%]) reported high overall satisfaction with the procedure, 64 (67.4%) would recommend an IUD to a friend, and 79 (83.2%) perceived the IUD was worth the discomfort. The odds of reporting high overall satisfaction were lower among adolescents compared with young adults (odds ratio [OR] 0.07, 95% CI 0.008-0.68); those who never had a gynecologic examination compared with those who had (OR 0.26, 95% CI 0.07-0.99); and decreased as pain score increased (OR 0.96, 95% CI 0.94-0.99). Higher pain scores were negatively correlated with the odds of recommending an IUD to a friend and perceiving the IUD was worth the discomfort. CONCLUSION: Adolescent and young adult women report high levels of satisfaction after the IUD insertion procedure. Young age, lack of experience with gynecologic examinations, and high pain were inversely related to satisfaction

Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits.

In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present study, we generated conditional mutant embryos carrying specific inactivation of Onecut genes in the developing motor neurons, performed RNA-sequencing to identify factors downstream of Onecut proteins in this neuron population, and employed additional transgenic mouse models to assess the role of one specific Onecut-downstream target, the transcription factor Nkx6.2. Nkx6.2 expression was up-regulated in Onecut-deficient motor neurons, but strongly downregulated in Onecut-deficient V2a interneurons, indicating an opposite regulation of Nkx6.2 by Onecut factors in distinct spinal neuron populations. Nkx6.2-null embryos, neonates and adult mice exhibited alterations of locomotor pattern and spinal locomotor network activity, likely resulting from defective survival of a subset of limb-innervating motor neurons and abnormal migration of V2a interneurons. Taken together, our results indicate that Nkx6.2 regulates the development of spinal neuronal populations and the formation of the spinal locomotor circuits downstream of the Onecut transcription factors