Antimicrobial therapy for otitis media with effusion ( secretory otitis media)

Objective. —To determine the effectiveness of antimicrobial treatment for otitis media with effusion ( secretory otitis media) in children. Data Source. —We report the reexamination of a previously published study by Mandel et al that evaluated the efficacy of a 2-week course of antimicrobials (amoxicillin trihydrate) with and without a 4-week course of an oral decongestant-antihistamine combination in a double-blind, placebo-controlled, randomized trial involving 518 infants and children with otitis media with effusion. Data Synthesis. —At 4 weeks, amoxicillin efficacy as determined by a tympanometric criterion (P=.121) or by a measure of improvement in hearing (P=.311) was insignificant. Only by otoscopic judgment, which is shown to contain a systematic bias as used in this clinical trial, could an argument be made for a marginal efficacy of amoxicillin at the 4-week end point. Logistic regression analyses of the combined effects of treatment and prognostic factors showed no significant differences between placebo- and antibiotic-treated groups for unilateral effusions and for bilateral effusions. When subjects with unilateral and bilateral effusions were combined, the estimated efficacy of antibiotic treatment was 12.3% by otoscopy (P =.014) and 4.8% by tympanometry (P =.171). We also demonstrate the sensitivity of outcome to diagnostic measures used and provide statistical evidence questioning the validity of otoscopic observations in this study. Six weeks after the termination of amoxicillin therapy, the recurrence of effusion was two to six times higher in the amoxicillin-treated children than in those treated with placebo (P=.001), and resolution of effusion was not significantly different among antibiotic and placebo groups (13.6% and 11.3%, respectively; P=.477). Conclusions. —Amoxicillin with and without decongestant-antihistamine combination is not effective for the treatment of persistent asymptomatic middle-ear effusions in infants and children

Machining strategy development in 5-axis milling operations using process models

Increased productivity and part quality can be achieved by selecting machining strategies and conditions properly. At one extreme very high speed and feed rate with small depth of cut can be used for high productivity whereas deep cuts accompanied with slow speeds and feeds may also provide increased material removal rates in some cases. In this study, it is shown that process models are useful tools to simulate and compare alternative strategies for machining of a part. 5-axis milling of turbine engine compressors made out of titanium alloys is used as the case study where strategies such as flank milling (deep cuts), point milling (light cuts) and stripe milling (medium depths) are compared in terms of process time by considering chatter stability, surface finish and tool deflections

Investigation of lead and tilt angle effects in 5-axis ball-end milling processes

5-axis milling is widely used in aerospace, die-mold and automotive industries, where complex surfaces and geometries are machined. Being special parameters of 5-axis milling, lead and tilt angles have significant effects on the process mechanics and dynamics which have been studied very little up to now. In this paper, first of all, effects of tool tip contact on the surface finish quality is presented, and conditions to avoid tip contact in terms of lead and tilt angles and depth of cut are stated. The effects of lead and tilt angles on cutting forces, torque, form errors and stability are investigated through, modelling and verified by experimental results. It is shown that the cutting geometry, mechanics and dynamics vary drastically and nonlinearly with these angles. For the same material removal rate, forces and stability limits can be quite different for various combinations of lead and tilt angles. The results presented in the paper are expected to help understanding of complex 5-axis milling process mechanics and dynamics in a better way. The results should also help selection of 5-axis milling conditions for higher productivity and machined part quality

Application of AA-PSP to hypersonic flows: the double ramp model

Anodized Aluminium Pressure Sensitive Paint (AA-PSP) is known for its rapid response characteristics, making it a highly desirable technique when studying high-speed phenomenon on a global scale. The current study examines the efficacy of the AA-PSP technique, which is prepared with a more practical approach than that reported in literature, in analysing the flow characteristics of a double ramp model placed in hypersonic flow of M = 5. Three different flow angles of 0°, −2°, and −4° are studied. Two-dimensional colour schlieren visualisation, using a colour wheel, is employed alongside high sensitivity Kulite pressure tap data to corroborate the AA-PSP findings. The AA-PSP results show good correlation between the qualitative schlieren and ±8.9% discrepency with the quantitative pressure tap data. The more practical AA-PSP preparation proposed in the current study, which uses aluminium alloy 6-series rather than pure aluminium, is proved to have the response time and the accuracy to be applied to unsteady high-speed flows

Monte Carlo simulation for statistical mechanics model of ion channel cooperativity in cell membranes

Voltage-gated ion channels are key molecules for the generation and propagation of electrical signals in excitable cell membranes. The voltage-dependent switching of these channels between conducting and nonconducting states is a major factor in controlling the transmembrane voltage. In this study, a statistical mechanics model of these molecules has been discussed on the basis of a two-dimensional spin model. A new Hamiltonian and a new Monte Carlo simulation algorithm are introduced to simulate such a model. It was shown that the results well match the experimental data obtained from batrachotoxin-modified sodium channels in the squid giant axon using the cut-open axon technique.Comment: Paper has been revise

Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans.

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400 mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease

Macrocrystals of Colloidal Quantum Dots in Anthrancene: Exciton Trannsfer and Polarized Emission

Cataloged from PDF version of article.In this work, centimeter-scale macrocrystals of nonpolar colloidal quantum dots (QDs) incorporated into anthracene were grown for the first time. The exciton transfer from the anthracene host to acceptor QDs was systematically investigated, and anisotropic emission from the isotropic QDs in the anthracene macrocrystals was discovered. Results showed a decreasing photoluminescence lifetime of the donor anthracene, indicating a strengthening energy transfer with increasing QD concentration in the macrocrystals. With the anisotropy study, QDs inside the anthracene host acquired a polarization ratio of similar to 1.5 at 0 degrees collection angle, and this increases to similar to 2.5 at the collection angle of 60 degrees. A proof-of-concept application of these excitonic macrocrystals as tunable color converters on light-emitting diodes was also demonstrated

Identification of Predictive Response Markers and Novel Treatment Targets for Gliomas

Gliomas are the most frequent primary brain tumors in adults. Despite multimodality treatment strategies, the survival of patients with a diffuse glioma remains poor. There has been an increasing use of molecular markers to assist diagnosis and predict prognosis and response to therapy. Although several prognostic and predictive response markers have been identified, considerable research still needs to be done to improve on these. Therefore, the identification of novel predictive response markers and therapeutic targets are desperately needed for this dismal disease. In this thesis, we describe prognostic and identify novel predictive markers in randomized clinical trials. We determined the gene expression profiles of samples of anaplastic oligodendrogliomas and oligoastrocytomas from the EORTC 26951 study and samples of recurrent glioblastomas of the BELOB study to evaluate the treatment responses within defined intrinsic glioma subtypes (IGSs). IGSs are molecularly similar tumors that have been previously identified by unsupervised gene expression analysis. We found that IGSs can be used to assess the molecular heterogeneity within clinical trials. In addition, we confirmed that IGS subtypes are prognostic for survival and predictive. Tumors assigned to IGS-9 showed benefit from adjuvant PCV chemotherapy. In the BELOB study, we found that tumors assigned to IGS-18 (classical GBMs) showed a trend towards benefit from Beva+CCNU treatment. Expression of FMO4 and OSBPL3 were particularly associated with treatment response. Intrinsic subtypes can therefore be used to assess the molecular heterogeneity within clinical trials and may be used as a prognostic and predictive marker. Another method to profile gliomas is based on DNA methylation. We performed genome-wide methylation profiling on material from EORTC 26951 and assessed CIMP and MGMT-STP27 status. We have shown that survival in patients with CIMP+ or MGMT-STP27 methylated tumors was improved compared to CIMP- and/or MGMT-STP27 unmethylated tumors. Importantly, the MGMT-STP27 status was predictive for response to adjuvant PCV chemotherapy in these tumors. MGMT-STP27 may therefore be used to identify AODs and AOAs with improved prognosis and identify patients that are likely to benefit from adjuvant PCV chemotherapy. We also performed functional analysis on different mutations on the EGFR gene and infrequently mutated genes in oligodendrogliomas. We have shown that different mutations within a single gene (EGFR) can have different molecular consequences and have different binding partners for EGFRvIII, EGFRL858 and EGFRwildtype. As these mutations have different functions, each mutation may need its own unique treatment. Functional analysis on infrequently mutated genes showed that the function of many of ‘low frequency’ genes, differs from its wildtype counterpart. This differential effect suggests that these genes can contribute to the disease and therefore may offer new therapeutic targets for oligodendrogliomas

Modeling and simulation of 5-axis milling processes

5-axis milling is widely used in machining of complex surfaces. Part quality and productivity are extremely important due to the high cost of machine tools and parts involved. Process models can be used for the selection of proper process parameters. Although extensive research has been conducted on milling process modeling, very few are on 5-axis milling. This paper presents models for 5-axis milling process geometry, cutting force and stability. The application of the models in selection of important parameters is also demonstrated. A practical method, developed for the extraction of cutting geometry, is used in simulation of a complete 5-axis cycle