br Noncontrast computed tomography NCCT is the

Noncontrast computed tomography (NCCT) is the gold standard for the evaluation of nephrolithiasis. The advantages of NCCT include superior sensitivity and specificity, the ability to identify ureteral calculi, the accurate assessment of stone size, and the ability to discover alternative pathology accounting for the clinical presentation. Despite these advantages, there is growing concern over increased cost and most importantly the cumulative risk of ionizing radiation exposure. For these reasons, recent research has been conducted to evaluate the safety of using renal ultrasound (US) as an alternative to NCCT for the evaluation of patients with suspected urolithiasis. Most notably, Smith-Bindman, in a multicenter comparative effectiveness trial, showed that the use of initial diagnostic US had no significant differences in high-risk diagnoses, with complications or serious adverse events, when compared to NCCT for patients presenting to the emergency department (ED) with renal colic.

Midurethral sling (MUS) placement is one the most common surgical procedures performed for stress urinary incontinence (SUI), with an estimated rate of 9.45 cases per 10,000 persons in 2009. The incidence of SUI is increasing as the American histamine dihydrochloride ages; it is estimated that 40% of childbearing women develop SUI and 6% experience a significant negative impact on their quality of life. The personal and societal economic costs for incontinence continue to rise as the US population ages. In fact, $12 billion are spent annually for this problem, 70% of which represent out-of-pocket costs. Given these significant consequences, it is imperative that surgical techniques are optimized and surgeons strive to minimize adverse outcomes. Furthermore, as our healthcare landscape changes, reimbursement for these procedures may be tied to readmission rates, 30-day complications, and patient-reported satisfaction in the near future.
MUS is relatively unique in that it is widely performed by physicians of different disciplines. Utilization is increasing as there is concomitant decline in traditional procedures such as Burch. In Taiwan, an estimated 17.5% of surgeries for SUI were performed by urologists, vs 81.8% by gynecologists. Similarly in Ontario, 43% of patients underwent mesh-based procedures for incontinence by urologists and 57% by gynecologists. Differences in training or technique by subspecialist may impact patient outcomes. Studies have demonstrated relationships between training and outcomes for identical procedures by pediatric surgery vs pediatric urology, or general surgery vs thoracic surgery, which may also hold true for MUS.
Complications are often not followed with adequate duration in sling trials and it has been challenging to accurately tabulate complication rates due to loss of follow-up. A recent study retrospectively evaluated the incidence of revision surgery after SUI procedures and found no differences in outcomes based on surgical specialty. However, this work studied a heterogeneous patient population by including concomitant procedures such as hysterectomy and sling revisions. Its aim was not to assess perioperative differences in outcome for only MUS. We aimed to study clinical outcomes for the MUS placement alone, defined by no concomitant procedures performed. We hypothesize that there is no difference in meaningful morbidity or mortality for MUS by surgical subspecialty, regardless of differing patient mix between groups.

Owing to their reproducible, long-term outcomes, midurethral slings (MUS) have become the most-studied surgical procedures for stress urinary incontinence (SUI). The current manuscript provides an excellent summary of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database of short-term adverse events for >8700 MUS procedures. The complication rates were low and short-term readmissions were infrequent, both findings in concert with previous studies. Although the objectives of the study were met, the current manuscript uncovers some of the shortcomings of data mining.

On cross sectional imaging these

On cross-sectional imaging, these lesions are usually solid and hypovascular. They can be associated with cysts and calcifications. On Doppler ultrasonography, the echogenicity of the lesion can vary, but there is usually little blood flow seen. Noncontrasted CT scans may show calcifications, whereas contrast-enhanced CT scans confirm the tumors to be solid and homogenous with only mild enhancement. These tumors have lower attenuation after contrast administration than does the renal parenchyma. Limited data are available on the appearance of this tumor on magnetic resonance imaging scans. In case reports, these lesions are usually hypointense on non–gadolinium-enhanced T1 and T2 imaging, and again have lower intensity signal than does the surrounding renal parenchyma, adding little to the ability to preoperatively diagnose this tumor. These imaging characteristics can be explained by the low vascularity of the tumors, which has been confirmed with angiography studies. There is only a single report of a completely cystic mass as in our case. The variable and nonspecific radiographic findings of these tumors make it difficult to distinguish MA from WT or RCC; histopathology is needed for definitive diagnosis.
Our case was a largely cystic lesion. In adults, the Bosniak classification system would give guidance as to the likelihood of malignancy and suggest therapeutic options, but this system has not been validated in children. There are no clear guidelines on how to handle complex cystic lesions in the pediatric population.
Biopsy has been advocated by some, with conflicting reports as to the success of fine needle aspiration to effectively establish an MA diagnosis, because this lesion can be very difficult to differentiate from other malignant tumors. Biopsy of unilateral tumors is not recommended under current Children\’s Oncology Group protocols as this results in tumor upstaging. Additionally, in cystic cases such as ours, the nondiagnostic rate of renal biopsy is likely to be higher than with a solid lesion. If MA is diagnosed preoperatively, consideration of observation vs surgical intervention can be discussed. Because the natural history of these tumors is largely unknown, most reports support radical or partial nephrectomy for these lesions. There have been few reports of observation for these lesions, albeit with short follow-up. The natural history of this lesion is not known as most tumors are resected on diagnosis. There is a single case report of 5 years of observation of a child with an MA, which showed exponential growth of the tumor before excision. Postresection follow-up is not well defined.
On pathologic examination, these tumors usually comprise epithelial elements arranged in tubules. The tumor, although well circumscribed, typically has a discontinuous Protease Inhibitor Library if any capsule at all. There are often associated psammoma bodies. Immunohistochemical staining is variable, although most tumors are positive for WT-1 and CD57, unlike our case, which was negative for CD57. This lesion can often be confused with an epithelial WT variant or papillary RCC. Fluorescence in situ hybridization can be useful to differentiate MA from papillary RCC, the latter generally showing chromosome 7, 17, and Y aneuploidy. Although atypical features can be present, these do not predict the risk of metastases as abnormal pathologic features have been reported in both metastatic and non-metastatic cases. Similarly, 2 cases of pediatric regional lymph node metastases were reported in patients without cytologic atypia.

Conclusion

Case Report
A 12-year-old female presented to the emergency department with worsening abdominal pain, drenching night sweats, a 10 lb weight loss over the past month, constipation, urinary urgency and incontinence, weak stream, dysmenorrhea, menorrhagia, and vaginal discharge. She was recently treated for bacterial vaginosis. The patient was otherwise healthy without medical or surgical history, significant family or social history, and was not taking medications or supplements. Her physical examination found her afebrile with stable vital signs, a palpable and firm left flank mass, and a large protruding tumor adherent to the anterior vaginal wall. The patient had normal external female genitalia and no palpable adenopathy. Laboratory evaluation demonstrated white blood count of 14.7, Hgb of 8.0, hematocrit of 26.1, platelets of 563, Cr of 0.74, albumin of 3.1, and electrolytes that were within normal range, as were her serum human chorionic gonadotropin and alfa fetoprotein. Urinalysis showed red and white blood cells, and urine culture had no growth. An abdominal ultrasound revealed a complex heterogeneous mass with hyperechoic elements measuring 25 cm in the left retroperitoneum and distinct solid homogeneous pelvic mass hypoechoic cystic components. Computed tomography scan of the chest, abdomen, and pelvic with contrast demonstrated a 23 cm heterogeneous mass involving most of the left kidney with a pseudo-claw sign and low attenuation, and a separate 10.8 cm similar-appearing heterogeneous mass in the vagina, along with extensive intra-abdominal, pelvic, and inguinal lymphadenopathy and liver and lung metastasis (Fig. 1A). A non-contrast pelvic magnetic resonance imaging further characterized 5 cystic components (2 large and 3 small) in the pelvic mass (Fig. 1B). Brain imaging and total body scan were negative. Because there was compression of the great vessels by the renal mass, the patient was placed on prophylactic enoxaparin. Image-guided biopsy of the renal mass demonstrated monophasic blastemal Wilms tumor: malignant blue cell morphology with pseudorosette structures and surrounding fibrous connective tissue positive for WT-1 in both the N-terminus and C-terminus on nuclear staining (Fig. 2). Examination under anesthesia and vaginal biopsy confirmed diagnosis of a metastatic Wilms tumor deposit (Fig. 3) as this lesion did not communicate with the primary renal lesion.

br Comment In our series using standardized

Comment
In our series, using standardized validated questionnaires as the MSHQ-EjD-SF, we observed that ejaculatory dysfunction is a highly prevalent condition in men with LUTS/BPE (119/220 = 54%). As reported by previous series, age, LUTS, and ED are strong predictors of ejaculatory dysfunction. More specifically, in our experience, age and lower IIEF score were found to be predictors of anejaculation, moderate/severe decrease in ejaculation force, and moderate/severe decrease in ejaculation volume, whereas only higher IPSS score was found to be a predictor of moderate/severe decrease in ejaculation force. The current results are in line with the available evidence and confirm the internal validity of our results. Even though previous studies have investigated the role of different cardiovascular risk factors on ejaculatory dysfunction, to our knowledge, this aconitine is the first available evidence on the role of MetS on ejaculatory dysfunction. However, disregarding the presence of a theoretical pathophysiological mechanism behind this association, according to our results, MetS could not be considered as a risk factor for EjD.
On the other side, we confirm the role of MetS as a risk factor for ED. Several studies have focused on the role of MetS in ED. Corona et al evaluated 803 patients with sexual dysfunction and found that patients with MetS presented worse erectile function. Moreover, Heidler et al investigated MetS as an independent risk factor for ED in 2371 men from 30 to 69 years old. In their experience, patients more than 50 years old with MetS had a 49% higher risk for ED. Chen et al confirmed the aforementioned results in a Chinese cohort. Their findings show a 34% higher risk of ED for patients with MetS. Finally, the recent meta-analysis from Liu et al evaluated 10 studies on MetS and ED, concluding that men with MetS when compared with the reference group experienced a significantly increased risk of developing ED (relative ratio: 1.60, 95% CI: 1.27-2.02; P = .001); however substantial heterogeneity was observed (I2:  92.9%; P = .001). In our experience, patients with MetS have twice the risk of having ED (odds ratio [OR]: 2.24, 95% CI: 1.081-4.648; P = .030) when compared with patients without MetS.
Likewise, the relationship between ED and LUTS has been extensively evaluated in the past years. Large epidemiologic studies and subsequent meta-analysis all over the world have confirmed a close relationship between LUTS and ED, with OR ranging from 1.5 to 8 depending on the cohort. However, in our series, LUTS could not be considered as a risk factor for ED. Probably, this result can be easily explained by the low median IPSS present in our population (median IPSS = 7) due to the exclusion of all the patients on BPH/LUTS medication. In fact, looking more closely to the available evidence, the association clearly depends on the severity of the symptoms. Ponholzer et al, in their large epidemiologic study including over 2000 patients, evaluated the association between LUTS and ED in a population of men ranging from 20 to 80 years. The association was present in the majority of the cases; however, comparing patients (between 61 and 70 years) with IPSS <7 with patients with IPSS >7, the presence of LUTS could not be considered as a risk factor for ED (OR: +1.37, 95% CI: 0.7-2.6). Although our study confirms the well-known relationship between age, LUTS, and ED, we failed to show a direct association between MetS defined according to the Adult Treatment Panel III criteria and EjD evaluated using MSH-EjD-SF. To our knowledge, this is the first study evaluating the role of MetS on EjD using standardized criteria to define the presence of the syndrome as well as validated questionnaires; therefore, our results could not be compared with similar experiences. The only data available in the literature is the association between different cardiovascular risk factors as hypertension and EjD, which was also confirmed in our study (data not shown). However, as already stated in different studies evaluating the relationship between MetS and urologic diseases, it has been suggested that evaluating the single components of the syndrome may confound or obscure a comprehensive assessment of the patient metabolic status. Considering that what we know is only the tip of a very large iceberg, further studies should better investigate the pathophysiological mechanisms involved in EjD in patients with LUTS and BPE to better manage these patients.

br Conflicts of interest br Sources

Conflicts of interest

Sources of funding

Introduction
The treatment of upper third ureteral stone is common in daily urological practice. Extracorporeal shock wave lithotripsy, ureteroscopic lithotripsy, and percutaneous nephrolithotomy are the recommended therapeutic modalities for upper third ureteral stones refractory to medical expulsive therapy. The outcomes vary according to the size of the stone, degree of obstruction, duration of the symptoms, and the experience of the surgeons. Ureteroscopic lithotripsy with ultrasonic, electrohydraulic, pneumatic, and laser lithotripters has evolved steadily in the past 20 years, resulting in decreased morbidity and better outcomes. Pneumatic lithotripsy uses vibrating mechanical force to break the stone. It may have a lower risk of ureteral perforation when compared with laser lithotripsy, but it is associated with a higher rate of stone pushback into the renal pelvis. A previous study revealed the stone-free rate varied according to stone size. We therefore compared these two modalities for the treatment of upper third ureteral stones, and focused on the effect of stone size on treatment outcomes.

Materials and methods
Patients who underwent ureteroscopic lithotripsy for upper third ureteral stone by pneumatic lithotripter or holium:yttrium–aluminum-garnet (Ho:YAG) laser between 2012 and 2013 were retrospectively reviewed. Patients with urinary tract infection, radiolucent stone, loss of follow-up, concurrent middle or lower third ureteral stone, or acute renal failure were excluded from the study. The stone size and burden were evaluated by computerized tomography and/or plain radiography of kidney–ureter–bladder. The size was defined as the longest diameter of the stone. The sum of the stone sizes was used if there were more than one stone. The stone burden was defined as the area of the stone calculated by our imaging system after the stone was delineated (Figure 1). Follow-up kidney–ureter–bladder or computerized tomography was performed 1 month after ureteroscopic lithotripsy. Stone upward tachykinin receptor was defined as a stone fragment > 3 mm pushed back into the kidney visible on radiography. The stone-free rate was defined as no residual stones > 3 mm within the urinary tract 1 month postoperatively.

Operative technique

Statistical analyses
The Student t test and Chi-square test were used for comparison between pneumatic and laser lithotripsy groups. A p value < 0.05 was regarded as statistically significant.
Discussion
Two decades ago, difficult access to the proximal ureter by large and rigid ureteroscopes made extracorporeal shock wave lithotripsy the first-line treatment modality for upper third ureteral stones. Improvements in ureteroscope design (semirigid and small diameter scopes) have resulted in better outcomes. The two most commonly used ureteroscopic modalities for stone disintegration are pneumatic and laser lithotripsy.
The mechanism of pneumatic lithotripsy is similar to that of a pneumatic jackhammer, with the pushing force on the stone leading to more likelihood of stone upward migration. Laser lithotripsy decomposes stones by a photothermal mechanism and causes less oscillation of targeted stones. These different mechanisms affect the stone-free and upward migration rates. Many studies have shown that laser tachykinin receptor lithotripsy has a better stone-free rate. Results of our study are in agreement with those of these reports. Perez Castro et al reported median stone-free rates of 84% and 81% for stones < 10 mm and > 10 mm, respectively. The lower stone-free rates in our study can be explained by our stricter definition of stone-free (stone fragments < 3mm in size), and by the fact that most of the procedures were performed by residents during their training. In our setting, the diameter of laser fiber was 600 μm and the energy setting was 1.2–1.6 J. Several studies had revealed that larger fiber and higher energy settings causing more stone upward migration. This could explain the high upward migration rate in this study. In this study, a large percentage (62.7 %) of procedures for stones > 10 mm resulted in stones being pushed back into the kidney during pneumatic lithotripsy. A higher rate of stone upward migration was seen for larger stones in the pneumatic group but not in the laser group. Our results are in agreement with those of a comparative study by Garg et al, which also reported a higher stone upward migration rate in the pneumatic group than in the laser group. We therefore recommend the use of laser lithotripsy for upper third ureteral stones > 10 mm. Pneumatic lithotripsy is associated with a higher rate of stone pushback. The retropulsion rate was reported in 2–17% of ureteral stone treatments and was related to an inability to trap a ureteral stone in a capacious ureter. Ways to prevent stone retropulsion include placing the patient in reverse Trendelenburg position, decreasing water pressure, and the use of stone trapping or ureteral occluding devices. Delvecchio et al reported the use of a 0.8-mm pneumatic lithotripsy probe placed through a 4.8-Fr hollow LithoVac (Taipei, Taiwan) suction probe. The suction device prevented stone migration and helped maintain a clear endoscopic view.

Interestingly Freedland et al reported that obese men who underwent

Interestingly, Freedland et al. [14] reported that obese men who underwent open RP were twice as likely to experience a capsular incision during the RP (vs. nonobese patients), which was associated with a higher risk of positive margins after the RP. Similar results have been observed among patients who underwent laparoscopic RP [15]. However, this buy TAPI-1 study failed to identify a significant difference in the RP specimens with positive surgical margins according to the BMI groups. Thus, these findings suggest that the possible prognostic value of obesity may not be associated with positive surgical margins that are the result of technical challenges during the surgery.
Although the associations of BMI with established characteristics are interesting, the association with a more definitive end point (e.g., BCR) is more likely to improve clinical decision-making regarding adjuvant therapy and follow-up scheduling. Therefore, we evaluated the association of BMI with BCR after RP and found that both overweight and obese status independently predicted BCR. Our findings corroborate the results of previous studies, which revealed that higher BMI values independently predicted BCR after RP [11,13,16,17]. In addition, a recent meta-analysis evaluated 26 studies with various designs (pooled population: 1.3 million patients who underwent RP for PCa) and revealed that obesity was associated with an increased risk of BCR (probability range: 12%–20%) [18]. However, other studies have failed to detect a significant correlation between obesity and BCR [15,19–22]. The differences may be related to variations in case mix and treatment selection, as bias toward selecting low-risk patients was present in many studies [7]. Furthermore, although BCR was not correlated with BMI-based obesity, BCR was independently predicted by waist circumference and visceral adipose tissue (detected using computed tomography) [21]. Fewer data support the association between obesity and other end points such as metastatic progression or cancer-specific survival. Chalfin et al. [23] recently demonstrated in a cohort of 11,152 men who underwent RP at a single institution that male obesity defined as a BMI to less than 35kg/m2 was associated with cancer-specific survival.
Several biochemical mechanisms have been proposed to explain the association of obesity with the biological behavior of PCa. One explanation is that overweight patients express different levels of various exocrine and paracrine mediators (vs. patients with normal weight), such as cancer-modulating estrogens, testosterone, insulin, and insulin-like growth factor and its binding proteins [24]. Furthermore, obesity is associated with increased expression of inflammatory biomarkers, such as interleukin-6 and tumor-necrosis factor α, which are involved in PCa tumorigenesis and aggressiveness [24,25]. Moreover, obesity-related changes in the levels of leptin and adiponectin may be responsible for more aggressive tumor biology [26]. Moreover, gene expression signatures that are associated with elevated BMI at the RP exhibit correlations with altered levels of lipid metabolism. In this context, statin treatment can affect BCR, which supposedly occurs through the targeting of SCD1 (among other BMI-related proteins) [25].
In this study, the addition of BMI status to the established prognostic models did not improve their accuracy by a clinically significant margin. The question of whether obesity status improves the ability in clinical practice to predict cancer outcome requires further statistical analysis such as the C-index definition. This limits its use in clinical decision-making regarding adjuvant therapy or follow-up scheduling or both. Therefore, it may be more promising to pursue markers that reflect the biological processes that are associated with adipose tissue׳s effect on tumor cells (e.g., estrogen, testosterone, leptin, adiponectin, or insulin derivatives).

Conclusion

Ethical standards

br Acknowledgements We thank all of the volunteers who participated

Acknowledgements
We thank all of the volunteers who participated in this nationwide survey; without their help, this large-scale work would not have been possible. AL was funded by the Academy of Finland (grant 275606). Ministry of Environment has supported winter bird censuses in Finland. The language usage in this article was checked by the Wiley Editing Service.

Introduction/background
Between 1950 and 2014, the percentage of the world’s population classified as urban dwelling increased from 30% to 54% (UN, 2014). Urbanization has many documented adverse effects, including an increase in order oxycodone hydrochloride consumption, the deterioration of living environment (Konopacki and Akbari, 2002), an increase in ozone levels (Rosenfeld et al., 1998), and warmer urban streams (Somers et al., 2013; Nelson and Palmer, 2007; Hathaway et al., 2016). Further, More extreme heat waves are likely in city centers and are expected to increase due to climate change (Gao et al., 2012; Luber and McGeehin, 2008), under which extreme heat events are anticipated to become more recurrent and longer lasting in the next century (Meehl and Tebaldi, 2004). Thus, determining how to live in urban environments in a sustainable manner that promotes public and ecological health is critical.
A well-documented phenomenon that occurs due to urbanization is the urban heat island (UHI) (Oke, 1982). This effect is characterized by warmer daytime and nighttime temperatures in a city compared to its surrounding areas. It is more pronounced in larger cities with dense urban development and sparse vegetation (Mallick and Rahman, 2012). The greatest difference in temperature typically takes place overnight, with the urban area producing a higher daily minimum temperature (Tmin) and therefore a lower diurnal temperature range (DTR) (Oke, 1982; Arnfield, 2003), that is, the difference between the daily maximum temperature (Tmax) and Tmin). Higher Tmax is primarily caused by the low albedo (Taha, 1997; Giridharan et al., 2004), or low reflected light, and a lack of vegetation, which leads to lower evapotranspiration rates (Taha, 1997; Shukla and Mintz, 1982; Grimmond and Oke, 1999).
The study of urban microclimates and their relationship to land cover and population characteristics has become more prevalent over the past ten to fifteen years (Stabler et al., 2005; Harlan et al., 2006; Hart and Sailor, 2009; Ellis et al., 2017). Studies have analyzed the correlation between the UHI and other characteristics of an urban environment, including: vegetation (Linden, 2011), population density and night light (Linden et al., 2015), percentage of impermeable surfaces (Linden et al., 2015; Hass et al., 2016), the spatial pattern of greenspace (Li et al., 2013; Connors et al., 2013), and various land use/land cover features (Hart and Sailor, 2009). Since tree canopy cover (Hart and Sailor, 2009) and built/paved surface coverage (Connors et al., 2013; Linden et al., 2015) have shown the greatest effect on temperature variation, these two land cover characteristics, in addition to the distance of an area from the city center, are chosen herein for further analysis.
Within the context of vegetative contributions to temperature mitigation, planting and/or protecting existing vegetation, which adds shade and evapotransporative cooling, is a promising technique being considered to reduce urban heat and falls within the increasingly promoted use of green infrastructure in urban environments. Studies have shown that urban parks (i.e., singular, large green spaces) have a cooling effect on surrounding areas (Chang et al., 2006; Doick et al., 2014; Ca et al., 1998). However, the effectiveness of parks may also vary by individual park characteristics (Chang et al., 2006). Thus, the interactions between vegetation and surrounding land uses, the density of green space, and other factors may produce a patchwork of climates, or microclimates, within an urban setting (Stabler et al., 2005). There is a critical need to understand these interactions to develop mitigation strategies and support sustainable development using strategically placed green infrastructure.

Indicators of UHI intensities differ in all

Indicators of UHI intensities differ in all these studies, potentially leading to divergent results. Kastendeuch et al. (2000) proposed measuring the UHI intensity of the Strasbourg agglomeration by selecting the temperatures simulated at Place Kléber (48°35′00″N and 7°44′45″E) as representative of the dense urban core, and the simulated temperatures of the synoptic meteorological station of Entzheim (48°33′N and 7°38′E) as representative of the rural hinterland. We applied this method to our simulated data and found an average nocturnal UHI intensity for August 2010 (between 10p.m. and 6a.m.) of +3.08°C for the initial case while Kastendeuch et al. (2000) found a nocturnal UHI intensity of +4°C for 1 and 2 August 2002. Nevertheless, those scholars underlined that the urban-recorded 2m screen-level air temperatures reflected more specific local surface conditions inherent in the geographic location of the meteorological station or grid than the true amplitude of the UHI. Thus, it seems preferable to adopt another way to measure UHI intensity. Cantat (2004) suggested using a dense network of urban and rural meteorological stations to assess the UHI intensities of the Paris agglomeration (France, 2845km2, 10.6 million inhabitants). Debbage and Shepherd (2015) proposed assessing UHI intensity by defining urban and rural temperatures as the average of the minimum daily temperatures of all urban grid LY2109761 of a simulation domain, and of all rural grid cells included in a 50-km radius around the built areas, respectively. Finally, Lemonsu et al. (2015) took urban temperatures to be the temperature of the atmospheric grid cells included in the city center, and rural temperatures the spatial average temperatures of all the non-urban grid cells located on the boundaries of the simulation domain. This method can provide adequate indicators when focusing on less dense urbanized zones characterized by a macrocephalic urban configuration (i.e. the existence of a single highly dominant urban pole in an urban region). The calculated rural temperature may then provide a background temperature, a fortiori because the meteorological forcing data of the parent domain are provided laterally. We have used this method to calculate the extreme UHI intensities for our scenario. We modify slightly the index by choosing the urban temperature as the maximum temperature in all the urban grid cells included in Strasbourg city center. Although UHI intensities were higher, the difference between the scenarios remains low. A similar output is obtained in the paper of Lemonsu et al. (2015), which deals with the impacts of the urban change dynamics on the urban heat island of Paris megacity by 2100. Consequently, it is possible that the city-wide UHI saturates until a given city size, which questions the interpretation of the well-established relationship between the city size and the UHI intensity (Oke, 1973). Besides, the method of Lemonsu et al. (2015) is questionable for densely urbanized zones or national frontier zones where large secondary built centers may be located on the boundaries of the simulation domain, and modify the rural temperatures. Our research therefore suggests that further work is required to devise relevant indexes for describing the impact of development policies on the UHI effect. The UHI intensity indexes are average measurements that describe a whole study area. Temporally, such monthly averages may hide possible peaks of the UHI intensity at specific points in time; spatially, differentiations also may exist (Zhang et al., 2009; Lemonsu et al., 2015). Indeed, Fig. 11 shows local increases of the air temperatures, whose value and locations are very different between the two simulated scenarios. The more numerous local increases of the air temperatures that characterize the moderately compact scenario do not impact the UHI intensity because the places of temperature increases are mainly located at the periphery of the urban area in 2010. The question now is whether this result could be interpreted positively in favor of a moderately compact urban development, knowing that the simulated population is higher for this scenario. Besides, the compact scenario creates numerous infilling developments in Strasbourg city center from which result no temperature increases. The key question that arises now is whether the absence of temperature increases reveals a limit of the WRF/urban climate system or a real preservation of a good ventilation of the city center that avoids local increases of the air temperatures. Actually, further researches are required to answer those questions.

br Introduction Medical imaging plays a

Introduction
Medical imaging plays a major role in the clinic. Currently, several established technologies are available for imaging. However, there is an ever-increasing need to broaden the spectrum of imaging capabilities. This may be achieved by seeking new technologies using new physical phenomena suitable for imaging, or by creating hybrid systems from existing modalities or by mapping new tissue properties that have not previously been imaged. Current imaging modalities map attenuation coefficients (X-rays and computed tomography [CT]), magnetic relaxation properties (magnetic resonance imaging [MRI]), acoustic scattering (ultrasound), metabolic rate (positron emission tomography), perfusion (single-photon emission CT) and more. Nevertheless, to the best of our judgment, very little attention has been paid to the thermal properties of the tissue (e.g., thermal conductivity, k, and thermal diffusivity constant, K) as a EAI045 source.
Another motivation related to this study is non-invasive surgery using high-intensity focused ultrasound (HIFU). With the HIFU technique, a special ultrasound transducer is used to generate a virtual acoustic “knife” to ablate non-invasively a small volume of tissue within the body. HIFU non-invasive surgery has become very popular in the past few years. Image-guided HIFU surgery has recently been offered as a non-invasive alternative to conventional lumpectomy in several organs, and it may be considered the surgical knife of the future (Kennedy et al. 2003).
The major mechanism in HIFU non-invasive surgery is currently thermal ablation. Consequently, much attention has been focused on temperature mapping for the purpose of image-guided surgery, particularly by MRI (e.g., Gianfelice et al. 2003; Huber et al. 2001; Hynynen et al. 2001; McDannold et al. 2010; Madersbacher et al. 2000; Tempany et al. 2003; Wu et al. 2002). However, temperature mapping is not the only important feature in monitoring thermal ablation. Thermal diffusivity and perfusion at the ablation site also play an important role in the final therapeutic outcome. Hence, mapping the thermal diffusivity at and around the target site, before and during treatment, may potentially optimize the procedure.
Moreover, as reported by Lagendijk et al. (1988), for example, tissue thermal diffusivity is different in tumors as compared with normal tissue. Tumors generally have higher and more variable perfusion (Song 1983), and their vasculature has a poorer response mechanism to stress than that of a normal tissue (Emami and Song 1984). This may be the reason for the differences in thermal properties. On the basis of these differences, it may also be possible to differentiate tumors from normal tissues and perhaps to differentiate between malignant and benign tumors. Thus, the development of a non-invasive method for measuring tissue thermal diffusivity could be valuable in the diagnosis of tumors as well. This may be beneficial in the diagnosis of breast cancer, for example.
Imaging techniques for thermal diffusivity and perfusion measurements using MRI have been reported (Cheng and Plewes 2002). However, very few studies have attempted to measure these parameters by ultrasound (Anand and Kaczkowski 2008). An “all-ultrasound” thermal estimation technique is a more attractive option to use with therapy and diagnostic systems, because the cost and operating expenses of the MRI scanning system are very high, and it has a lower temporal resolution compared with ultrasound imaging. Additionally, access to the patient within the MRI scanner is quite limited, and the sensitivity of the scanner to radiofrequency energy imposes severe restrictions on the use of additional medical equipment, when needed.
In this study, using the concept of an ultrasonic CT-guided HIFU system, as suggested in Azhari (2012), we describe a method for evaluating the thermal diffusivity of a tissue directly from speed-of-sound (SOS) profiles. The SOS profiles were obtained by TT ultrasonic imaging during cooling of the tissue after it was heated by HIFU.

Autophagy Compound Library However nearly all nanobubbles or microbubbles in previous studies were

However, nearly all nanobubbles or microbubbles in previous studies were prepared based on DSPE-PEG2000 polymer chain which only can carry one FOL residue at a time, because it has only one carboxyl terminal. Suppose one DSPE-PEG2000 chain could carry two or more FOL molecules, the targeted nanobubbles maybe more effective in selectively targeting FR-positive tumor cells. Therefore, to further improve the selective targeting ability of nanobubbles, a novel targeted nanobubble ((FOL)2-NB) with two FOL molecules per DSPE-PEG2000 chain was synthesized. Increasing FOL content per DSPE-PEG2000 chain was accomplished with the help of L-2-aminoadipic Autophagy Compound Library (AD), as illustrated in Fig. 1.
On the basis of these considerations, the aims of this study were: (i) to prepare twofold FOL targeted nanobubble ((FOL)2-NB), and (ii) to investigate the selective targeting ability of (FOL)2-NBs to FR-positive tumor cells in vitro. The bubble size and distribution range were measured by DLS method. Enhanced imaging ability was evaluated using a custom-made agarose mold with a clinical US imaging system at mechanical indices of up to 0.12 at a center frequency of 9.0MHz. Targeted ability was also carried out in human breast cancer MCF-7 cells, which over-express the FR, by fluorescence activated cell sorting (FACS) and fluorescence microscopy, respectively. To properly study the activity of (FOL)2-NBs, analogous carboxyl-terminated nanobubble (Non-targeted-NB) without FOL incorporation and Autophagy Compound Library another targeted nanobubble (FOL-NB) with one FOL molecule per DSPE-PEG2000 chain were studied as control.

Materials and methods

Results

Discussion
With the development of nanotechnology, nanobubbles with various shells (phospholipids, polymers or protein) and cores (gas, liquid, or solid) have increasing attracted more attention in ultrasound molecular imaging and tumor theranostic [23]. Although EPR effect is a remarkable characteristic of nanobubble in tumor tissues, the exploitation of this feature alone might not be sufficient to reach a successful cancer treatment. FR-targeted nanobubble integrated the advantages of both EPR effect and tumor selective targeted treatment, and can enhance the therapy effect of chemotherapeutic drugs or genes for FR positive tumors, and meanwhile decreasing side effects.
There are two different strategies for targeting FR, a monoclonal antibody against FR (e.g. mAb Mov18 [24,25]) or FOL itself [26–28], properly linked to a drug delivery system. When these two approaches were compared, FOL showed some advantages than mAb Mov18, such as low immunogenicity [29], high stability, commercially available at low cost and without relevant side effects [29–31]. Based on these considerations, the aims of this study were mainly directed toward designing and implementing a novel FOL targeted nanobubble with increasing FOL content (accomplished by linking two FOL molecules per DSPE-PEG2000 chain), and understanding the targeted ability of it by specific cell membrane receptors of FR. For our purpose, the FOL residues were conjugated to the dendron of derivatives DSPE-PEG2000-AD-(COOH)2 (B) which allowed twofold FOL content payloads.
Lipid-coated nanobubbles with no, one or two FOL molecules per DSPE-PEG2000 chain were therefore prepared, and their biological behavior at cellular level was evaluated. In particular, our research focused on follows: (i) development of (FOL)2-NB, (ii) detection of cytotoxicity to cells, (iii) analysis of the physical properties and its contrast-enhancing ability, and (iv) evaluation of tumor cell targeted ability. To properly evaluate (FOL)2-NB, analogous carboxyl-terminated nanobubble (Non-targeted-NB) without FOL residue incorporation and another targeted nanobubble (FOL-NB) with one FOL molecule per DSPE-PEG2000 chain were also developed as control. The selective linkage of FOL to the same polymer chain was achieved by employing a DSPE-PEG2000 [32]. AD was used as branching unit for the synthesis of a small dendron at DSPE-PEG2000 end [33]. This strategy, as illustrated in Fig. 1, enabled to link two FOL molecules per DSPE-PEG2000 chain with a good yield. The synthetic route was designed to couple FOL as last moiety to avoid partially activation and coupling of –COOH group of FOL, which is essential for the interaction with its receptor [13]. 1H NMR of DSPE-PEG2000-AD-(FOL)2 confirmed that this polymer was successfully synthesized, as shown in Fig. 3.