Tumor bed brachytherapy for locally advanced laryngeal cancer: a feasibility assessment of combination with ferromagnetic hyperthermia

Purpose. To assess the feasibility of adding hyperthermia to an original method of organ-preserving brachytherapy treatment for locally advanced head and neck tumors. Methods and materials. The method involves organ-preserving tumor resection and adjunctive high-dose-rate (HDR) brachytherapy delivered via afterloading catheters. These catheters are embedded in a polymeric implant prepared intraoperatively to fill the resection cavity, allowing precise computer planning of dose distribution in the surrounding at-risk tumor bed tissue. Theoretical and experimental analyzes address the feasibility of heating the tumor bed implant by coupling energy from a 100 kHz magnetic field applied externally into ferromagnetic particles, which are uniformly distributed within the implant. The goal is to combine adjuvant hyperthermia (40 °C–45 °C) to at-risk tissue within 5 mm of the resection cavity for thermal enhancement of radiation and chemotherapy response. Results. A five-year relapse free survival rate of 95.8% was obtained for a select group of 48 male patients with T3N0M0 larynx tumors, when combining organ-preserving surgery with HDR brachytherapy from a tumor bed implant. Anticipating the need for additional treatment in patients with more advanced disease, a theoretical analysis demonstrates the ability to heat at-risk tissue up to 10 mm from the surface of an implant filled with magnetically coupled ferromagnetic balls. Using a laboratory induction heating system, it takes just over 2 min to increase the target tissue temperature by 10 °C using a 19% volume fraction of ferromagnetic spheres in a 2 cm diameter silicone implant. Conclusion. The promising clinical results of a 48 patient pilot study demonstrate the feasibility of a new organ sparing treatment for laryngeal cancer. Anticipating the need for additional therapy, theoretical estimations of potential implant heating are confirmed with laboratory experiments, preparing the way for future implementation of a thermobrachytherapy implant approach for organ-sparing treatment of locally advanced laryngeal cancer

Incidence and diversity of the fungal genera Aspergillus and Penicillium in Portuguese almonds and chestnuts

Almonds (Prunus dulcis (Miller) D.A. Webb) and European (sweet) chestnuts (Castanea sativa Miller) are of great economic and social impact in Mediterranean countries, and in some areas they constitute the main income of rural populations. Despite all efforts to control fungal contamination, toxigenic fungi are ubiquitous in nature and occur regularly in worldwide food supplies, and these nuts are no exception. This work aimed to provide knowledge on the general mycobiota of Portuguese almonds and chestnuts, and its evolution from field to the end of storage. For this matter, 45 field chestnut samples and 36 almond samples (30 field samples and six storage samples) were collected in Trás-os-Montes, Portugal. All fungi belonging to genus Aspergillus were isolated and identified to the section level. Fungi representative of other genera were identified to the genus level. In the field, chestnuts were mainly contaminated with the genera Fusarium, Cladosporium, Alternaria and Penicillium, and the genus Aspergillus was only rarely found, whereas almonds were more contaminated with Aspergillus. In almonds, Aspergillus incidence increased significantly from field to the end of storage, but diversity decreased, with potentially toxigenic isolates belonging to sections Flavi and Nigri becoming more significant and widespread throughout storage. These fungi were determined to be moderately associated, which can be indicative of mycotoxin co-contamination problems if adequate storage conditions are not secured.P. Rodrigues was supported by grants SFRH/BD/28332/2006 from Fundacao para a Ciencia e a Tecnologia (FCT), and SFRH/PROTEC/49555/2009 from FCT and Polytechnic Institute of Braganca, Portugal

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Electric Field-Tuned Topological Phase Transition in Ultra-Thin Na3Bi - Towards a Topological Transistor

The electric field induced quantum phase transition from topological to conventional insulator has been proposed as the basis of a topological field effect transistor [1-4]. In this scheme an electric field can switch 'on' the ballistic flow of charge and spin along dissipationless edges of the two-dimensional (2D) quantum spin Hall insulator [5-9], and when 'off' is a conventional insulator with no conductive channels. Such as topological transistor is promising for low-energy logic circuits [4], which would necessitate electric field-switched materials with conventional and topological bandgaps much greater than room temperature, significantly greater than proposed to date [6-8]. Topological Dirac semimetals(TDS) are promising systems in which to look for topological field-effect switching, as they lie at the boundary between conventional and topological phases [3,10-16]. Here we use scanning probe microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES) to show that mono- and bilayer films of TDS Na3Bi [3,17] are 2D topological insulators with bulk bandgaps >400 meV in the absence of electric field. Upon application of electric field by doping with potassium or by close approach of the STM tip, the bandgap can be completely closed then re-opened with conventional gap greater than 100 meV. The large bandgaps in both the conventional and quantum spin Hall phases, much greater than the thermal energy kT = 25 meV at room temperature, suggest that ultrathin Na3Bi is suitable for room temperature topological transistor operation

Determinants on an efficient cellulase recycling process for the production of bioethanol from recycled paper sludge under high solid loadings

Background: In spite of the continuous efforts and investments in the last decades, lignocellulosic ethanol is still not economically competitive with fossil fuels. Optimization is still required in different parts of the process. Namely, the cost effective usage of enzymes has been pursued by different strategies, one of them being recycling. Results: Cellulase recycling was analyzed on Recycled Paper Sludge (RPS) conversion into bioethanol under intensified conditions. Different cocktails were studied regarding thermostability, hydrolysis efficiency, distribution in the multiphasic system and recovery from solid. Celluclast showed inferior stability at higher temperatures (45-55 ºC), nevertheless its performance at moderate temperatures (40ºC) was slightly superior to other cocktails (ACCELLERASE®1500 and Cellic®CTec2). Celluclast distribution in the solid-liquid medium was also more favorable, enabling to recover 88 % of final activity at the end of the process. A Central Composite Design studied the influence of solids concentration and enzyme dosage on RPS conversion by Celluclast. Solids concentration showed a significant positive effect on glucose production, no major limitations being found from utilizing high amounts of solids under the studied conditions. Increasing enzyme loading from 20 to 30 FPU/ gcellulose had no significant effect on sugars production, suggesting that 22 % solids and 20 FPU/gcellulose are the best operational conditions towards an intensified process. Applying these, a system of multiple rounds of hydrolysis with enzyme recycling was implemented, allowing to maintain steady levels of enzyme activity with only 50 % of enzyme on each recycling stage. Additionally, interesting levels of solid conversion (70-81 %) were also achieved, leading to considerable improvements on glucose and ethanol production comparatively with the reports available so far (3.4 and 3.8 fold, respectively). Conclusions: Enzyme recycling viability depends on enzyme distribution between the solid and liquid phases at the end of hydrolysis, as well as enzymes thermostability. Both are critical features to be observed for a judicious choice of enzyme cocktail. This work demonstrates that enzyme recycling in intensified biomass degradation can be achieved through simple means. The process is possibly much more effective at larger scale, hence novel enzyme formulations favoring this possibility should be developed for industrial usage.This work had the fnancial support of the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/ BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and the MultiBiorefnery project (POCI-01-0145-FEDER-016403). Furthermore, FCT equally supported the Ph.D. grant to DG (SFRH/BD/88623/2012).info:eu-repo/semantics/publishedVersio

Building professional discourse in emerging markets: Language, context and the challenge of sensemaking

Using ethnographic evidence from the former Soviet republics, this article examines a relatively new and mainly unobserved in the International Business (IB) literature phenomenon of communication disengagement that manifests itself in many emerging markets. We link it to the deficiencies of the local professional business discourse rooted in language limitations reflecting lack of experience with the market economy. This hampers cognitive coherence between foreign and local business entities, adding to the liability of foreignness as certain instances of professional experience fail to find adequate linguistic expression, and complicates cross-cultural adjustments causing multi-national companies (MNCs) financial losses. We contribute to the IB literature by examining cross-border semantic sensemaking through a retrospectively constructed observational study. We argue that a relative inadequacy of the national professional idiom is likely to remain a feature of business environment in post-communist economies for some time and therefore should be factored into business strategies of MNCs. Consequently, we recommend including discursive hazards in the risk evaluation of international projects

Silicon strip detectors for two-dimensional soft X-ray imaging at normal incidence

A simple prototype system for static two-dimensional soft X-ray imaging using silicon microstrip detectors irradiated at normal incidence is presented. Radiation sensors consist of single-sided silicon detectors made from 300 mum thick wafers, read by RX64 ASICs. Data acquisition and control is performed by a Windows PC workstation running dedicated LabVIEW routines, connected to the sensors through a PCI-DIO-96 interface. Two-dimensional images are obtained by scanning a lead collimator with a thin slit perpendicular to the strip axis, along the whole detector size; the several strip profiles (slices) taken at each position are then put together to form a planar image. Preliminary results are presented, illustrating the high-resolution imaging capabilities of the system with soft X-rays. (C) 2003 Elsevier B.V. All rights reserved.info:eu-repo/semantics/publishedVersio

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

Study of scattered radiation during fluoroscopy in hip surgery

Objetivo: Medir a intensidade da dose de radiação espalhada em diferentes posições simulando uma intervenção cirúrgica no quadril. Materiais e Métodos: Simulou-se uma intervenção cirúrgica no quadril com apoio da fluoroscopia para estudar a distribuição da radiação espalhada no bloco operatório. Para simular o paciente foi utilizado um simulador antropomórfico de corpo inteiro e para medir a radiação utilizou-se um detector específico para medir raios X. Realizaram-se incidências com um equipamento de raios X tipo arco em C móvel, em modo de escopia contínua, com a ampola a 0° (configuração 1) e a 90° (configuração 2). Os parâmetros operacionais utilizados (voltagem, corrente, tempo de exposição) foram determinados por meio de um estudo estatístico resultante da observação de cirurgias ortopédicas de quadril. Resultados: Em todas as medições observaram-se exposições mais elevadas na configuração 2. Nas medições em função da altura, observaram-se os valores máximos da taxa de dose de 1,167 (± 0,023) µSv/s e 2,278 (± 0,023) µSv/s nas configurações 1 e 2, respectivamente, correspondendo à altura do tórax dos profissionais. No estudo em torno do paciente os valores máximos registraramse na posição ocupada pelo médico cirurgião. Conclusão: Concluiu-se que a exposição à radiação dos profissionais é baixa, podendo ainda ser reduzida mediante o uso de equipamentos de proteção individualObjective: To measure the scattered radiation dose at different positions simulating hip surgery. Materials and Methods: We simulated fluoroscopy-assisted hip surgery in order to study the distribution of scattered radiation in the operating room. To simulate the patient, we used a anthropomorphic whole-body phantom, and we used an X-ray-specific detector to quantify the radiation. Radiographs were obtained with a mobile C-arm X-ray system in continuous scan mode, with the tube at 0° (configuration 1) or 90° (configuration 2). The operating parameters employed (voltage, current, and exposure time) were determined by a statistical analysis based on the observation of orthopedic surgical procedures involving the hip. Results: For all measurements, higher exposures were observed in configuration 2. In the measurements obtained as a function of height, the maximum dose rates observed were 1.167 (± 0.023) µSv/s and 2.278 (± 0.023) µSv/s in configurations 1 and 2, respectively, corresponding to the chest level of health care professionals within the operating room. Proximal to the patient, the maximum values were recorded in the position occupied by the surgeon. Conclusion: We can conclude that, in the scenario under study, health care professionals workers are exposed to low levels of radiation, and that those levels can be reduced through the use of personal protective equipmen

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA