br Methods br Results br Discussion Investigators



Investigators have examined the contribution of low socioeconomic status to the incidence of prostate cancer in AA men [26,27], but there is a paucity of work that characterizes the unique interaction between income inequality and hiv protease inhibitor regarding the delivery of treatment to these men who need it most. In this retrospective cohort study of 102,486 AA and non-Hispanic white men with localized high-risk prostate cancer, AA men were 49% less likely than white men to receive definitive therapy for prostate cancer after adjusting for patient demographics, comorbidity, and cancer prognostic factors. Moreover, this hiv protease inhibitor racial disparity in receipt of definitive therapy widened significantly among low-income men. Although high-income AA men were 40% less likely than high-income white men to receive definitive therapy, the treatment disparity expanded to 51%—even more striking—among low-income men.
Although the analyses adjust for regional education, urban/rural residence, and income, it is possible that some of the census-tract-level data does not capture patient-level characteristics that influence patient and provider decisions. Recent work demonstrates significant lack of comprehension of common prostate cancer terms [28] and barriers to shared decision making [29] among economically disadvantaged men. Poor communication between patients and providers regarding the efficacy and adverse effects of treatment likely encourages decisional regret among some AA men [30] and contributes to the prevalence of shared perspectives for or against certain health care interventions within communities. Patient refusal of recommended surgery or radiation is correlated with increased prostate cancer mortality [31], and it is probable that disproportionately fewer recommendations for primary therapy to AA men likewise contribute to less receipt of therapy and greater prostate cancer mortality.
Although affordable care is a critical component to improving treatment access and outcomes for low-income men, providers must also work to address other factors that limit the quality of care delivered to vulnerable populations, such as communication, transportation, and access to high-volume hospitals [32,33]. Although this study did not evaluate insurance status, Mahal et al. [22] show that the racial disparity in receipt of primary therapy between AA men and white men narrows with access to insurance, though large socioeconomic treatment disparities continue to exist even in nations with universal health care [34].


Conflict of interest/disclosures

When the World Health Organization (WHO) published its 2004 guidelines for classification of urothelial carcinoma (UC) and chose to recognize distinct variant histology (VH), one of its aims was increasing identification of these variants on pathology specimens [1]. Better understanding of these VH forms of UC leads to greater knowledge of prognosis and treatment strategies specific to individual variants. Despite initial descriptions of variants more than 20 years ago, molecular pathways for the divergent development of specific VH within primary urothelial bladder carcinoma have not been elucidated [2,3]. Divergent differentiation is poorly understood; although, Cheng et al. [4] have suggested sarcomatoid urothelial cancer developing as the final common pathway in UC differentiation. The true prevalence of VH has likely not increased over the past decade, although this is difficult to prove retrospectively [5]. Rather, increased pathologic awareness of the possible morphologic variants is likely the driver of increased variant diagnosis.

Using an institutional database, we conducted a retrospective review of all patients who underwent radical cystectomy for UC of the bladder at our institution between 2008 and June 2013 (n = 698). As the current WHO guidelines recommend that patients with any component of small cell histology be managed as primary small cell carcinoma, we eliminated all patients with small cell variant (n = 22). Patients with locoregional metastatic disease that underwent cystectomy after preoperative chemotherapy or with a history of management under a bladder-preservation protocol were excluded (n = 52). Dedicated genitourinary pathologists assigned all UC VH using centralized pathology review, which included regular review of all malignant histology and variant classification to ensure standardization within the group. Outside hospital transurethral resection (TUR) specimens underwent VH reassignment by this same group of genitourinary pathologists. Histologic descriptions of VH are available from prior studies [2].

Titus et al reported similar findings

Titus et al. [21] reported similar findings comparing T and DHT levels in 18 men with CRPC to 18 men with BPH without prior hormonal treatment. Tissue testosterone levels in each group were similar, prostate cancer (1.09ng/g tissue) and BPH (0.8ng/g tissue). However, tissue DHT levels were 91% lower in recurrent prostate cancer (0.36ng/g tissue) compared with BPH (3.98ng/g tissue; P < 0.001).

Radical prostatectomy is an established option for the definitive treatment of clinically significant prostate cancer. Despite the adequate oncologic control and low complication rates achieved with the current surgical approaches, a percentage of patients is faced with disease recurrence, usually manifesting first as detectable serum prostate-specific antigen (PSA) levels. Accurate identification of the source of a rising PSA in the postprostatectomy setting is currently a major challenge among the urologic oncology community. Current guidelines recommend the consideration of salvage radiotherapy (SRT) to the prostate bed in patients with biochemical recurrence after prostatectomy [1–3]. Several reports have found that SRT is more effective in achieving durable PSA suppression when treating patients with lower PSA levels, and thus SRT is being increasingly administered to patients with the initial manifestation of a rising detectable PSA [4]. Despite this, the likelihood of maintaining an undetectable PSA at 2 years after such treatment is often less than 40%, especially among high-risk patients with elevated Gleason scores [5,6]. A number of factors may contribute to the failure of SRT, one of which is the presence of undetected metastatic sites of disease outside of the pelvic buy VER155008 treatment field.
Conventional imaging modalities for the detection of postprostatectomy recurrence include magnetic resonance imaging (MRI), bone scintigraphy (BS), computed tomography (CT), and positron-emission tomography (PET). A combination of these is typically applied, and there are many reports documenting the use of these techniques, in particular MRI, for the detection of recurrent disease [7–13]. However, all of these studies include patients with relatively high PSA levels, although some do document less optimal performance in patients with lower PSA values. It is clear that better techniques for disease localization in patients with early PSA rise are desirable, and several experimental approaches are undergoing initial evaluation for use in this context. Before implementing new strategies, better understanding of the baseline scenario with the current standard of care tools is necessary for benchmarking. To date, no studies have reported on the use of conventional imaging specifically for the assessment of early postprostatectomy PSA rise. Thus, the purpose of this study was to assess the positivity rates of imaging examinations performed in patients with early PSA rise (≤1.0ng/ml) after radical prostatectomy (RP); and to summarize the management strategies (e.g., biopsies and treatments) adopted in parallel with imaging in this patient population.


The median PSA at the time of imaging was 0.21ng/ml (interquartile range: 0.15–0.36ng/ml). There was a significant association between higher PSA levels and positive imaging findings (Odds ratio: 26.6 [95% CI: 3.1–230.6]; P = 0.0029) (Fig. 1). Radical prostatectomy Gleason score was 3+3 in 8 patients; 3+4 in 53 patients; 4+3 in 51 patients;≥4+4 in 28 patients; and not available in 2 patients. There was extracapsular extension at prostatectomy in 99/142 patients and seminal vesicle invasion in 28/142 patients. The median interval between RP and imaging was 933 days (range: 59–5,572 days).
All 142 patients underwent at least 1 imaging examination. Pelvic MRI was performed in all patients; and was positive in 15/142 (11%) patients (in 14 patients it showed local recurrence in the prostatectomy bed and in 1 patient it showed a pelvic osseous metastasis [Fig. 2]). None of these patients had abnormal lymph nodes on pelvic MRI. The median PSA of patients with positive pelvic MRI findings was 0.18ng/ml (range: 0.07–0.9); and their median time from prostatectomy to imaging was 983 days (range: 152–4,288 days). Prostatectomy Gleason score was 3+4 in 6/15 patients, 4+3 in 6/15 patients, ≥4+4 in 2/15 patients, and unknown in 1/15 patient. A total of 13/15 patients had extracapsular extension; 5/15 patients had buy VER155008 seminal vesicle invasion, and 7/15 patients had positive surgical margins on the RP specimen. Of these 15, 10 patients underwent additional imaging examinations; none revealed local recurrence in the prostatectomy bed or additional positive findings. Prostatectomy bed biopsy was performed in 5 of the 14 patients with local disease identified on MRI; pathologic evaluation was positive for recurrence in 4/5 of these patients. Of the 15 patients with positive imaging findings on pelvic MRI, 12 received treatment (3/12 received salvage radiation, 8/12 received combined salvage radiation and androgen deprivation therapy, and 1 received systemic chemotherapy), 1 patient declined treatment, in 1 patient salvage radiation was considered, but withheld because of toxicity risk in view of coexisting inflammatory bowel disease; and 1 patient was lost to follow-up.

In the m buffer the beta coefficient of sky view

In the 40m buffer, the beta coefficient of sky view factor is −0.167 which expresses the weaker impact of this parameter compared to tree volume in this radius. In the next step, the mean value of SVF in different buffer radii is used to investigate the variation of SVF impact and the total R2 of the regression model using different buffer distances. The buffer radius for tree volume is fixed to 40m in these calculations. The results are presented in Table 5.
Fig. 11 presents the comparison between tree volume and SVF standardized beta coefficient for different buffer radii.
The influence of sky view factor on UHI increases with increasing the buffer radii. In smaller buffer zones, this parameter is not significant while in larger buffer zones it is significant. This behaviour is opposed to the behaviour of tree volume which has higher impact on smaller cisapride and lower effects on the larger zones. This indicates that the impact of tree volume is larger at local scales than sky view cisapride factor. Choosing 40m as the buffer radius in which trees have the most influence on UHI, the regression is expressed as Eq. (1):where TVTotal is the total tree volume (in m3) within 40m buffer and SVFMean is the SVF mean value within 30m buffer. Concerning the R2, this model explains 44.3% of the variation of UHI. The remaining variation derives from unaccounted factors. One of these factors could be proximity to water, and since Amsterdam is characterized by interwoven water bodies, its temperature can be significantly influenced by water. However, we assume that around sunset, in a low wind condition, water does not have a direct impact on UHI due to water switching role from heat sink to heat source. While during the day water bodies (e.g. city lakes) act as cooling element and cool down the environment, at night the opposite occurs. During the night, the air temperature is lower than the water temperature and therefore water bodies warm their surroundings. This leads to temperature increase in the proximity of water at night (Theeuwes et al., 2013). This has been acknowledged for the specific case of Amsterdam where water did not present consistent impact on the nocturnal temperature (Koomen and Diogo, 2015).
Fig. 12 presents the generated UHI map using the developed regression model (Eq. (5)).
These results suggest that if a planner/designer wishes to mitigate one degree of UHI, he would need to account with extra 60,000m3 tree volume in 40m buffer zone (according to Eq. (5)). In order to calculate on average how many trees (of which category) are needed to realise this volume, we need to take into consideration the geometrical characteristics of trees in the study area (Table 2). The approximate required number trees of each tree class to fulfil 60,000m3 tree volume in 40m buffer is 90 small trees or 20 medium trees or 4 large trees (see Table 6).

Discussion and conclusion
This research focused on exploring the impact of local trees on nocturnal urban heat island intensity of Amsterdam. It is acknowledged that trees mitigate UHI due to shading and transpiration. Both processes are related to the 3D aspect of trees and should be taken into account in such UHI investigations (Armson et al., 2012). In this study we have applied tree volumes derived from a 3D tree dataset of Amsterdam. To uncover the maximum local impact of trees on UHI, we have defined buffers with varying radii around each air temperature observation and aggregated the volume of trees inside the buffer. For each buffer radius, the impact of the aggregated tree volume on the UHI has been estimated using multi-linear regression analysis. Sky view factor, as another local parameter, and urbanization degree, as a regional parameter, were taken into account for each observation point as additional explanatory variables, next to tree volume, in the regression model.
Applying the regression for each buffer zone, the buffer radius in which tree volume impact is highest, was chosen as the local distance to which tree groups yield the highest influence on the local UHI. Results of this research show that the impact of tree volume is maximum on the smallest buffer radius of 40m. The regression model suggests that for the characteristics of the studied day, around 90 smaller trees or 20 medium trees or 4 large trees in 40m buffer zone of a location could lead to one degree decrease on its UHI.

The key research challenge is optimizing UGS delivery in

The key research challenge sigma receptor optimizing UGS delivery in the compact city context (Burton et al., 1996; Gordon and Richardson, 1997; Burton, 2000) regarding limitations and solutions. The findings could be applied to other compact cities as well as less compact ones in which the densely-packed old cores are amenable to rejuvenation, gentrification or renewal (Thörn, 2012). Besides, the findings can inform cities undergoing densification to achieve urban revitalization (Lehmann, 2010; Haaland and Konijnendijk van den Bosch, 2015). In the infilling process, UGS supply could be sustained to address livability and quality-of-life concerns (Kyttä et al., 2013; Schmidt-Thomé et al., 2013). In consolidating the urban form, the natural and recreational qualities of UGS should not be compromised (Arnberger, 2012). The experience and plight faced by the high-density Hong Kong could offer object lessons and precautions against UGS deficit in the course of development.

Study approach
This study was based on a literature review of government documents and published articles mainly spanning from the 1980s to 2015 focus on existing status and policies. Relevant official publications in the public domain were consulted by using the keywords of the 25 greenspace issues (Fig. 2) to search for sections to read. Useful data were harvested from printed data books with the help of the table of contents or index, or from government websites using the built-in search functions. Large-scale maps, zoning plans and aerial photographs furnished additional spatial information. The study was supplemented by field evaluations of UGS sites selected based on the greenspace categories (local, district and regional) with samples taken from old urban core and new towns, first-hand experience in town planning in Hong Kong as a member of the statutory Town Planning Board for eight years, and three decades of research on urban forestry and greening in the city. The paper is organized into three discussion sections with 25 subsections summarized in a synoptic chart (Fig. 2).
UGS standards of selected cities, and extensive research findings, policies and practices reported in the literature specific to the respective constraints, have been enlisted for comparison and as the basis for recommendations to improve delivery quantity and quality. With suggestions based on data, findings of other studies and existing body of knowledge in urban forestry and urban greening, the advocacy pitfall could be avoided. Four innovative solutions catering to the unique circumstances of Hong Kong (Table 2) are worthy of pilot testing to evaluate feasibility and to allow refinement of implementation logistics.
Public open space (POS), the official term equivalent to UGS, is prescribed by the Hong Kong Planning Standards and Guidelines (Fig. 3), which is promulgated by the Town Planning Board and implemented by the Planning Department (2007a) through the legal instrument of Outline Zoning Plans (OZP). The statutory basis of governance is embodied in the Town Planning Ordinance (Justice Department, 1997). The minimal private open space provision is regulated by a different administrative setup tropical rain forest biome is peripheral to the mainstream planning mechanism.
Information on POS was gleaned from government reports and research papers, namely Tian et al. (2011), Audit Commission Hong Kong (2013, 2014b), Census and Statistics Department (2014), Hong Kong Council of Social Services (2014) and Hong Kong Housing Authority (2014). China’s national UGS standards and guidelines (State Department, 2001) serve as a reference as most Chinese cities are compact. UGS planning standards used in other compact cities such as Singapore (Urban Redevelopment Authority, 2014), Malaysia (Federal Department of Town and Country Planning Peninsula Malaysia, 2006), and Europe (data summarized by Baycan-Levent and Nijkamp, 2009), were used for comparison.

Hitherto, urban planning and development in Hong Kong have neglected preserving and creating nature within the urban fabric. In the process, high-order natural enclaves have been eliminated or degraded. The city has incurred a notable ecological debt or nature deficit, with undesirable effect on people and nature. The poor emulation of nature in urban parks, dominated by manicured and regimented vegetation and artificial surfaces, cannot substitute for high-quality nature. Creating inter-site connectivity with peri-urban natural ecosystems can link isolated and dispersed green pockets to form a UGS network to complement the built-up matrix.

rad51 inhibitor br The end of the Fairmount Park Commission

The end of the Fairmount Park Commission
In the first decade of the 21st century, press releases, newspaper editorials, and government reports began to articulate a new knowledge of the urban park. These efforts increasingly framed the park as a tool for economic development, a vital component of the economic fabric of the entrepreneurial city, even as they drew heavily from the differentiation of the park from the city that ecological restoration efforts promoted. However, this new vision no longer framed the park as a bucolic site for re-attuning oneself to nature\’s rhythms or preserving the non-human world. Rather, it was framed as a financial asset, one that could contribute to the city\’s economic rad51 inhibitor by becoming financially self-supporting and “reap[ing] dividends” from the services it provides (Shields, 2008). In short, the park was being leveraged an integral part of the urban economic fabric rather than an exceptional space outside of it.
This position was first clearly articulated in the Fairmount Park Commission\’s 2004 strategic plan for the park system, called “A Bridge to the Future”. Then-mayor John Street\’s introduction to that plan, in which the old idea of the park as wild space is clearly discernible, describes the park as a “place of adventure and exploration … of quiet contemplation and hidden beauty” (Fairmount Park Commission, 1999). Images that accompany the report reflect this vision, including the cover image, taken in Wissahickon park, the most heavily-wooded of the seven watershed parks, in which nine out of ten acres were declared “natural lands” by NLREEP. The image captures demonstrates at once Street\’s vision of the grandeur and the human scale of its historical structures (Fairmount Park Commission, 2004, pg 4).
At the same time, following Street\’s introductory statements, the report\’s primary authors argue that the original, nineteenth-century-era goals of the park system had been achieved: open space had been secured, forests preserved, water resources protected. A new challenge faced the park commission, they argued, required a reconfiguration of park land governance and the recalibration of park commission goals so that they were more in line with the needs of a different kind of city. The park\’s problems at that time, the report argued, resulted from “years of financial hardship and decline” and a lack of “philosophical approach to reach its full revenue-generating potential” (Fairmount Park Commission, 2004, pg 3).
In response, park commissioner Robert N. C. Nix III and Park Commission vice president Alex Bonavitacola issued comments that argued that the park commission\’s problems stemmed not from the fact that the commission lacked vision or competence, but because it had been underfunded for decades. Indeed, according to one independent report, the Fairmount Park system was one of the worst funded park systems in the nation (Philadelphia Parks Alliance, 2007). For the next four years, a succession of competing reports from various organizations appeared, each envisioning a different future for the park system, each marshaling a different body of evidence to support its view of how the park ought to be governed. In the process of articulating these seemingly divergent stances, old visions of the park were being dismantled and a new park began to emerge.
In March, 2006, less than a year after Clarke\’s and Reynolds’ bill was introduced, the Philadelphia Parks Alliance, the dominant park advocacy group in Philadelphia, articulated its own vision of the future of parks, detailed in a report entitled “Better Parks for a Better City” (Philadelphia Parks Alliance, 2006). The report presented findings from a public opinion study, and was widely accepted as an accurate representation of both the desires of the city\’s populace and as a fair description of the park and its value.

The study also showed that

The study also showed, that the bigger the tree, the longer the distance required to reduce the observed intrusion events. This result can be explained by the fact that bigger trees have a higher capacity to laterally extend their roots to reach water and nutrients. Bogotá’s planting authority should avoid planting tree species from the Ficus, Salix, and Prunus genera in the proximity of urban infrastructures. Pohls et al., 2004 and Stål (1998) have also identified these genera as highly intrusive. All species identified as responsible for causing tree intrusion events share the characteristics of fast-growing, strength and longevity. Except for the specie Phoenix canariensis Chabaud, these species share root system special features: medium or high depth and high root strength. The species Phoenix canariensis Chabaud belongs to the palm family Arecaceae, and have not been identified as an intrusive tree in previous studies. More CCTV videos and field information are required to verify this finding.

Vegetation is of particular interest as it presents a versatile resource for effectively managing and moderating a variety of problems associated with urbanization. Urban vegetation serves a multitude of urban dihydrofolate reductase inhibitor functions (Bolund and Hunhammar, 1999). As a main characteristic which is the expression of the seasonal cycles of plant processes and their connections to climate change (temperature and precipitation), vegetation phenology is increasingly significant for a variety of scientific applications nowadays. The timing of phenological events can be used to document and evaluate the effects of climate change on both individual plant species and vegetation communities (IPCC, 2007). To study the features of urban vegetation phenology can better understand the ecological status of the city, the occurrence time of urban vegetation phenology can reflect the response of urban vegetation ecosystem to urban temperature change and precipitation.
Remote sensing provides a great opportunity to understand the vegetation phenology in different resolutions. The product of moderate-resolution imaging spectroradiometer Normalized Difference Vegetation Index (MODIS NDVI) time series data is one of the most popular data source (Zhang et al., 2003). The initial use of MODIS NDVI time series in monitoring global vegetation phenology was carried out (Reed et al., 1994; Moulin et al., 1997; Zhang et al., 2003), followed by increasingly number of applications at regional area (Hird et al., 2009; Shuai et al., 2013; Ma et al., 2013a,b; Jeganathan et al., 2014; Hilker et al., 2015) or global scale (Reed et al., 1994; Moulin et al., 1997; Brown et al., 2012). GIMMS NDVI is another similar data set that is widely used to detect the trend change of vegetation (Peng et al., 2012; Forkel et al., 2013; Jamali et al., 2015; Detsch et al., 2016). Relative to coarser spatial resolution data sources such as MODIS and GIMMS, Landsat series are able to resolve much greater fine-scale geographic variability in phenology (Melaas et al., 2013). Wulder et al. (2009) concluded that Landsat TM and its successive ETM+ have spatial (30m), spectral and radiometric qualities that are especially well suited for ecological characterization.TM and ETM+ data have been systematically acquired for many portions of the globe since the launch of Landsat 5 in 1984, and thus a rich archive is available for analysis (Vogelmann et al., 2012). Therefore, some researchers paid attention to application Landsat data to phenology study (Fisher et al., 2006; Vogelmann et al., 2012; Melaas et al., 2013).
Despite the great advance, few studies have been carried out in urban area. The main challenging is that the urban vegetation is different from the natural forest, which is smaller in spatial scale and more complex in spatial pattern. Phenological features of urban vegetation cannot be fully captured by aforementioned satellites (Pan et al., 2015). Fortunately, the new generation of satellite in a form of constellation, e.g. Europe’s Sentinel-2, China’s HJ-1A/B and GF-1/6, can provide more frequent observations (<1week) with a higher spatial resolution (<30m). The high spatio-temporal time-series NDVI products derived from these missions is expected to provide a great opportunity for urban applications.

Results from other animal experiments provide definite evidence of the

Results from other animal experiments provide definite evidence of the crucial role of cytokines in the onset and maintenance of pain (Milligan et al. 2003; Thacker et al. 2007). Despite the evidence, our studies indicate that increased TNF-α and IL-6 levels are similar with CCI-induced neuropathic pain. Although the mechanisms of action of pro-inflammatory cytokines involved in the regulation of CCI-evoked neuropathic pain remain uncertain, it is believed that TNF-α is present in the mast cells and Schwann cells of the sciatic nerve on the nerve-injured side of CCI rats (Hayashi et al. 2008). Ultrasound can be considered a mechanical stress inductor. Clearly, TU stimulated production of the angiogenesis-related cytokines IL-8 and basic fibroblast growth factor during the angiogenesis and soft tissue healing processes (Reher et al. 1999). From our observations, it is apparent that TU decreases sciatic nerve levels of pro-inflammatory cytokines in CCI rats. Moreover, it had been found that administration of pro-inflammatory cytokine inhibitors and anti-inflammatory cytokines attenuates neuropathic pain (Arruda et al. 2000; Schafers and Sommer 2007).
Because TU has a thermal effect, it has been extensively used therapeutically for a variety of conditions (Bierman 1954; Cambier et al. 2001; Lehmann et al. 1966). For instance, an increase of 2°C to 3°C (moderate operate heating) not only increases blood flow, but also decreases pain, chronic inflammation and muscle spasm (Baker and Bell 1991; Draper et al. 1995; Lehmann et al. 1967). The biophysical effects of ultrasound are traditionally divided into non-thermal and thermal effects (ter Haar 1999). Generally speaking, non-thermal effects are due to acoustic streaming, microstreaming and cavitation, whereas thermal effects derive from the Lomustine cost of sound waves (Baker et al. 2001). We cannot simply state that this effect may occur at any time and that physical therapy may be graded as either non-thermal (pulsed mode) or thermal (continuous wave exposure) (Baker et al. 2001). In fact, the two effects are not separable. Indeed, it is rarely true that one class of effects may be ignored completely (Baker et al. 2001; Page et al. 2013; ter Haar 1999). In this study, we did not know the temperature change at or near the site during treatment. However, it has been reported that the increased in temperature of the culture medium ranged from 0.0°C at 0.1 W/cm2 to 1.8°C at 2.0 W/cm2 after 5 min of pulsed ultrasound (Reher et al. 1997).
It has been presumed that SP creates nociceptive sensitization after incisions in mouse paws (Sahbaie et al. 2009). In this study, we noticed that CCI rats exhibited a significant increase in sciatic nerve levels of SP and NK-1R accompanied by development of increased plantar responsiveness to heat and mechanical stimuli. This finding helps to explain why SP reduced withdrawal latency and the NK-1R antagonist RP67580 increased it in CCI rats (Yoshimura and Yonehara 2006). In fact, we also observed that TU prevented the increased expression of SP and NK-1R in rat sciatic nerve after CCI. Our study was not able to explain whether the improvement in responses to thermal and mechanical stimuli occurred, because ultrasound stimulated changes in SP and NK-1R expression. Moreover, it is possible that a lack of SP could reduce the intensity of the inflammatory reaction, which thereby provides a second mechanism for decreased thermal and mechanical sensitization (Sahbaie et al. 2009).

We found that TU has anti-allodynic and anti-hyperalgesic effects in rats with neuropathic pain after CCI. Our data imply that these anti-allodynic and anti-hyperalgesic effects of ultrasound may involve the suppression of NK-1R, substance P, TNF-α and IL-6. Thus, the study reinforces the fact that TU, as a simple, tolerable and non-invasive technique, could have a great potential in the treatment of neuropathic pain, and further investigation (i.e., local temperature and higher intensities) in this area is required.

The inferior performance of the conventional method in

The inferior performance of the conventional method in this study may, at least in part, be the result of an excessive decay of the retained bubbles from a relatively long wait time (20 min 10 s), by which time freely circulating bubbles cleared from the blood pool in all animals (i.e., when bubble signals in the LV cavity became undetectable). Such a wait time was longer than those employed by others (range = 2–15 min, most frequently 4 or 10 min in mice [Bachawal et al. 2013; Kaufmann et al. 2007a; Leong-Poi et al. 2003; Sorace et al. 2012; Wei et al. 2014]) for the following reasons: (i) we used a higher bubble dose (1 × 108 bubbles) than did most investigators (range = 8–1,000 × 105, most frequently 0.1–1 × 107 or 5 × 107 bubbles in mice [Andonian et al. 2009; Bachawal et al. 2013; Korpanty et al. 2007; Sorace et al. 2012; Wei et al. 2014]), to allow both methods to detect the wide range of Esel c-kit inhibitor levels in the LPS mouse model; (ii) rapid bubble destruction followed by subtraction of the freely circulating bubble signal (allowing a shorter wait time, frequently employed by others using the conventional method) was not used because it would preclude direct comparison against the novel method in the same animal, and furthermore, the method has its own limitations (see Introduction); and (iii) differences in the experimental setup may have influenced the freely circulating bubble half-life (e.g., imaging settings/protocol, host and bubble factors).
This study indicated that for the retained bubbles, the higher its maximum concentration (Ar), the longer its half-life (ln 2/λr). The Ar vs. λr relationship was non-linear. As far as we know, this is the first in vivo demonstration of the “bubble–bubble protection” phenomenon previously described in vitro for bubbles attached to a surface (Klibanov et al. 1998). The shorter distance between neighbouring retained bubbles at higher concentrations may result in (i) increased acoustical interactions between adjacent bubbles causing mechanical responses such that the net diffusion of gas out of the bubble population is reduced; and/or (ii) reduced concentration gradients for gas diffusion out of the bubbles because of increased gas saturation in the micro-environment surrounding them. Our demonstration of such a phenomenon in vivo highlighted a potential weakness of the conventional acoustic quantification method; that is, by the time of signal sampling, the retained bubbles would have decreased by a different number of half-lives amongst subjects with different levels of target molecule expression. One consequence of this is the underestimation (or even missed detection) of targeted molecules in subjects with lower expression levels (lower maximum retained bubble concentrations), as shown in R20. In contrast, the novel method takes into account the retained bubble half-life, allowing a more sensitive and accurate quantification of the targeted molecule, as shown in Ar. This is important because the expression of targeted molecules may vary and be relatively low in natural/human disease states.
The concentration of retained microbubbles on a target tissue increases over the course of circulating bubble passage up to a point near the beginning of the elimination phase (e.g., ≈2 min post-bubble administration) (Yeh 2010). It is not clear how accurately one can determine the zero time for the retained bubble concentration decay. The same problem arises for the circulating microbubble concentration as well. For consistency, the zero time was arbitrarily taken as the time of bubble administration, giving the maximum limit for Ar and Af.
The linear acoustic range in vivo was assumed to be 0–5 AU, approximated from a limited titration experiment in vitro applying the same ultrasound settings and similar imaging c-kit inhibitor depths as for in vivo imaging (see Supplemental Fig. A1). It should be noted that this range can change for different ultrasound settings, imaging depths, tissues and bubbles.

melanocortin 1 receptor br Methods br Results Information


Information for the 45 patients, including gender, duration of transplantation and donor status, is provided in Table 1. There were statistically significant differences in GFR and duration of transplantation among the four groups (all p < 0.01). There was no significant difference in RI among the four groups (p = 0.997). The difference in corticomedullary strain was significant in all paired groups (all p < 0.005) (Fig. 4). However, the difference in inter-lobar artery RI was not significant in any paired group (all p > 0.05). There were no significant differences in EDV or PSV between groups 1 and 2 or between groups 3 and group 4 (p > 0.05) in the initial statistical analysis of the four groups. We combined groups 1 and 2 to form a new group with low-grade (≤25%) cortical IF/TA and groups 3 and 4 to form a new group with high-grade (>26%) cortical IF/TA, and then used two independent t-tests to examine the differences in EDV (Fig. 5) and PSV (Fig. 6) between the two new groups.
The differences in EDV and PSV between ≤25% and >26% renal cortical IF/TA were significantly significant (p < 0.001). An inverse correlation was found between corticomedullary strain and grade of cortical IF/TA (odds ratio = −6.097, 95% confidence interval: −9.119 to −3.075, p < 0.001) with the logistic ordinal regression test, whereas the correlation between cortical fibrosis and EDV (odds ratio = −0.203, 95% confidence interval: −0.699 to 0.294, p = 0.424) or PSV (odds ratio = 0.083, 95% confidence interval: −0.091 to 0.257, p = 0.351) was not significant. In addition, there was a moderate positive correlation between duration of transplantation and grade of renal allograft cortical IF/TA (r2 = 0.67, p = 0.00000045). Corticomedullary strain, EDV and PSV significantly differed between recipients with a GFR >60 and those melanocortin 1 receptor with a GFR <60 (all p < 0.001), whereas RI did not (p = 0.75) (Table 2). The areas under the ROC curve for the use of corticomedullary strain, EDV, PSV, RI and duration of transplantation to determine >26% renal allograft cortical IF/TA were 0.99, 0.94, 0.88, 0.52 and 0.92, respectively (Table 3, Figs. 7 and 8). The difference in diagnostic performance between two ROC curves was significant (p < 0.05). For testing intra- and inter-observer variability, Pearson\'s correlation coefficient was R2 = 0.95, and the intra-class correlation coefficient was 0.91 (p = 0.000).
The pathogenesis of IF/TA is complex, and the prevention, diagnosis and treatment of IF/TA require more sensitive non-invasive measures and multidisciplinary approaches to melanocortin 1 receptor influence the pathologic changes in the allograft (Li and Yang 2009; Nankivell et al. 2004). Our results indicate that cortical biomechanical properties measured by ultrasound strain are closely correlated with Banff grade cortical fibrosis. However, renal allograft hemodynamic status as assessed by Doppler velocity is correlated only with high-grade and lower-grade cortical fibrosis.
Improving non-invasive tools, such as the imaging techniques discussed here, to detect and measure IF/TA may result in improved care. This non-invasively acquired information has the potential to improve our decision making on biopsies in the management of our patients. In particular, our data support the hypothesis that the progression of cortical IF/TA results in both a decrease in blood flow measured by intra-renal Doppler velocity and an increase in cortical tissue hardness assessed by corticomedullary strain, which may provide more non-invasive measurements that are related to the degree of pathologic damage manifested as cortical IF/TA. Importantly, our study found that corticomedullary strain has high repeatability (R2 = 0.95) and reproducibility (R2 = 0.91) in the assessment of renal allograft cortical IF/TA.
Although our patient population was modest in size, it is interesting that our results are consistent with the concept that renal cortical strain determined by ultrasound may be closely linked to mechanical changes that result in decreased compliance as more fibrotic tissue develops in the cortex. The more compliant the tissue is, the greater is the deformation or “strain” that will develop as a result of palpation or compression. Our data in this study support this hypothesis that fibrotic tissue directly contribute to a decrease in cortical elasticity, because the deformation in the cortex under manual external compression is measurable as the degree of corticomedullary strain and related inversely to the degree of IF/TA in kidney biopsy pathology (odds ratio = −6.097, p = 0.000). With 1.6 as the best cutoff value, the sensitivity and specificity of corticomedullary strain in determining >26% renal allograft cortical IF/TA were 100% and 90% (Table 3), respectively. Because progression of IF/TA is often related to allograft function and the length of time a recipient has had a transplant, it is reasonable to expect decreases in corticomedullary strain and allograft function with increasing duration of transplantation. As we found in our study population, there was a moderate positive correlation between duration of transplantation and severity of renal allograft cortical IF/TA (r2 = 0.67) (Fig. 9). With 29 mo as the optimal cutoff value, the sensitivity and specificity of duration of transplantation in determining >26% cortical IF/TA were 90% and 63%, respectively (Table 3).

br Methods br Results br Discussion Li et al performed



Li et al. (2013) performed a meta-analysis to summarize the diagnostic performance of SWE in the differentiation of breast lesions, yielding summary sensitivities and specificities of 0.91 and 0.82 for SSI and 0.89 and 0.91 for ARFI, respectively. Unfortunately, only a total of 9 studies, including 1888 women and 2000 breast lesions, were analyzed. Moreover, the combined results of SWE and conventional US were not evaluated in that meta-analysis. We found that SWE is a feasible tool to differentiate malignant from benign breast lesions, providing quantitative information of stiffness. Moreover, our results suggest that the addition of SWE to conventional US would increase both the sensitivity and specificity. SWE is deemed a potential improvement to conventional US in the differentiation of breast lesions; it may be valuable to introduce SWE into routine clinical practice.
The studies in our meta-analysis encompassed two of the SWE modes, ARFI and SSI. Although the physical principles underlying these two elastographic techniques differ physical (Bamber et al. 2013), they are both based on shear wave propagation in soft tissues, which is induced by an ultrasound-generated THZ1 Hydrochloride force focus. Moreover, the factor of different techniques was not a significant cause of between-study heterogeneity according to meta-regression analysis. In fact, these two techniques were comparable in diagnostic performance in the differentiation of breast lesions in the subgroup analysis. Compared with ARFI, SSI improved sensitivity with a reduction in specificity, which was consistent with the meta-analysis results of Li et al. (2013). Therefore, these two SWE techniques were included in our meta-analysis. Further studies providing patient-based comparisons between SSI and ARFI are required to explain why SSI has a higher sensitivity and a lower specificity than ARFI.
Substantial heterogeneity was observed in the present meta-analysis. Theoretically, heterogeneity in meta-analyses may result from the search strategy and eligibility criteria used for inclusion, exposure constructs and outcome measures assessed, statistical methods employed and subgroup assessment (Genkinger and Terry 2014). Therefore, there are many explanations for the substantial heterogeneity in the meta-analysis. To date, no consensus of diagnostic criteria has been reached for SWE. Various elasticity measurements, such as shear wave velocity, shear wave velocity ratio, mean elasticity value, maximum elasticity value, minimum elasticity value, and ratio of elasticity value ratio, with different cutoff values are used. In addition, previous studies have found that the diagnostic performance of SWE is correlated with breast lesion size (Yao et al. 2014). SWE had a relatively low sensitivity in breast lesions <10 mm (Sadigh et al. 2013; Yao et al. 2014). Moreover, differences may exist in the breast cancers of Asian and non-Asian women, such as difference in stiffness, although further pathologic confirmation is needed. Nevertheless, all of these could not explain the heterogeneity between the studies.

Cystic fibrosis is the most widespread autosomal recessive disease among Caucasians. It is caused by a mutation in the cystic fibrosis transmembrane regulator (CFTR) gene, which codes for an anion channel expressed in epithelial cells throughout the body (Gadsby et al. 2006).
Cystic fibrosis–related liver disease (CFLD) has a cumulative incidence of 27%–35% (Colombo et al. 2002; Lindblad et al. 1999). Most cases are detected in the first decade of life (Lindblad et al. 1999). Five to ten percent will develop multi-lobular cirrhosis, leading to portal hypertension and related complications (Debray et al. 1999; Gooding et al. 2005). As a result, CFLD remains the third-leading cause of cystic fibrosis (CF) mortality (Parisi et al. 2013). Synthetic failure, however, is rare and develops slowly over the years (Gooding et al. 2005).