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Functionalized monodisperse microbubbles have the potential to boost the sensitivity and efficacy of molecular ultrasound imaging and targeted drug delivery using bubbles and ultrasound. Monodisperse bubbles can be produced in a microfluidic flow focusing device. However, their functionalization and sequential use require removal of the excess lipids from the bubble suspension to minimize the use of expensive ligands and to avoid competitive binding and blocking of the receptor molecules. To date, excess lipid removal is performed by centrifugation, which is labor intensive and challenging to automate. More importantly, as we show, the increased hydrostatic pressure during centrifugation can reduce bubble monodispersity. Here, we introduce a novel automated microfluidic 'washing' method. First, bubbles are injected in a microfluidic chamber 1 mm in height where they are left to float against the top wall. Second, lipid-free medium is pumped through the chamber to remove excess lipids while the bubbles remain located at the top wall. Third, the washed bubbles are resuspended and removed from the device into a collection vial. We demonstrate that the present method can (i) reduce the excess lipid concentration by 4 orders of magnitude, (ii) be fully automated, and (iii) be performed in minutes while the size distribution, functionality, and acoustic response of the bubbles remain unaffected. Thus, the presented method is a gateway to the fully automated production of functionalized monodisperse microbubbles. [ABSTRACT FROM AUTHOR]

Purpose: In arterial disease, the presence of two or more serial stenotic lesions is common. For mild lesions, it is difficult to predict whether their combined effect is hemodynamically significant. This study assessed the hemodynamic significance of idealized serial stenotic lesions by simulating their hemodynamic interaction in a computational flow model. Materials and Methods: Flow was simulated with SimVascular software in 34 serial lesions, using moderate (15 mL/s) and high (30 mL/s) flow rates. Combinations of one concentric and two eccentric lesions, all 50% area reduction, were designed with variations in interstenotic distance and in relative direction of eccentricity. Fluid and fluid–structure simulations were performed to quantify the combined pressure gradient. Results: At a moderate flow rate, the combined pressure gradient of two lesions ranged from 3.8 to 7.7 mmHg, which increased to a range of 12.5–24.3 mmHg for a high flow rate. Eccentricity caused an up to two-fold increase in pressure gradient relative to concentric lesions. At a high flow rate, the combined pressure gradient for serial eccentric lesions often exceeded the sum of the individual lesions. The relative direction of eccentricity altered the pressure gradient by 15–25%. The impact of flow pulsatility and wall deformability was minor. Conclusion: This flow simulation study revealed that lesion eccentricity is an adverse factor in the hemodynamic significance of isolated stenotic lesions and in serial stenotic lesions. Two 50% lesions that are individually non-significant can combine more often than thought to hemodynamic significance in hyperemic conditions. [ABSTRACT FROM AUTHOR]

Background: An International Health Elective (IHE) can be a unique learning experience for students. However, it has proven difficult to clearly define learning outcomes that capture the complexity of an IHE and are aligned with future professional performance. This study aimed to further define learning outcomes for IHEs in low- to middle-income countries (LMIC) from a student perspective. Methods: We conducted a deductive analysis of pre-departure and post-elective reflective reports of fifth-year medical students who participated in an IHE as part of their program. This provided possible learning objectives that were further explored in semi-structured individual interviews with medical students who had recently returned from an IHE. Results: We analyzed 33 reports of students participating in an IHE from 2017–2019 and held 19 interviews. Thematic analysis revealed 9 themes: developing intercultural competence, developing appreciation for differences in health care delivery systems, understanding international health, understanding the global burden of disease, developing a career perspective, developing clinical skills in resource low settings, becoming cost conscious, developing social responsibility and self-actualization. Conclusions: We identified 9 learning outcomes that are directly and indirectly related to clinical practice. They add to the on-going discourse on the benefits of IHEs. These outcomes can be further developed by investigating the perspectives of home and host supervisors and educationalists, while taking the local context into account. Follow-up studies can evaluate to what extend these outcomes are achieve during an IHE. [ABSTRACT FROM AUTHOR]

Purpose: The feasibility of using a compressed interwoven Supera stent as a flow diverting device for popliteal aneurysms was recently demonstrated in patients. It is unclear, however, what the optimal flow diverting strategy is, because of the fusiform shape of popliteal aneurysms and their exposure to triphasic flow. To assess this flow diverting strategy for popliteal aneurysms, flow profiles and thrombus formation likelihood were investigated in popliteal aneurysm models. Materials and Methods: Six popliteal aneurysm models were created and integrated into a pulsatile flow set-up. These models covered a bent and a straight anatomy in three configurations: control, single-lined and dual-lined Supera stents. Two-dimensional flow velocities were visualized by laser particle image velocimetry. In addition, the efficacy of the stent configurations for promoting aneurysm thrombosis was assessed by simulations of residence time and platelet activation. Results: On average for the two anatomies, the Supera stent led to a twofold reduction of velocities in the aneurysm for single-lined stents, and a fourfold reduction for dual-lined stents. Forward flow was optimally diverted, whereas backward flow was generally deflected into the aneurysm. The dual-lined configuration led to residence times of 15–20 s, compared to 5–15 s for the single stent configurations. Platelet activation potential was not increased by the flow diverting stents. Conclusion: A compressed Supera stent was successfully able to divert flow in a popliteal aneurysm phantom. A dual-lined configuration demonstrated superior hemodynamic characteristics compared to its single-lined counterpart. [ABSTRACT FROM AUTHOR]

Background: Two-dimensional (2D) ultrasound is well established for thyroid nodule assessment and treatment guidance. However, it is hampered by a limited field of view and observer variability that may lead to inaccurate nodule classification and treatment. To cope with these limitations, we investigated the use of real-time three-dimensional (3D) ultrasound to improve the accuracy of volume estimation and needle placement during radiofrequency ablation. We assess a new 3D matrix transducer for nodule volume estimation and image-guided radiofrequency ablation. Methods: Thirty thyroid nodule phantoms with thermochromic dye underwent volume estimation and ablation guided by a 2D linear and 3D mechanically-swept array and a 3D matrix transducer. Results: The 3D matrix nodule volume estimations had a lower median difference with the ground truth (0.4 mL) compared to the standard 2D approach (2.2 mL, p < 0.001) and mechanically swept 3D transducer (2.0 mL, p = 0.016). The 3D matrix-guided ablation resulted in a similar nodule ablation coverage when compared to 2D-guidance (76.7% versus 80.8%, p = 0.542). The 3D mechanically swept transducer performed worse (60.1%, p = 0.015). However, 3D matrix and 2D guidance ablations lead to a larger ablated volume outside the nodule than 3D mechanically swept (5.1 mL, 4.2 mL (p = 0.274), 0.5 mL (p < 0.001), respectively). The 3D matrix and mechanically swept approaches were faster with 80 and 72.5 s/mL ablated than 2D with 105.5 s/mL ablated. Conclusions: The 3D matrix transducer estimates volumes more accurately and can facilitate accurate needle placement while reducing procedure time. [ABSTRACT FROM AUTHOR]

Aim: (i) To quantify biofilm removal from a simulated isthmus and a lateral canal in an artificial root canal system during syringe irrigation with NaOCl at different concentrations and delivered at various flow rates (ii) to examine whether biofilm removal is further improved by a final high‐flow‐rate rinse with an inert irrigant following irrigation with NaOCl. (iii) to simulate the irrigant flow in these areas using a computer model (iv) to examine whether the irrigant velocity calculated by the computer model is correlated to biofilm removal. Methodology: Ninety‐six artificial root canals with either a simulated isthmus or lateral canal were used. A dual‐species in vitro biofilm was formed in these areas using a Constant Depth Film Fermenter. NaOCl at various concentrations (2, 5 and 10%) or adhesion buffer (control) was delivered for 30 s by a syringe and an open‐ended needle at 0.033, 0.083, or 0.166 mL s−1 or passively deposited in the main root canal (phase 1). All specimens were subsequently rinsed for 30 s with adhesion buffer at 0.166 mL s−1 (phase 2). The biofilm was scanned by Optical Coherence Tomography to determine the percentage of the remaining biofilm. Results were analysed by two 3‐way mixed‐design ANOVAs (α = 0.05). A Computational Fluid Dynamics model was used to simulate the irrigant flow inside the artificial root canal system. Results: The flow rate during phase 1 and additional irrigation during phase 2 had a significant effect on the percentage of the remaining biofilm in the isthmus (P = 0.004 and P < 0.001). Additional irrigation during phase 2 also affected the remaining biofilm in the lateral canal significantly (P ≤ 0.007) but only when preceded by irrigation at medium or high flow rate during phase 1. The effect of NaOCl concentration was not significant (P > 0.05). Irrigant velocity in the isthmus and lateral canal increased with increasing flow rate and it was substantially correlated to biofilm removal from those areas. Conclusions: The irrigant flow rate affected biofilm removal in vitro more than NaOCl concentration. Irrigant velocity predicted by the computer model corresponded with the pattern of biofilm removal from the simulated isthmus and lateral canal. [ABSTRACT FROM AUTHOR]

The study of the effects of ultrasound-induced acoustic cavitation on biological structures is an active field in biomedical research. Of particular interest for therapeutic applications is the ability of oscillating microbubbles to promote both cellular and tissue membrane permeabilisation and to improve the distribution of therapeutic agents in tissue through extravasation and convective transport. The mechanisms that underpin the interaction between cavitating agents and tissues are, however, still poorly understood. One challenge is the practical difficulty involved in performing optical microscopy and acoustic emissions monitoring simultaneously in a biologically compatible environment. Here we present and characterise a microfluidic layered acoustic resonator (μLAR) developed for simultaneous ultrasound exposure, acoustic emissions monitoring, and microscopy of biological samples. The μLAR facilitates in vitro ultrasound experiments in which measurements of microbubble dynamics, microstreaming velocity fields, acoustic emissions, and cell-microbubble interactions can be performed simultaneously. The device and analyses presented provide a means of performing mechanistic in vitro studies that may benefit the design of predictable and effective cavitation-based ultrasound treatments. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate the effects of ultrasonic activation file type, lateral canal location and irrigant on the removal of a biofilm‐mimicking hydrogel from a fabricated lateral canal. Additionally, the amount of cavitation and streaming was quantified for these parameters. Methodology: An intracanal sonochemical dosimetry method was used to quantify the cavitation generated by an IrriSafe 25 mm length, size 25 file inside a root canal model filled with filtered degassed/saturated water or three different concentrations of NaOCl. Removal of a hydrogel, demonstrated previously to be an appropriate biofilm mimic, was recorded to measure the lateral canal cleaning rate from two different instruments (IrriSafe 25 mm length, size 25 and K 21 mm length, size 15) activated with a P5 Suprasson (Satelec) at power P8.5 in degassed/saturated water or NaOCl. Removal rates were compared for significant differences using nonparametric Kruskal–Wallis and/or Mann–Whitney U‐tests. Streaming was measured using high‐speed particle imaging velocimetry at 250 kfps, analysing both the oscillatory and steady flow inside the lateral canals. Results: There was no significant difference in amount of cavitation between tap water and oversaturated water (P = 0.538), although more cavitation was observed than in degassed water. The highest cavitation signal was generated with NaOCl solutions (1.0%, 4.5%, 9.0%) (P < 0.007) and increased with concentration (P < 0.014). The IrriSafe file outperformed significantly the K‐file in removing hydrogel (P < 0.05). Up to 64% of the total hydrogel volume was removed after 20 s. The IrriSafe file typically outperformed the K‐file in generating streaming. The oscillatory velocities were higher inside the lateral canal 3 mm compared to 6 mm from WL and were higher for NaOCl than for saturated water, which in turn was higher than for degassed water. Conclusions: Measurements of cavitation and acoustic streaming have provided insight into their contribution to cleaning. Significant differences in cleaning, cavitation and streaming were found depending on the file type and size, lateral canal location and irrigant used. In general, the IrriSafe file outperformed the K‐file, and NaOCl performed better than the other irrigants tested. The cavitation and streaming measurements revealed that both contributed to hydrogel removal and both play a significant role in root canal cleaning. [ABSTRACT FROM AUTHOR]

Background: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations.Methods: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions. Immunohistochemistry was performed on 15 nevi to analyse YAP activation.Results: For 15 out of 16 nevi, a GNAQ/11 mutation was detected in the nevus cells albeit at a low frequency with a median of 13%. Nuclear YAP, a transcriptional co-activator in the Hippo tumour-suppressor pathway, was detected in 14/15 nevi.Conclusions: Our analysis suggests that a mutation in GNAQ/11 occurs in a subset of choroidal nevus cells. We hypothesise that GNAQ/11 mutant-driven extracellular mitogenic signalling involving YAP activation leads to accumulation of wild-type nevus cells. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) is a popular method to assess differences in fiber organization in diseased and healthy muscle tissue. Previous work has shown that muscle DTI measurements depend on signal-to-noise ratio (SNR), %fat, and tissue T2. The goal of this study was to evaluate the potential biasing effects of these factors on skeletal muscle DTI data in patients with Duchenne Muscular Dystrophy (DMD). MR images were obtained of the right lower leg of 21 DMD patients and 12 healthy controls on a Philips 3T system. DTI measurements were combined with quantitative in-vivo measures of mean water T2, %fat and SNR to evaluate their effect on DTI parameter estimation. All outcome measures were determined within ROIs drawn for six lower leg muscles. Between group analysis, using all ROIs, revealed a significantly elevated FA in the GCL, SOL and PER muscles ( p<0.05) and an increased mean diffusivity ( p<0.05) and λ3 ( p<0.05) in the TA muscle of DMD patients. In-vivo evaluation of the individual confounders showed behaviour in line with predictions from previous simulation work. To account for these confounders, subsequent analysis used only ROIs with SNR greater than 20. With this criterion we found significantly greater MD in the TA muscle of DMD patient ( p<0.009) and λ3 in the TA and GCL muscles ( p<0.001) of DMD patients, but no differences in FA. As both increased %fat and lower SNR are expected to reduce the apparent MD and λ3, these between-group differences are likely due to pathophysiology. However, the increased FA, observed when using all ROIs, likely reflects the effect of low SNR and %fat on the DTI parameter estimation. These findings suggest that measuring mean water T2, %fat and SNR is essential to ascribe changes in DTI measures to intrinsic diffusion changes or to confounding influences. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background:Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients and confirmed the findings in an independent validation cohort.Methods:We reanalysed the data from 355 EC patients and tested our findings in an independent validation cohort of 72 patients with EC. Predictors were selected and Harrell's C-index for concordance was used to determine discriminatory power for disease-free survival in the total group and stratified for histological subtype.Results:Predictors for recurrence were FIGO stage, lymphovascular space invasion and numbers of cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells predicted recurrence as well as a combination of FIGO stage and lymphovascular space invasion (C-index 0.67 and 0.71 vs 0.70). Recurrence was best predicted when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells were used in combination (C-index 0.82). Findings were confirmed in the validation cohort.Conclusions:In high-risk EC, clinicopathological or immunological variables can predict regional or distant recurrence with equal accuracy, but the use of these variables in combination is more powerful. [ABSTRACT FROM AUTHOR]

ABSTRACT The use of stem cells for the repair of damaged cardiac tissue after a myocardial infarction holds great promise. However, a common finding in experimental studies is the low number of cells delivered at the area at risk. To improve the delivery, we are currently investigating a novel delivery platform in which stem cells are conjugated with targeted microbubbles, creating echogenic complexes dubbed StemBells. These StemBells vibrate in response to incoming ultrasound waves making them susceptible to acoustic radiation force. The acoustic force can then be employed to propel circulating StemBells from the centerline of the vessel to the wall, facilitating localized stem cell delivery. In this study, we investigate the feasibility of manipulating StemBells acoustically in vivo after injection using a chicken embryo model. Bare stem cells or unsaturated stem cells (<5 bubbles/cell) do not respond to ultrasound application (1 MHz, peak negative acoustical pressure P_ = 200 kPa, 10% duty cycle). However, stem cells which are fully saturated with targeted microbubbles (>30 bubbles/cell) can be propelled toward and arrested at the vessel wall. The mean translational velocities measured are 61 and 177 μm/s for P- = 200 and 450 kPa, respectively. This technique therefore offers potential for enhanced and well-controlled stem cell delivery for improved cardiac repair after a myocardial infarction. Biotechnol. Bioeng. 2015;112: 220-227. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim To introduce and characterize a reproducible hydrogel as a suitable biofilm mimic in endodontic research. To monitor and visualize the removal of hydrogel from a simulated lateral canal and isthmus for the following: I) Ultrasonic-Activated Irrigation (UAI) with water, ii) UAI with NaOCl and iii) NaOCl without UAI. Methodology A rheometer was used to characterize the viscoelastic properties and cohesive strength of the hydrogel for suitability as a biofilm mimic. The removal rate of the hydrogel from a simulated lateral canal or isthmus was measured by high-speed imaging operating at frame rates from 50 to 30 000 fps. Results The hydrogel demonstrated viscoelastic behaviour with mechanical properties comparable to real biofilms. UAI enhanced the cleaning effect of NaOCl in isthmi (P < 0.001) and both NaOCl and water in lateral canals (P < 0.001). A greater depth of cleaning was achieved from an isthmus (P = 0.009) than from a lateral canal with UAI and also at a faster rate for the first 20 s. NaOCl without UAI resulted in a greater depth of hydrogel removal from a lateral canal than an isthmus (P < 0.001). The effect of UAI was reduced when stable bubbles were formed and trapped in the lateral canal. Different removal characteristics were observed in the isthmus and the lateral canal, with initial highly unstable behaviour followed by slower viscous removal inside the isthmus. Conclusions The biofilm-mimicking hydrogel is reproducible, homogenous and can be easily applied and modified. Visualization of its removal from lateral canal anatomy provides insights into the cleaning mechanisms of UAI for a biofilm-like material. Initial results showed that UAI improves hydrogel removal from the accessory canal anatomy, but the creation of stable bubbles on the hydrogel-liquid interface may reduce the cleaning rate. [ABSTRACT FROM AUTHOR]

The root canal system of a tooth is a complex geometrical entity, consisting not only of the main root canal, but also of accessory and lateral canals. Bacteria can reside up to hundreds of micrometers inside those channels and may be difficult to reach for the antimicrobial agents with which root canals are irrigated during a root canal treatment. A combined numerical and experimental study was performed to assess the penetration rate of a root canal irrigant into the lateral canals and tubules, considering both diffusion and convection. The numerical model was validated experimentally using a fluorescent dye. Convection was studied separately using a Computational Fluid Dynamics model, validated with Particle Imaging Velocimetry experiments. Both diffusion and convection were found to be slow on the timescale of an irrigation procedure. The contribution of convection was limited to two canal diameters from the canal entrance, making diffusion the main irrigant transport mechanism. More than 10 min of fresh irrigant delivery was required to obtain an 86 % concentration of the irrigant at the far end of a tubule, in the ideal case of a straight tubule without reaction taking place. Diffusion was even slower when the concentration at the lateral canal entrance was not kept constant, as in the case of a single delivery, which suggests that frequent irrigant replenishment and/or irrigant activation during a root canal treatment are beneficial. Alternative methods should be considered to improve irrigant penetration into lateral canals and tubules. [ABSTRACT FROM AUTHOR]

Ultrasonically activated irrigation is an advanced dental technique for irrigation of the root canal system during a root canal treatment. The basic cleaning mechanism is a result of acoustic streaming induced by an oscillating file, leading to mixing of the irrigant and pressure and shear stresses on the walls of the root canal. Here the induced acoustic streaming, pressure, and shear stress are investigated in a two-dimensional cross-section of the root canal, using a combination of theory, numerical predictions, and experimental validation through high-speed particle tracking velocimetry. Acoustic streaming theory describes very well the flow induced by an ultrasonically oscillating endodontic file. It consists of an oscillatory component, which is dominant near the file, and a steady component, or jet, along the axis of oscillation. The importance of the oscillatory component for both the pressure and the shear stress is apparent, as it is two to three orders of magnitude higher than the steady component. A confinement affects the formation of the steady jets; meanwhile the oscillatory velocities and associated pressure and shear stress are increased. Previous work considering only the steady component of the flow therefore, underestimated the hydrodynamic effects induced by ultrasonic files. [ABSTRACT FROM AUTHOR]

Aim (i) To evaluate the effect of needle type and insertion depth, root canal size and irrigant flow rate on the entrapment of air bubbles in the apical part of a root canal (apical vapor lock) during syringe irrigation using experiments and a Computational Fluid Dynamics ( CFD) model, (ii) to investigate whether the irrigant contact angle affects bubble entrapment, (iii) to examine if an established vapor lock can be removed by syringe irrigation. Methodology Bubble entrapment during irrigation of straight artificial root canals of size 35 or 50 was evaluated by real-time visualizations. The irrigant was delivered by a closed-ended or an open-ended needle positioned at 1 or 3 mm short of working length (WL) and at a flow rate of 0.033-0.260 mL s−1. Results were analysed by nonparametric tests at 0.05 significance. Selected cases were also simulated by a two-phase CFD model. Results A vapor lock was observed in 48% of the cases investigated experimentally. Increasing the apical size, using an open-ended needle, positioning the needle closer to WL and delivering the irrigant at higher flow rate resulted in significantly smaller vapor lock. An increased contact angle resulted in the entrapment of a larger bubble when a low flow rate was used. Both brief insertion of the needle to WL whilst irrigating at a flow rate of 0.083 mL s−1 and delivering the irrigant at 0.260 mL s−1 without changing the needle position were capable of removing an established vapor lock. Conclusions Apical vapor lock may occur under certain conditions, but appears to be easily prevented or removed by syringe irrigation. [ABSTRACT FROM AUTHOR]

Aim To evaluate the effect of multiple refreshment/activation cycles and temperature on the reaction rate of sodium hypochlorite (NaOCl) with bovine dentine during ultrasonic activated irrigation (UAI) under laboratory conditions. Methodology The root canal walls of 24 standardized root canals in bovine incisors were exposed to a standardized volume of NaOCl at different temperatures (24 °C and 38 °C) and exposure times (20, 60 and 180 s). The irrigant was refreshed and ultrasonically activated four times for 20 s followed by a 40 s rest interval, with no refreshment and no activation as the controls. The reaction rate was determined by measuring the amount of active chlorine in the NaOCl solution before and after being exposed to dentine during the specific experimental conditions. Calorimetry was used to measure the electrical-to-sonochemical conversion efficiency during ultrasonic activation. Results Refreshment, activation and exposure time all increased the reaction rate of NaOCl ( P < 0.05). During activation, the temperature of the irrigant increased up to 10 °C. Such temperature rise was insufficient to enhance the reaction rate of NaOCl ( P > 0.125). Conclusions The reaction rate of NaOCl with dentine is enhanced by refreshment, ultrasonic activation and exposure time. Temperature rise of irrigant during ultrasonic activation was not sufficient to alter the reaction rate. [ABSTRACT FROM AUTHOR]

Aim (i) To quantify in a simulated root canal model the file-to-wall contact during ultrasonic activation of an irrigant and to evaluate the effect of root canal size, file insertion depth, ultrasonic power, root canal level and previous training, (ii) To investigate the effect of file-to-wall contact on file oscillation. Methodology File-to-wall contact was measured during ultrasonic activation of the irrigant performed by 15 trained and 15 untrained participants in two metal root canal models. Results were analyzed by two 5-way mixed-design anovas. The level of significance was set at P < 0.05. Additionally, high-speed visualizations, laser-vibrometer measurements and numerical simulations of the file oscillation were conducted. Results File-to-wall contact occurred in all cases during 20% of the activation time. Contact time was significantly shorter at high power ( P < 0.001), when the file was positioned away from working length ( P < 0.001), in the larger root canal ( P < 0.001) and from coronal towards apical third of the root canal ( P < 0.002), in most of the cases studied. Previous training did not show a consistent significant effect. File oscillation was affected by contact during 94% of the activation time. During wall contact, the file bounced back and forth against the wall at audible frequencies (ca. 5 kHz), but still performed the original 30 kHz oscillations. Travelling waves were identified on the file. The file oscillation was not dampened completely due to the contact and hydrodynamic cavitation was detected. Conclusion Considerable file-to-wall contact occur-red during irrigant activation. Therefore, the term ' Passive Ultrasonic Irrigation' should be amended to ' Ultrasonically Activated Irrigation'. [ABSTRACT FROM AUTHOR]

Spatio-temporal magnetic field changes in the brain caused by breathing or body movements can lead to image artifacts. This is especially a problem in T2*-weighted sequences. With the acquisition of an extra echo (navigator), it is possible to measure the magnetic field change induced frequency offset for a given slice during image acquisition. However, substantial local variation across a slice can occur. This work describes an extension of the conventional navigator technique that improves the estimation of the magnetic field distribution in the brain during strong field fluctuations. This is done using the combination of signals from multiple coil elements, the coil sensitivity profiles, and frequency encoding: termed sensitivity-encoded navigator echoes. In vivo validation was performed in subjects who performed normal breathing, nose touching, and deep breathing during scanning. The sensitivity-encoded navigator technique leads to an error reduction in estimating the field distribution in the brain of 73% ± 16% compared with 56% ± 14% for conventional estimation. Image quality can be improved via incorporating this navigator information appropriately into the image reconstruction. When the sensitivity-encoded navigator technique was applied to a T2*-weighted sequence at 7 T, a ghosting reduction of 47% ± 13% was measured during nose touching experiments compared with no correction. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

During a root canal treatment the root canal is irrigated with an antimicrobial fluid, commonly performed with a needle and a syringe. Irrigation of a root canal with two different types of needles can be modeled as an impinging axisymmetric or non-axisymmetric jet. These jets are investigated experimentally with high-speed Particle Imaging Velocimetry, inside and outside the confinement (concave surface) of a root canal, and compared to theoretical predictions for these jets. The efficacy of irrigation fluid refreshment with respect to the typical reaction time of the antimicrobial fluid with a biofilm is characterized with a non-dimensional Damköhler number. The pressure that these jets induce on a wall or at the apex of the root canal is also measured. The axisymmetric jet is found to be stable and its velocity agrees with the theoretical prediction for this type of jet, however, a confinement causes instabilities to the jet. The confinement of the root canal has a pronounced influence on the flow, for both the axisymmetric and non-axisymmetric jet, by reducing the velocities by one order of magnitude and increasing the pressure at the apex. The non-axisymmetric jet inside the confinement shows a cascade of eddies with decreasing velocities, which at the apex does not provide adequate irrigation fluid refreshment. [ABSTRACT FROM AUTHOR]

Boutsioukis C, Gogos C, Verhaagen B, Versluis M, Kastrinakis E, van der Sluis LWM. The effect of apical preparation size on irrigant flow in root canals evaluated using an unsteady Computational Fluid Dynamics model. International Endodontic Journal, 43, 874–881, 2010. Aim To evaluate the effect of apical preparation size on irrigant flow inside a root canal during final irrigation with a syringe and two different needles types, using a Computational Fluid Dynamics (CFD) model. Methodology A validated CFD model was used to simulate the irrigant flow from either a side-vented or a flat 30G needle positioned inside root canals having sizes of 25, 35, 45 and 55, all with a .06 taper, at 3 mm short of working length (WL). Velocity, pressure and shear stress in the root canal were evaluated. Results Different preparation sizes resulted in minor differences in the flow pattern in the apical root canal. Major differences were observed between the two needle types. The side-vented needle could not achieve irrigant replacement to the WL even in a size 55, .06 taper root canal. Significant irrigant replacement was evident almost to the WL in size 35, 45 and 55, .06 taper root canals with the flat needle. The maximum shear stress decreased as the preparation size increased. The flat needle developed higher mean pressure at the apical foramen. Both needles led to a similar gradual decrease in apical pressure as the preparation size increased. Conclusions Apical preparation size affected irrigant replacement, the shear stress on the canal wall and the pressure at the apical foramen. Root canal enlargement to sizes larger than 25 appeared to improve the performance of syringe irrigation. Adequate space between the needle and the canal wall should be ensured to allow for an effective reverse flow of the irrigant towards the canal orifice. [ABSTRACT FROM AUTHOR]

Boutsioukis C, Gogos C, Verhaagen B, Versluis M, Kastrinakis E, van der Sluis LWM. The effect of root canal taper on the irrigant flow: evaluation using an unsteady Computational Fluid Dynamics model. International Endodontic Journal, 43, 909–916, 2010. Aim To evaluate the effect of root canal taper on irrigant flow inside a prepared root canal during final irrigation with a syringe and two types of needles, using a Computational Fluid Dynamics (CFD) model. Methodology A validated CFD model was used to simulate irrigant flow from either a side-vented or a flat 30G needle positioned inside size 30, .02 taper, 30, .04, 30, .06, ProTaper F3 or size 60, .02 taper root canals, at 3 mm short of working length (WL). Velocity, pressure and shear stress in the root canal were evaluated. Results The side-vented needle could not achieve irrigant replacement to the WL in any of the cases. Significant irrigant replacement was evident further than 2 mm apically to the tip of the flat needle in the size 30, .06 taper, F3 and size 60, .02 taper canal. A wider distribution of wall shear stress was noted as the canal taper increased but the maximum shear stress decreased. The flat needle led to higher mean pressure at the apical foramen. Both needles showed a similar gradual decrease in apical pressure as the taper increased, but the least pressure was calculated in the size 60, .02 taper canal. Conclusions An increase in root canal taper improved irrigant replacement and wall shear stress whilst reducing the risk for irrigant extrusion. Irrigant flow in a minimally tapered root canal with a large apical preparation size also improved irrigant replacement and wall shear stress and reduced the risk for irrigant extrusion, compared to the tapered root canals with a smaller apical preparation size. [ABSTRACT FROM AUTHOR]

Boutsioukis C, Verhaagen B, Versluis M, Kastrinakis E, van der Sluis LWM. Irrigant flow in the root canal: experimental validation of an unsteady Computational Fluid Dynamics model using high-speed imaging. International Endodontic Journal 43, 393–403, 2010. Aim To compare the results of a Computational Fluid Dynamics (CFD) simulation of the irrigant flow within a prepared root canal, during final irrigation with a syringe and a needle, with experimental high-speed visualizations and theoretical calculations of an identical geometry and to evaluate the effect of off-centre positioning of the needle inside the root canal. Methodology A CFD model was created to simulate irrigant flow from a side-vented needle inside a prepared root canal. Calculations were carried out for four different positions of the needle inside a prepared root canal. An identical root canal model was made from poly-dimethyl-siloxane (PDMS). High-speed imaging of the flow seeded with particles and Particle Image Velocimetry (PIV) were combined to obtain the velocity field inside the root canal experimentally. Computational, theoretical and experimental results were compared to assess the validity of the computational model. Results Comparison between CFD computations and experiments revealed good agreement in the velocity magnitude and vortex location and size. Small lateral displacements of the needle inside the canal had a limited effect on the flow field. Conclusions High-speed imaging experiments together with PIV of the flow inside a simulated root canal showed a good agreement with the CFD model, even though the flow was unsteady. Therefore, the CFD model is able to predict reliably the flow in similar domains. [ABSTRACT FROM AUTHOR]

Aim To test ex vivo the efficiency of laser-activated irrigation in removing dentine debris from the apical part of the root canal and to visualize in vitro the fluid dynamics during the activation of the irrigant by laser, using high-speed imaging at a relevant timescale. Methodology Root canals with a standardized groove in one canal wall filled with dentine debris were irrigated with syringe irrigation, ultrasonically or laser-activated irrigation (LAI) using 2% sodium hypochlorite as irrigant. The quantity of dentine debris after irrigation was determined. Visualization of the fluid dynamics during activation was achieved using a high-speed camera and a glass model. Results Laser-activated irrigation was significantly more effective in removing dentine debris from the apical part of the root canal than passive ultrasonic irrigation or hand irrigation when the irrigant was activated for 20 s. Conclusions The in vitro recordings suggest that streaming, caused by the collapse of the laser-induced bubble, is the main cleaning mechanism of LAI. [ABSTRACT FROM AUTHOR]

Background: Adenosine is a signalling nucleoside that has been proposed to contribute to the pathogenesis of asthma. Adenosine is produced in inflammatory environments and acts via adenosine receptors (A1R, A2AR, A2BR, and A3R) expressed by a wide variety of cells, resulting in pro- and anti-inflammatory effects. Objective: To compare AR expression in asthma patients and healthy subjects, and to assess the effect of allergen challenge on AR expression of inflammatory cells and on cytokines in peripheral blood and sputum in asthma. Methods: Asthma patients underwent an allergen challenge, and blood and induced sputum samples were taken before and 24 h after allergen challenge to study inflammatory cells numbers, AR expression and cytokine production. Blood and sputum were investigated at one time point in healthy subjects. AR expression was measured by flow cytometry (blood) or on cytospins using immunocytochemistry (sputum). Cytokines (luminex, ELISA) and adenosine (HPLC) were measured in sputum supernatant. Results: The percentage of A2BR expressing neutrophils in sputum was lower in asthma patients than in healthy subjects ( P = 0.016). Allergen challenge decreased A1R and A2AR expression on neutrophils and A1R expression on T cells in peripheral blood (all P < 0.05). Allergen challenge increased IL-8 levels and eosinophil numbers ( P < 0.05), whereas it decreased thymic stromal lymphopoietin levels and the percentage of A1R expressing macrophages in induced sputum ( P < 0.05). Conclusions: Allergen challenge has a down-regulatory effect on AR expression in asthma, suggesting a contribution of adenosine-related effector mechanisms in the pathophysiology. [ABSTRACT FROM AUTHOR]

Ultrasonic irrigation of the root canal can be performed with or without simultaneous ultrasonic instrumentation. When canal shaping is not undertaken the term passive ultrasonic irrigation (PUI) can be used to describe the technique. In this paper the relevant literature on PUI is reviewed from a MEDLINE database search. Passive ultrasonic irrigation can be performed with a small file or smooth wire (size 10–20) oscillating freely in the root canal to induce powerful acoustic microstreaming. PUI can be an important supplement for cleaning the root canal system and, compared with traditional syringe irrigation, it removes more organic tissue, planktonic bacteria and dentine debris from the root canal. PUI is more efficient in cleaning canals than ultrasonic irrigation with simultaneous ultrasonic instrumentation. PUI can be effective in curved canals and a smooth wire can be as effective as a cutting K-file. The taper and the diameter of the root canal were found to be important parameters in determining the efficacies of dentine debris removal. Irrigation with sodium hypochlorite is more effective than with water and ultrasonic irrigation is more effective than sonic irrigation in the removal of dentine debris from the root canal. The role of cavitation during PUI remains inconclusive. No detailed information is available on the influence of the irrigation time, the volume of the irrigant, the penetration depth of the instrument and the shape and material properties of the instrument. The influence of irrigation frequency and intensity on the streaming pattern as well as the complicated interaction of acoustic streaming with the adherent biofilm needs to be clarified to reveal the underlying physical mechanisms of PUI. [ABSTRACT FROM AUTHOR]

Abstract. We report a series of Raman-Rayleigh-LIF measurements in two turbulent natural-gas jet diffusion flames produced by the Delft piloted jet diffusion flame burner. The main objective of the Raman-Rayleigh-LIF measurements was to obtain detailed information on the major species concentrations in the flames. The measurements provide simultaneous data on temperature, the concentrations of the major species and the radicals OH and NO and mixture fraction. The application of the Raman technique in the undiluted naturalgas flames proves to be very challenging because of the high fluorescence interference levels. The interference contributions to the recorded Raman signals are identified and subtracted using empirical correlations between the Raman signals and the signals on fluorescence interference monitor channels. The calibration and data reduction of the RamanRayleigh and LIF signals are discussed in detail. The resulting dataset compares excellently with data from previous experiments. Because the Raman-Rayleigh-LIF data provide quantitative concentrations and accordingly quantitative mixture fractions, they form a valuable and useful extension of the existing database tot the Delft piloted jet diffusion flame burner. [ABSTRACT FROM AUTHOR]

This paper describes a tunable far-infrared (FIR) spectrometer. Tunable radiation is obtained by frequency mixing, fixed frequency FIR laser radiation and tunable microwave radiation in Schottky barrier diodes. An optically pumped laser and an HCN discharge laser are used as FIR sources and klystrons in the frequency range of 22–114 GHz as microwave sources. This yields an 85% coverage of the frequency region between 550 and 2700 GHz. Up to sixth order sidebands have been generated and used for spectroscopy. The ultimate sensitivity corresponds to a minimum detectable fractional absorption of 10-5 at 1-s RC time. The applicability of the spectrometer in high-resolution spectroscopy of transient species has been demonstrated by the observation of spectra of OD and N2H+. New laser emissions of optically pumped CH2F2 have been found and accurate frequencies have been determined for some of them. [ABSTRACT FROM AUTHOR]

A technique has been developed to measure the absolute OH concentration at atmospheric pressures by using a combination of direct absorption and laser-induced fluorescence (LIF) detection. The technique is independent of collisions, because it uses laser beams in a bi-directional configuration, thereby eliminating collisional quenching. The absolute OH concentration is measured spatially resolved in two dimensions by using absorption on the Q[sub 1] (6) rotational line in the A[sup 2] Σ[sup +] (v[sup ′] =0)←X[sup 2] Π(v[sup ′′] =0) band of OH at 309 nm. The requirements for obtaining a good signal-to-noise ratio for the technique are discussed and the possibilities of single-shot measurements are investigated. [ABSTRACT FROM AUTHOR]

A tunable excimer laser at 248 nm (KrF) and 193 nm (ArF) has been used to monitor two-dimensional OH and NO distributions in the turbulent flame of a 100 kW natural gas burner. Spatially resolved fluorescence (spatial resolution better than 1.0 mm) from a 20 cm×20 cm area is collected under single shot conditions. We describe the problems encountered when laser-induced fluorescence imaging techniques are applied to large scale flames. Special experimental arrangements, imposed by the turbulent behavior of the flame we used, are also described. [ABSTRACT FROM AUTHOR]

Liver from 14 day-old fetuses, bone marrow, spleen, and blood from normal adult mice, and bone marrow, spleen, blood, and liver from adult endotoxin (ET)-treated mice were used for isogeneic hemopoietic restoration in lethally whole-body irradiated mice. The number of CFU-S required to prevent 50% mortality of irradiated mice was about 3 for fetal liver, 7-10 for bone marrow, 20 for normal blood and for blood, liver, and spleen of ET-treated mice, and 80 for spleen of normal mice. CFU-S growth curves in femoral bone marrow and spleen showed some variations but the differences in survival of irradiated and protected mice could not easily be explained by differences in CFU-S growth curves. It can be concluded that the CFU-S from peripheral blood, although somewhat less effective than CFU-S from bone marrow, can be a valuable source of CFU-S for bone marrow transplantation. [ABSTRACT FROM AUTHOR]

Dopamine causes a dose-dependent contraction of the rat rectum in vitro followed by a relaxation. This contraction can be inhibited by apomorphine and phenylephrine. This inhibition can be attenuated by the β-endorphin (βE) fragments 2-17 (des-Tyr-γ-endorphin, DTγE) and 6-17 (des-enkephalin-γ-endorphin, DEγE). βE 6-17 seems to be the shortest sequence with full activity in this respect since a shorter fragment (βE 10-17) was less effective. The atypical neuroleptics oxypertine, sulpiride, and clozapine, the classic neuroleptic haloperidol and metoclopramide have a similar action to DEγE. The peptides and atypical neuroleptics do not affect the dopamine response per se while the classic neuroleptics haloperidol and metoclopramide enhance the dopamine response. The effects of the α-type endorphins are opposite to those of the γ-type endorphins, since des-Tyr-α-endorphin (DTαE, βE 2-16) and des-enkephalin-α-endorphin (DEαE, βE 6-16) enhance the phenylephrine-induced decreased responsiveness to dopamine. Structure-activity studies revealed that the active moiety of the α-endorphin fragments probably resides in the 6-9 region. In addition the α-type endorphins directly inhibit the dopamine response. It is concluded that the rat rectum may be used to analyse neuroleptic-like action. In this model α- and γ-endorphin fragments may directly or indirectly influence the interaction of dopamine with the rectum. Because of the strong similarities between the effects of γ-type endorphins and that of neuroleptics the results support the purported neurolepticlike action of γ-type endorphins. The influence of α-type endorphins and γ-type endorphins on the apomorphine or phenylephrine induced decreased responsiveness to dopamine, although opposite, seems to be mediated by an influence on different dopamine sensitive systems. [ABSTRACT FROM AUTHOR]

The authors report optical observations of the change in the dynamics of one and the same ultrasound contrast agent microbubble due to the influence of interfaces and neighboring bubbles. The bubble is excited by a 2.25 MHz ultrasound burst and its oscillations are recorded with an ultrahigh-speed camera at 15 million frames per second. The position of an individual bubble relative to a rigid wall or second bubble is precisely controlled using optical tweezers based on Laguerre-Gaussian laser beams [P. Prentice et al., Opt. Express 12, 593 (2004); V. Garbin et al., Jpn. J. Appl. Phys. 44, 5773 (2005)]. This allows for repeated experiments on the very same bubble and for a quantitative comparison of the effect of boundaries on bubble behavior. [ABSTRACT FROM AUTHOR]