br Neoadjuvant androgen deprivation therapy ADT represents one of

Neoadjuvant androgen-deprivation therapy
ADT represents one of the original targeted therapies for cancer (Fig. 1). Two decades of trials testing neoadjuvant ADT alone or combined with chemotherapy have demonstrated that this treatment can induce measureable changes in the local disease burden at the time of surgery (recent, prospective, randomized controlled trials are summarized in Table 1). Though end points differed between studies, they generally included higher rates of organ-confined disease, reduced rates of extracapsular extension, and reduced rates of positive surgical margins. Affected systemic end points included reduced incidence of SW033291 node involvement, reduced testosterone levels, and PSA responses. Unfortunately, improved local control rates obtained in these trials did not translate into OS benefits; granted, the majority of these studies were underpowered to detect statistically significant differences in biochemical relapse-free survival.
Schulman and colleagues were among the first to report on both progression-free survival (PFS) and OS in a large, randomized trial of neoadjuvant ADT [6]. This study randomized 402 men with clinical T2 or T3 localized prostate cancer to receive either 3 months of total androgen deprivation with neoadjuvant goserelin plus flutamide before RP or RP alone. The rates of pathologic downstaging in the neoadjuvant ADT group compared with the prostatectomy alone group were 15% and 7% (P<0.01), and the positive surgical margin rates were 47.5% and 26.3% (P<0.05), respectively. After 4 years of follow-up, there were no significant differences in biochemical progression-free survival (67% vs. 76%, P = 0.18) or OS (95% vs. 94%, P =0.64) between the 2 treatment groups. Kumar et al. [7] performed a systematic review and meta-analysis of neoadjuvant hormone therapy in localized or locally advanced prostate cancer. Overall, 10 randomized clinical trials testing the role of hormonal therapy given before prostatectomy between 1966 and 2006 were included. Only 3 of the trials provided OS data, and 5 provided biochemical progression-free survival data. The authors showed that neoadjuvant hormonal therapy before prostatectomy did not improve OS (OR = 1.11; 95% CI: 0.67–1.85; P = 0.69) despite significant reductions in the positive surgical margin rates (OR = 0.34; 95% CI: 0.27–0.42; P<0.00001) and significant improvements in other clinical outcome measures including lymph node involvement, pathologic staging, and organ-confined rates. Neoadjuvant treatment resulted in a borderline significant reduction in disease recurrence rates (OR = 0.74; 95% CI: 0.55–1.0; P = 0.05). The authors concluded that neoadjuvant hormone therapy given before prostatectomy is associated with significant clinical benefits in the form of improved local control but does not result in improved OS. As a result, neoadjuvant ADT before prostatectomy is not considered the standard of care. One possible reason for the lack of survival benefit was the short 3-month duration of treatment used in most of the studies. We now know from the neoadjuvant-EBRT experience in high-risk prostate cancer that longer duration (3y) of androgen suppression is associated with improved outcomes [4]. In the study by Gleave, 8 months of preoperative ADT was compared with 3 months (Table 1) and showed a significant reduction in the rate of positive surgical margins from 23% to 12% (P = 0.0106) with longer duration of ADT; mean serum PSA decreased by 98% after 3 months, with a further 57% decrease from 3 to 8 months. Although this suggested that 3 months of ADT was insufficient to achieve optimal local control, survival data were not reported, so conclusions regarding the ideal length of preoperative ADT could not be determined from this study [8].
The reasons for the failure of neoadjuvant ADT to improve survival are unclear and complex. However, the biology of castration-resistant prostate cancer (CRPC), defined as progressive disease despite castrate levels of testosterone (less than 50ng/dl), has taught us that despite maximum suppression of androgen synthesis and activity using LHRH agonists/antagonists and antiandrogens, residual levels of testosterone are sufficient to drive continued growth of prostate cancer left behind with surgery. It is possible that the degree of androgen suppression achieved with these medications was not profound enough to ultimately affect survival rates. Abiraterone is a novel first-in-class inhibitor of 17α-hydroxylase/C17, 20-lyase (CYP17), a critical enzyme in testicular, adrenal, and tumor androgen biosynthesis (Fig. 1). By suppressing androgen synthesis beyond what is achievable using LHRH agonists and antagonists, abiraterone was shown to increase PFS and OS in men with metastatic CRPC in both the pre– and post–docetaxel administration patient populations [9,10]. A neoadjuvant trial combining abiraterone with leuprolide has since been performed [11]. Overall, 58 men with high-risk prostate cancer (cT3–T4, Gleason score greater than or equal to 7, PSA greater than or equal to 20ng/ml, or PSA velocity greater than 2ng/ml/y) were randomized to receive treatment with abiraterone plus prednisone in combination with leuprolide or leuprolide alone for the first 12 weeks. All patients then subsequently received an additional 12 weeks of combined abiraterone plus prednisone with leuprolide before prostatectomy for 24 weeks of treatment. The primary end point of the study was a comparison of intraprostatic testosterone (and DHT) levels in interim prostate biopsies obtained at 12 weeks. The secondary end points of PSA, pathologic complete response (pCR), and near pCR (less than or equal to 5mm of residual tumor) were assessed on the surgical specimen. Patients receiving the 24 weeks of abiraterone treatment had a trend toward improved combined pCR/near pCR rates (34% vs. 15%, P = 0.0894) compared with those treated with abiraterone for only the final 12 weeks. These results suggest that abiraterone may enhance the potency of traditional androgen deprivation in early prostate cancer and provide a rationale to further study this combination in that disease setting.

Several years ago NASA s Global Modeling and

Several years ago, NASA\’s Global Modeling and Assimilation Office (GMAO) introduced the Modern-Era Retrospective Analysis for Research and Application (MERRA, Rienecker et al., 2011), a reanalysis tool incorporating satellite and model data to reproduce spatially consistent observations of many environmental variables. While the original MERRA included only meteorological parameters (wind, temperature, humidity, etc.), it has recently been extended to include assimilation of biased-corrected aerosol optical depth (AOD) from the Moderate Resolution Imaging Spectroradiometers sensors (MODIS, Remer et al., 2005) on board the Aqua and Terra satellites, which led to its rebranding as MERRAero. Although only total AOD is constrained by MODIS observations, the data assimilation algorithm in MERRAero provides speciated hourly data, with the relative contributions from five of the major aerosol species listed previously. Version 1 of MERRAero doesn\’t assimilate NO3 particles. Nevertheless, MERRAero provides an innovative tool to the scientific Sennoside A to study aerosol pollution issues around the world, especially in regions where reliable surface-based monitoring is scarce or unavailable. Examples of MERRAero\’s applicability can be found in Kessner et al. (2013), Colarco et al. (2014), Kishcha et al. (2014, 2015) and Yi et al. (2015).
In this study, AOD data from MERRAero is used to assess the state of air quality over a large selection of major metropolitan areas around the world (hereafter simply referred to as “cities”) over the last thirteen years (2003–2015). Speciation data is used to determine which aerosol species contribute most to AOD over each city and a trend analysis is performed to evaluate how local and regional factors, as well as natural and anthropogenic factors, affect aerosol pollution in urban environments. Alpert et al. (2012) previously and similarly analyzed AOD trends over a selection of major cities around the world based on MODIS data. The advantage of using MERRAero as opposed to just MODIS data is its ability to distinguish between aerosol species which provides substantially more information for analysis.

Methodology and data

Discussion and conclusion
The mean AOD was high (>0.3) in most cities of China, India, the Middle East, Northern and tropical Africa. In contrast, it was relatively low (< 0.2) in most cities of North America, South America, Europe, Australia and South Africa. The high AOD values observed in Northern African and Western Asian cities are caused mostly by their proximity to large and sandy deserts. Advection of DS also affects cities in India and Bangladesh but the high AOD averages in cities of these two countries is mostly the result of anthropogenic activities. Fossil fuel burning is responsible, for the most part, for the high AOD values observed in Chinese cities. However, advection of dust affects to some extent the AOD in cities of Northern China as well. High AOD averages in cities of tropical Africa are caused by deforestation and biomass burning activities.
Cities in North America, Europe, Japan, Southeastern Asia and Oceania tend to have a relatively low AOD on average, while SO4 and POM aerosols contribute to it most. Even though fossil fuel consumption is a major source of pollution in those parts of the world, effective air quality regulations have been successful at keeping emissions and, as a consequence, AOD values low over the last decade. Cities in South America and on the west coast of the U.S. are affected by fossil fuel burning but carbon emissions from wildfires contribute a significant proportion to their mean AOD during the summer. European cities are also affected by DS transport from the Sahara.
Overall, SO4 aerosols represented at least 10% of the mean AOD in all but two of the 200 cities presented in the various maps of this manuscript, those of Dakar in Senegal and Kano in Nigeria, for the only reason that their AOD is overwhelmed by DS particles due to their location close to the Sahara. POM aerosols represented at least 10% of the average in all but 24 cities, mostly located in Northern Africa or Western Asia. The presence of SS aerosols is significant in coastal cities but usually contributes little to the mean AOD.

Several previous research works have discussed the advantages of stable

Several previous research works have discussed the advantages of stable tunnel excavation and the mechanisms of auxiliary methods. Since tunnels are often driven through soft ground containing groundwater and in locations close to various utilities and structures, Kimura, Ito, Iwata, and Fujimoto (2005) applied two methods, namely, special jet grouting for foot piles and long steel pipe fore-piling for preventing displacement, and a boring method for groundwater drainage. Oke, Valchopoulos, and Marinos (2014) analyzed literature and construction reports and discussed the effect of the umbrella arch (UA) by classifying three types of support elements: spiles, forepoles and grouted. Yoo (2002) investigated the behavior of a tunnel face reinforced by longitudinal pipes using a 3D finite quinacrine analysis. Based on the numerical results, he concluded that the face-reinforcement technique using longitudinal pipes could significantly reduce the deformation of the face and thus improve its stability. Kamata and Mashimo (2003) researched the effects of several auxiliary methods, such as face bolting, vertical pre-reinforcement bolting and forepoling, through centrifugal modeling tests on sandy ground and numerical simulation with DEM. They identified several favorable effects in terms of face stability. Taguchi et al. (2000) conducted model and full-size tests on a thin flexible pre-lining. They concluded that the pre-lining was effective for both the stability of the face and the prevention of ground surface settlement. They also proposed a quantitative estimation method for face stability. Kitagawa et al. (2009, 2010) performed trapdoor experiments and a numerical simulation to determine the effect of a reduction in settlement and the corresponding mechanism using a tunnel foot reinforcement side pile. Cui, Kishida, and Kimura (2008) performed numerical simulation of a tunnel excavation and a side pile with the aim to prevent surface settlement of the shallow overburden and the soft ground. Based on the numerical simulation, they proposed that the prevention of ground surface settlement and tunnel settlement, by the installation of a foot reinforcement side pile, affects the shear reinforcement, the load redistribution and the internal quinacrine pressure. They also advised that the foot reinforcement side pile should be installed across the shear zone during tunnel excavation.
Several tunnels constructed for the Tohoku bullet train in Japan, the so-called Tohoku Shinkansen Railway, between Hachinohe and Shichinohe-Towada, were constructed under the condition of shallow overburden and soft ground. In cases without any obstacles on the ground surface, the objective ground was improved using the shallow or deep mixing stabilization method. Then, the tunnel was excavated by NATM. This approach constitutes the ground improvement method of the excavation of a shallow overburden tunnel. Fig. 1 shows the construction process associated with this method. First, the ground is excavated to the upper part of the tunnel crown. Then, cement is mixed with the natural ground around the sidewall of the tunnel using the shallow or the deep mixing stabilization method. The premixed soil is spread and compacted by rolling it over the tunnel crown area. Finally, the excavated soil is backfilled and compacted by rolling it to the ground surface. The tunnel can then be excavated using NATM. Various combinations of improved areas and levels of strength of the improved ground were implemented in the field, and the tunnels were excavated successfully. The ground improvement method was employed after considering the conditions of the overburden, the geology, the ground surface, the allowed settlement, and data from several previously reported construction projects (Kitagawa, Isogai, Okutsu, & Kawaguchi, 2004; Nonomura, Iura, Okajima, & Kishida, 2011; Saito, Ishiyama, Tano, & Haga, 2011; Tadenuma, Isogai, Konishi, Nishiyama, & Okutsu, 2003). Without disturbing any buildings and houses on the surface, this method has the advantage of pre-knowledge of the geological structure. Consequently, this method is more advantageous in terms of construction costs than other auxiliary methods, as shown in Fig. 2.

As revealed by the analysis of clots retrieved from ischemic

As revealed by the analysis of clots retrieved from ischemic stroke patients (Liebeskind et al. 2011; Marder et al. 2006), the main components of clots are red blood acetanilide (RBC), fibrin and platelets. An important issue in the clot lysis process is the effect of STL on the fibrin network. Fibrin strands provide a 3-D scaffold for the intravascular clot and ensure its stability against mechanical stress and degradation (Mosesson 2005; Weisel 2007). Therefore, degradation of the fibrin network is a key factor in the success of STL therapy, and its monitoring is essential.
In a previous study (Petit et al. 2015), we used two different quantification techniques to assess fibrin degradation: measurement of radiolabeled-fibrin degradation products (FDP) and D-dimer assay. It was found that at high acoustic pressure, the combination of ultrasound (US) and MB was not able to degrade the fibrin network in the absence of a thrombolytic drug. On the contrary, a clear synergistic effect was observed on fibrin degradation when US, MB and recombinant tissue plasminogen activator (rtPA) were associated.
Even though the respective roles of microstreaming and microjets in MB-enhanced STL remain unclear, it is commonly recognized that cavitation-based phenomena play an important role in the clot dissolution process, as reported by some authors (Datta et al. 2008; Hitchcock et al. 2011; Prokop et al. 2007; Shi et al. 2010; Xie et al. 2011). Indeed the argument for using MB to enhance US action is that MB dramatically reduce the acoustic cavitation threshold by providing cavitation nuclei in the medium. Cavitation could induce direct mechanical damage to the clot as well as positively affect the action of rtPA by improving access to fibrin strands and drug transport. For example, Prokop et al. (2007) reported that in the presence of a thrombolytic drug, the enhancement of clot lysis is related to the cavitation activity caused by the combination of US and MB. Historically, cavitation activity has been classified as either stable or inertial (Neppiras 1980). Stable cavitation (SC) designates the stable oscillation of MB over time in response to applied acoustic waves (Miller et al. 1996) and induces microstreaming (Collis et al. 2010; Leighton 1994; Wu and Nyborg 2008). At higher acoustic pressures, inertial cavitation (IC) occurs, and MB undergo a rapid increase in size followed by violent bubble collapse (Miller et al. 1996). Inertial cavitation produces a more violent mechanical action, such as microjets, but within a much shorter period than SC action (Holland and Apfel 1990; Miller et al. 1996).
Whether SC or IC would be more appropriate for STL is still debated. For instance, Datta et al. (2008) observed a significant correlation between clot lysis and SC activity with 120-kHz US and MB. Hitchcock et al. (2011) later reported significant enhancement of rtPA-induced lysis by US and MB, with US parameters selected to have maximal SC exposure. Thus, these studies emphasize the contribution of SC in MB-enhanced STL. Although the experiments were designed to maximize SC phenomena, IC was also present in these studies, which underlines the complexity of discriminating the effect of each type of cavitation.


For all experiments, clot lysis was assessed as diameter loss (mm) and 125I-FDP release (%) after 60 min of treatment. The results are illustrated in Figure 2(a, b).
For the control (plasma only), no significant diameter loss (0.02 ± 0.01 mm) or 125I-FDP release (0.3 ± 0.1%) was observed. This was a sign of good clot stability for the duration of the experiment. In the group exposed to rtPA alone, a diameter loss of 0.39 ± 0.01 mm was measured, with a corresponding 125I-FDP release of 51.7 ± 2.0%, this being the mark of efficient enzymatic fibrinolysis.
Figure 2a also illustrates that for all conditions combining rtPA + US + MB, diameter loss was significantly increased compared with that for rtPA alone. Examples of typical treated clots are illustrated in Figure 3a. Considering fibrin degradation (Fig. 2b), under the condition of SC only (200 kPa, 500 ms ON/750 ms OFF), no enhancement of 125I-FDP release was observed (53.2 ± 0.9%, p > 0.05 vs. rtPA). Under the condition of coexisting SC and IC (350 kPa, 100 ms ON/1,150 ms OFF), fibrin degradation was significantly enhanced compared with rtPA (57.2 ± 2.9%, p < 0.001). Additionally, histological analysis revealed multiple small areas lacking RBC in the area exposed to US (Fig. 4c). Interestingly, at 350 kPa, when the pulse length was reduced from 100 to 1 ms, the increase in fibrin degradation provided by US + MB was lost (50.9 ± 1.9%, p > 0.05 vs. rtPA). Finally, at 1,300 kPa (1 ms ON/1,249 ms OFF), inducing essentially IC, there was an absolute increase of 15% (p < 0.001 versus rtPA) in fibrin degradation. Note that the lysis was almost complete in the central part of the clot (Fig. 3a).

Bindarit Supplier The results were viewed in two

The results were viewed in two ways. First, to indicate the changes in PCH with exposure, PCH areas were plotted against PRPA (Fig. 3) and ISPPA. By linear regression, the PCH areas increased rapidly with exposure above an intercept. The linear regression included all positive results, which ranged from 2 to 4 points for the different conditions. The intercepts are listed in Table 3 together with the coefficients of determination for the linear regressions. Remarkably, all exposure conditions had about the same intercepts of ∼0.73 MPa and ∼20 W/cm2.
Second, the proportion of rats with positive results was determined for each group, and the statistical significance of the occurrence was determined from the z-test of proportions, as listed in Table 2. Thresholds were determined as the mean of the lowest exposure setting with statistically significant occurrence of PCH and the next lower setting, as listed in Table 3 for PRPA,

and ISPPA. Threshold spatial-peak temporal-average intensity (ISPTA) values were low: for groups A and B, the duty Bindarit Supplier was 4.12 × 10−4. ISPTA thresholds, for example, for groups A and B, were therefore 8.8 and 7.5 mW/cm2, respectively. A multiple pairwise comparison revealed that thresholds for conditions A, B and D did not significantly differ, and likewise for conditions C and E. However, condition A, B and D thresholds, at about 0.7 MPa, were significantly lower (p < 0.01) than condition C and E thresholds, at about 1.15 MPa. This relative difference also was found for statistical comparisons of the thresholds in terms of

and ISPPA (Table 3).

Five different pulsed-ultrasound Bindarit Supplier exposure conditions were investigated in terms of PCH area and occurrence (Table 1). For each condition, four groups were exposed for 5 min at a range of PRPA values including the PCH thresholds (Table 2). Groups A and B compared 1.5 MHz with 7.5 MHz with same pulse mode of 10-μs pulses at 25 ms. The use of identical pulse timing eliminated the increases in PRPA thresholds previously seen for higher frequencies with DUS pulses of shorter duration (Table 4). These results indicated that ultrasonic frequency per se did not affect the threshold results, but pulse duration and other timing parameters did. The use of modulated pulse modes, which simulated DUS exposure to some extent, resulted in higher occurrence thresholds (Table 3). The value of PRPA divided by the square root of frequency was 0.98 MPa/MHz½ at 1.5 MHz and 0.41 MPa/MHz½ at 7.5 MHz. However, when longer pulses of 12 cycles (1.5-μs duration at 7.5 MHz) were used, compared with 2 or 3 cycles (0.3 μs at 7.5 MHz or 1.7 μs at 1.5 MHz), the threshold was comparable to that of the non-modulated groups.
When the PCH area results were analyzed by linear regression, all the conditions tested had nearly the same PRPA intercept (Fig. 3), a noteworthy lack of variation for the varied conditions. The 7.5-MHz beam size was much smaller than the 1.5-MHz beam size (Table 1), which resulted in smaller PHC areas at 7.5 MHz (Fig. 2, Table 2). The indication that beam size was important relative to a smaller role for the ultrasonic frequency was also noted by O\’Brien et al. (2001). The 7.5-MHz PCH sizes were relatively small, but not as small as might be expected from the beam diameter of 0.83 mm relative to the 3.8 mm at 1.5 MHz. For example, group A2 at 1.5 MHz and 1.2 MPa had PCH areas averaging 3.3 mm in width, whereas group B1 at 7.5 MHz and 1.3 MPa had PCH areas averaging 2.5 mm in width. The relatively larger PCH sizes for the higher frequency, in particular, may have been due to the phenomenon of lung sliding. Some regions of the lung surface moved 1 mm or more during breathing, so that the beam affected an area larger than the fixed-beam size.
The results of this study are compared with earlier fixed-beam pulsed ultrasound results from Child et al. (1990), Zachary et al. (2001) and O\’Brien et al. (2003a) in Table 4. The 1.2-MHz result of Child et al. (1990) for 10-μs pulses was about the same as our 1.5-MHz result for 10-μs pulses. However, the higher frequency of 3.7 MHz resulted in a higher threshold (than our 7.5 MHz result) and indicated a small dependence of the thresholds on ultrasonic frequency. The difference between 0.7 MPa at 1.2 MHz and 1.0 MPa at 3.7 MHz is not large for a threefold frequency increase. The uncertainties in threshold determinations, which include uncertainties in dosimetry, are typically ±10%–15% for PRPA (e.g., see Table 3). The threshold for 1-μs pulse duration was also somewhat higher than our results for relatively short pulses for the modulated exposure conditions, but not greatly different from the DUS results. These differences might result from the different species or other uncertain factors. Overall, our results and those of Child et al. (1990) 25 y ago might be considered to be in rough agreement.

br Acknowledgments We acknowledge the Natural Sciences and

We acknowledge the Natural Sciences and Engineering Research Council of Canada (NSERC) for Grants 034685 and 034813 (UBC), which supported this project. We also thank the Centre for Hip Health and Mobility for providing the lab facilities and the Institute for Computing, Information and Cognitive Systems for program support.

The flexor tendon pulley system of the finger functions to maintain the flexor Atractyloside Dipotassium Salt of the fingers close to the phalanges, enabling full range of motion in finger flexing movements (Amis and Jones 1988; Roloff et al. 2006). These structures are subjected to extreme forces in sports such as rock climbing (Bollen 1988), and their rupture is a frequent consequence. Accurate diagnosis of pulley injuries depends on the use of crucial imaging techniques, but these are often accompanied by challenges.
The most widely employed technique for visualizing the finger flexor pulley system is ultrasound, as it enables the physician to examine these structures in real time and in a dynamic fashion (Hauger et al. 2000). For a better understanding of how the pulleys are visualized using ultrasound, Figure 1 compares the anatomic structures to their respective ultrasound images. Pulleys have traditionally been difficult to visualize directly using ultrasound, causing dependence on indirect symptoms such as the distance between flexor tendons and phalanx in a flexed finger position for pulley rupture diagnosis. However, with newer ultrasound equipment offering better visualization using higher frequency probes, direct visualization of the pulleys has achieved greater significance as a diagnostic (Klauser et al. 2002). For instance, Kovacs and Bodner (2002) were able to visualize all of the annular pulleys, including A3 and A5, as well as the cruciate pulleys. Boutry et al. (2005) were able to consistently visualize the A2 and A4 pulleys, the A3 pulley in 65% of cases and the C3 pulley in 45% of cases using a 17 MHz probe, concluding that a minimum frequency of 17 MHz is necessary for the visualization of the A3 pulley. Direct visualization of the A2 and A4 pulleys has subsequently reached a high diagnostic value. However, direct visualization of the A3 pulley remains accompanied by challenges and is limited to 17 MHz probes—instruments not typically available to normal clinicians, which restricts their use in clinical studies.
As the direct visualization of the A3 pulley remains difficult and with 65% rather random, ultrasound cannot be relied on as a secure method of diagnosing ruptures of the A3 pulley or those in which the A3 pulley is a component. In a magnetic resonance imaging cadaver study using the same specimens as used in this study, Bayer et al. (2015) were able to use a new, indirect approach for diagnosing A3 pulley ruptures. They included measurements involving the volar plate (VP), and were able to show that diminished translation distances of the VP relative to the middle phalanx base, as well as augmented VP tendon distances in the crimp grip position, were suitable indirect indicators for A3 pulley rupture. So far, this approach has not been applied to ultrasound imaging.
This study thus focused on the visualization of each pulley and its location with regards to the proximal interphalangeal (PIP) joint, crucial when considering a repair (Roloff et al. Atractyloside Dipotassium Salt 2006), as well as on determining the accuracy of the ultrasound technique in determining correct pulley rupture—particularly of the A3 pulley. In order to achieve this, particular attention was paid to the visualization of the VP to determine whether the indirect approach from the magnetic resonance image could be applied to the ultrasound technique. For improved visualization, a picture enhancing technique (speckle reduction) was employed, leading to a high resolution of small structures (Wunsch et al. 2007).

Materials and Methods
All measurements were completed using a GE Logic 9 (GE Healthcare, Buckinghamshire, United Kingdom) with a linear M12 L Matrix probe, an aperture of 3.9 cm and a frequency of 14 MHz. The cross beam settings were set to “low,” and the speckle reduction was left at “2” to maintain comparability with an in vivo environment. A 14-MHz probe, readily available to every clinician, was used to ensure the relevance of these research results to the improvement of diagnostic tools in clinical settings.

br Methods br Results br Discussion Some



Some measure of the appropriateness of the effective diffusivity model can be gleaned from the data in Figure 5. The close agreement between the experimental drug concentration trace and the computational one is evidence that MDV3100 the complex phenomena underlying ultrasound-enhanced drug transport can be captured in the model with one critical parameter (porosity) and two less important parameters (thickness and delay time). Presumably, if more parameters were required or a multiscale approach was necessary, close agreement in both the pre-ultrasound and post-ultrasound regimes would not be attained. An estimate of the agreement between the experiments and computations, and hence of the appropriateness of the model, is provided by the optimization algorithm. The algorithm yields not only a best guess for the porosity, but an estimate of the RMS error between experiments and the effective diffusivity model.
The large uncertainty in the porosity ratio for an intensity of 2 W/cm2 is due to the single trial for which the ratio is 12.5. This ratio, along with the ratios for all of the other trials, are illustrated in Figure 6. Ignoring the singularly large value, the mean porosity ratio for the 2 W/cm2 intensity is 3.2, with a standard deviation of 0.8. With or without the singularly large value, a one-tailed t-test yields the conclusion that the porosity ratio is significantly larger than one (p < 0.05). The standard deviations as a percentage of the mean, ignoring the single large value, are less than 30% for the four intensities. At the higher pressures used in the study, ultrasound-induced cavitation potentially played a role in changing the porosity of the epithelial layer. Although the peak negative pressure is likely too low to initiate cavitation (mechanical index < 0.5 in all cases) within the cornea, the cornea was adjacent to a liquid mixture containing tap (non-degassed) water combined with sodium fluorescein. As reported by Atchley et al. (1988), the cavitation threshold in water at a frequency of 0.98 MHz is on the order of 400 kPa, comparable to the higher pressures in this study. (In the study of Atchley et al., the water was degassed, but contained latex particles.) Using the same model transducer as the one from our study, and a passive cavitation detector, Castellanos et al. (2017) detected noticeable energy (about 10 dB above noise level) at frequencies equal to half and 1.5 times the fundamental frequency (800 kHz), during 1 W/cm2 exposures. The presence of energy at these frequencies is a strong indicator that inertial cavitation was present. Morphologically, the increase in porosity may be due to a transient increase in intracellular spacing within the epithelial layer, caused by oscillation of cavitation-induced bubbles near the cornea surface, or to the microjets arising from the collapse of the bubbles (Paliwal and Mitragotri 2006). The small reduction in epithelial thickness is possibly due to the removal of cells from the surface layers of the MDV3100 epithelium (Zderic et al. 2004a).
Although the pressure across the corneal surface was assumed to be uniform, it was seen in Figure 2 that the pressure decreased by about a factor of 2 over the radius of the orifice. The effect of the variable pressure distribution on the variability of the porosity distribution was estimated in the following manner. Given that the pressure varies over the scale of the orifice radius, about 6 mm, and the thickness of the epithelium is less than one-hundredth of that, we assume that the pressure field is locally uniform, that is, the epithelium at any radial location responds to the pressure of the ultrasound beam at that location. To model the increase in porosity with pressure, we hypothesized a local enhancement of porosity on pressure of the formwhere p0 is the threshold pressure below which no porosity enhancement occurs. That pressure and the scaling constant b were determined by first integrating this function for LE across the entire corneal surface, to find the total enhancement TE:

From experimental findings only three wires were

From experimental findings, only three wires were taken for the central strip (not five as sketched in Fig. 2d), and only two solid back wings were required (not four as in Fig. 2d). Then the total inductance became 150nH and this fairly matches the experimental requirements.
Fig. 7 shows the experimental results as acoustic amplitudes in the piezo signal, obtained in volts as the 2MHz raw signal. The two circular pancakes behaved in a very similar manner as shown in Fig. 4. The circular R=14mm coil was slightly more powerful at g=5mm and at higher distances, as already discussed. At shorter distances, the R=8mm coil became more powerful due to the higher field density. The practical butterfly coil was not superior at small distances; it Rapalink-1 Supplier only approached the R=14mm coil. However, the butterfly became more effective at higher distances above 10mm: At g=20mm, about five times the acoustical power (=squared amplitude) was obtained experimentally than from the larger circular coil. This is a quite significant improvement and not just caused by different mode structures in the rod. Notably, distance g affected the butterfly’s signal less, as the slope was less steep. In addition, the butterfly coil produced a smaller footprint than even the smaller circular coil.
The characteristic footprint can be visualized practically with malleable aluminum foil as a target material: the magnetic pressure of a pancake prints a characteristic toroid (with a non-affected center) in the foil, similar to the diffuse rings shown in Fig. 6. The butterfly produces a linear ditch over length L, almost as if impressed by a sharp edge and naturally without a passive center. Undoubtedly, then, the acoustic beam propagation inside the target will also differ: due to diffraction [14,15], the opening angle would be smaller when parallel to the magnetic “blade” in the L-direction and higher in the perpendicular w-direction (Fig. 2d).

For somewhat lower energies (probably a more practical approach: then based on solid-state switching and suitable for high repetition frequencies) and lower field intensities, the use of ferromagnetic materials, like iron powder cores or ferrite, as back plates should be advantageous. This was already presented by Jian and Dixon [7]. As an appreciated feature, for simple induction coils as an ultrasonic transmitter and receiver, such a back plate would not interfere with the field of stationary magnets (as required in conventional EMATs).

This work is initiated and supported by the internal research founding of the University of Applied Sciences Ruhr-West. The author wishes to thank Tino Morgenstern [9] for performing the FEM crosschecking.

Ultrasound (US) guidance of HIFU beam focus has a number of advantages in comparison with the one offered by the Magnetic Resonance Imaging (MRI) that is currently used for the imaging and monitoring of thermal fields [1]. The MRI-guided HIFU technique requires ultrasonic equipment to be adapted to work in strong (several Teslas) magnetic fields and the treatment itself needs to be delivered in electromagnetically shielded operation room. These limitations, along with the need for maintenance of MRI system, make the MRI-guided HIFU arrangement bulky and relatively expensive. Hence, there is a clear need for development of an alternative, noninvasive temperature imaging and monitoring method that would be able to bypass the above mentioned limitations. In this work, the temperature field distribution was determined by processing the backscattered ultrasound signals.
In the following, the ultrasound estimation of temperature-induced changes in sound velocity of echoes backscattered from the locally heated tissue volume is presented in the context of using Homeotic genes for a priori imaging of the HIFU-induced thermal field distribution and it is shown that the two-dimensional (2D) image of these heat-induced changes in the sound velocity can be obtained to provide the calibrated 2D temperature distribution image. The implementation of this technique involves using the HIFU beam of low intensity before the commencement of the treatment and generating the ultrasound temperature distribution maps from the images of changes in the sound velocity corresponding to a low (about 2°C) temperature elevation. The thermal maps obtained predict the location and extent of the region (the so call ‘hot spot’) where the thermal lesion is expected to be formed during thermo-ablative treatment.

At the time of exploration

At the time of exploration, vaginoscopy demonstrated irregular fibrous tissue at the Phenyl sulfate and normal-appearing vaginal mucosa in the distal two-thirds of the vagina. A Pfannenstiel incision was made, and gross inspection of the pelvis did not identify any lymphadenopathy or local spread. The mass was palpable at the cervix in continuation with the proximal vagina. The left ovary was congenitally absent. The right ovary was adherent to the posterior aspect of the uterus. A right oophorectomy, total abdominal hysterectomy, and proximal vaginectomy were performed, knowing this would render the patient infertile and reliant on hormone replacement therapy. The remaining vaginal cuff was biopsied, and the frozen section was negative for malignancy. The majority of her vagina was preserved (Fig. 2C). Final pathology showed fibrous scar tissue and a nonviable focus of tumor without evidence of teratomatous elements within the uterus and right ovary (Fig. 2B). Her postoperative AFP level was 7 ng/mL.

Vaginal bleeding in young girls poses a challenge. Striegel et al recommend the routine use of examination under anesthesia, cystoscopy, and vaginoscopy to fully elucidate the etiology of vaginal bleeding. The sensitivity of diagnosis of malignancy by noninvasive imaging alone was just 33% compared with 100% with examination under anesthesia, cystoscopy, and vaginoscopy. Any young girl with vaginal bleeding must undergo further investigation, and a failure to include YSTs in the differential can lead to excessive morbidity and delayed treatment.
Cisplatin-based chemotherapy was introduced in the 1980s and has improved survival in children with GCTs at all anatomic sites. Initial management was with vincristine, actinomycin, and cyclophosphamide chemotherapy, but this has been replaced with BEP owing to less toxicity. A 2003 study by Rescorla et al identified 12 girls diagnosed with YST of the vagina with biopsy or subtotal resection followed by BEP treatment. The goal was vaginal preservation. Nine patients underwent secondary surgical resection after 4 cycles of chemotherapy for the presence of residual tumor. Three girls in the standard dose arm and no girls in the high-dose chemotherapy arm developed progressive disease or relapse over 4 years. Excellent results were seen with high-dose cisplatin. This is consistent with studies of BEP for GCTs of other sites. They reported a 2-year survival rate for vaginal GCTs of 70%. There is a paucity of data for uterine or cervical YSTs, and these are typically treated in the same manner as vaginal YSTs.
Growing teratoma syndrome is a recognized outcome after chemotherapy for GCTs. Patients with mixed GCTs with known teratomatous elements would be most likely affected by this clinical entity. In the pediatric population, mixed GCTs most commonly occur in the ovary, and growing teratoma syndrome has been described in a 4-year-old girl previously treated for ovarian mixed GCT. There are no reports of mixed GCTs arising from the vagina or uterus, although this is not unsuspected with the rarity of this entity, overall. In this particular case, there was a large tumor with only a relative percentage of it sampled via transvaginal biopsy, leaving occult mixed elements a possibility. When a complete response was not achieved with chemotherapy, the possibility of residual teratoma was entertained and should be included in the differential for residual disease in this complex and rare entity.


Urethral stricture disease can cause men to experience a host of problems including lower urinary tract symptoms, pain, and ejaculatory and bladder dysfunction. Urethral stricture disease is common and accounted for an estimated 1.2 million office visits in the United States between 2002 and 2007. Urethroplasty remains the gold standard treatment for urethral strictures. Because most published outcomes on urethroplasty is derived from individual surgeon case series, there is a lack of national level data reporting trends in the type of urethroplasty performed, patient and hospital characteristics, and perioperative outcomes and complications of urethroplasty.

As an open busy and strategically located

As an open, busy and strategically-located international port, agarwood stolen in other Asian countries is sometimes smuggled into Hong Kong to end up in the key markets in East Asia (Table 4). In May 2014, a fake fishing boat carrying 400kg of agarwood worthy of US$640,000 was intercepted by custom officers in Hong Kong\’s territorial water (Apple Daily, 2014). It was the largest confiscated consignment on record of smuggled agarwood. Such wildlife crime perpetrated in other countries and channeled through Hong Kong would impose pressure on Aquilaria survival in their countries of origin. It is necessary to get support from the International Consortium on Combating Wildlife Crime (ICCWC). Formed by the United Nations in 2011, it order DZNep deals squarely with the problem of illegal wildlife trade that has thus far escaped legal control at the international level (Nooren and Claridge, 2001; CITES, 2011). This overarching body, comprised of CITES, INTERPOL, World Bank, World Customs Organization, and United Nations Office on Drugs and Crime, would work jointly to tackle trans-national wildlife crime. It is important for Hong Kong to work with ICCWC to suppress the illicit inflow and outflow of agarwood.

Towards enhanced protection and conservation
The aggravating challenges cannot be resolved with routine measures and minimum intervention, and least of all, with insouciance. The crux of the issue departs from the situation in other source countries which aims at regulating harvesting and promoting responsible tapping methods. In Hong Kong, the objective is the pure form of nature conservation, which means zero harvest and exclusion of theft. To prevent further depletion of the valuable biotic resource, 26 actions have been proposed based on the above findings. They have been characterized under statutory, administrative, and scientific action-type tripartite, and Hong Kong, mainland-China, and international territorial-scope tripartite. Furthermore, they have been categorized according to priority and implementability (Table 5):

Agarwood theft in Hong Kong presents a host of anomalies. It involves a special administrative region of China with inherently different social, economic and political traits in comparison with its mainland parent. Hong Kong has established the administrative and legal infrastructure to implement a successful program of nature conservation. In conjunction with public education and community-wide support, natural resources including wildlife have been protected. Fundamental changes in the socioeconomic profile and outlook have almost completely abandoned primary production. For some decades, the forests have lost their economic roles and mainly serve conservation and amenity objectives. The extensive protected area system, historical cultivation of A. sinensis, and protection of fengshui woodlands associated with villages have jointly guarded the local forests against intrusion and degradation.
Thus the local countryside has maintained a healthy population of the species in comparison with forests in south China, where it has been hunted down to the threatened status. Continued planting of the species in afforestation program in Hong Kong, with recent focus on native species, has helped to sustain its population. Despite the presence of some large century-old trees, and increasing value of agarwood, theft by locals has hardly happened. The potential to yield precious agarwood, however, has attracted the attention of some criminal elements across the border in mainland China. Juxtaposition of the two domains separated by a largely porous border has facilitated people-cum-material movements and induced cross-border crimes (Lo, 2010).
With near-exhaustion of supply from the wild populations in mainland China where it has been designated as protected species, the theft has found an alternative, conveniently-located and easily-accessed stock in Hong Kong. It has literally spilled into the Hong Kong hinterland due to the pull of a relatively undisturbed tree pool. The operational spheres of the theft syndicates have expanded through the highly permeable border. The large amount of agarwood imports and re-exports in the legal-trade stream (Table 4) through Hong Kong involves products originated mainly in Southeast Asian countries, whereupon a good proportion is re-exported to mainland China, Taiwan, South Korea and Japan. The agarwood theft in Hong Kong, on the other hand, yields products that are smuggled into mainland China, where the loot in the black market would be “cleansed” to become legitimate commodities for sale within and outside the country.