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There has been a large focus on the genetics of traits involved in adaptation, but knowledge of the environmental variables leading to adaptive changes is surprisingly poor. Combined use of environmental data with morphological and genomic data should allow us to understand the extent to which patterns of phenotypic and genetic diversity within a species can be explained by the structure of the environment. Here, we analyse the variation of populations of three‐spined stickleback from 27 freshwater lakes on North Uist, Scotland, that vary greatly in their environment, to understand how environmental and genetic constraints contribute to phenotypic divergence. We collected 35 individuals per population and 30 abiotic and biotic environmental parameters to characterize variation across lakes and analyse phenotype–environment associations. Additionally, we used RAD sequencing to estimate the genetic relationships among a subset of these populations. We found a large amount of phenotypic variation among populations, most prominently in armour and spine traits. Despite large variation in the abiotic environment, namely in ion composition, depth and dissolved organic Carbon, more phenotypic variation was explained by the biotic variables (presence of predators and density of predator and competitors), than by associated abiotic variables. Genetic structure among populations was partly geographic, with closer populations being more similar. Altogether, our results suggest that differences in body shape among stickleback populations are the result of both canalized genetic and plastic responses to environmental factors, which shape fish morphology in a predictable direction regardless of their genetic starting point.

The aim of the study is to report surgical and early functional outcomes of first 100 patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD) in a single center. The main surgeon (A.P.) attended a modular training program at a referring center mentored by a worldwide-recognized robotic surgeon (P.W.). The program consisted of: (a) 10 h of theoretical lessons; (b) video session (c) step-by-step in vivo modular training. Each procedure was performed as taught, without any technique variation. Demographics, intra-operative data and post-operative complications, along with early functional outcomes, were recorded for each patient. We retrospectively evaluated the first consecutive 100 patients submitted to RARC with totally ICUD from July 2015 to December 2018. Median age at surgery was 69 years (IQR 60–74). 52 (52%), 32 (32%), and 17 (17%) patients received orthotopic neobladder, ileal conduit and uretero-cutaneostomy, respectively. Median operative time was 410 min. A median number of lymph nodes retrieved were 27 and median estimated blood loss was 240 mL with median hospitalization time of 7 days. All procedures were completed successfully without open conversion. A statistically significant improvement was found in the late (30–90 post-operative days) post-operative complications (p = 0.02) and operative time for urinary derivation. At multivariate logistic regression model ASA score ≥ 3 (OR = 4.2, p = 0.002) and number of lymph nodes retrieved (OR = 1.16, p = 0.02) were found to be predictors of 90-day complications. An adequate modular training is paramount to obtain successful results and reduce the learning curve of RARC, as demonstrated by our experience.

Pubic bone osteomyelitis is a rare infectious condition which is characterized by a complex diagnostic and therapeutic workup, due to its various clinical manifestations. Among the many causes of this condition, urinary fistula is the most common in case of previous urological procedures. In order to solve this complication, it is crucial to treat both the fistula and (moreover) the infectious locus arising from it, because treating the fistula alone does not provide any control on the infectious noxa. We present the first case of pubic bone osteomyelitis arising from a urinary fistula after a robotic radical cystectomy with intra corporeal continent neobladder, which has been successfully treated through a multidisciplinary approach.

We discovered 2.8 s pulsations in the X-ray emission of the ultraluminous X-ray source (ULX) M51 ULX-7 within the UNSEeN project, which was designed to hunt for new pulsating ULXs (PULXs) with XMM-Newton. The pulse shape is sinusoidal and large variations of its amplitude were observed even within single exposures (pulsed fraction from less than 5% to 20%). M51 ULX-7 is a variable source, generally observed at an X-ray luminosity between $10^{39}$ and $10^{40}$ erg s$^{-1}$, located in the outskirts of the spiral galaxy M51a at a distance of 8.6 Mpc. According to our analysis, the X-ray pulsar orbits in a 2-d binary with a projected semi-major axis $a_\mathrm{X} \sin i \simeq$ 28 lt-s. For a neutron star (NS) of 1.4 $M_{\odot}$, this implies a lower limit on the companion mass of 8 $M_{\odot}$, placing the system hosting M51 ULX-7 in the high-mass X-ray binary class. The barycentric pulse period decreased by $\simeq$0.4 ms in the 31 d spanned by our May -- June 2018 observations, corresponding to a spin-up rate $\dot{P} \simeq -1.5\times10^{-10}\text{s s}^{-1}$. In an archival 2005 XMM-Newton exposure, we measured a spin period of $\sim$3.3 s, indicating a secular spin-up of $\dot{P}_{\mathrm{sec}}\simeq -10^{-9}\text{ s s}^{-1}$, a value in the range of other known PULXs. Our findings suggest that the system consists of an OB giant and a moderately magnetic (dipole field component in the range $10^{12}$ G $\lesssim B_{\mathrm{dip}}\lesssim 10^{13}$G) accreting NS with weakly beamed emission ($1/12\lesssim b\lesssim1/4$)., Comment: Accepted for publication in The Astrophysical Journal

Background: The treatment options for male lower urinary tract symptoms (LUTS) widely range from self-monitoring to oral medications to surgical procedures. As far as concerns surgical treatment of obstructive LUTS, transurethral incision of the prostate is considered as the gold standard in patients with mild benign prostatic enlargement. Objectives: The aim of our study is to describe this novel approach to perform ejaculation sparing Holmium laser bladder neck incision (ES-HoBNI), with particular regard to its effect on ejaculation and LUTS relief. Methods: We evaluated prospective clinical data from 143 consecutive patients who underwent ES-HoBNI at our institution from January 2012 to February 2018. Procedures were performed with a continuous flow 26 Ch resectoscope and a 550 µm holmium laser end-fire fiber. The stenotic bladder neck was deeply incised at 3 and 9’o clock down to the prostatic capsule in a retrograde direction to either side in front of the veromontanum. Results: Median Qmax, postvoid residual volume, International Prostate Symptom Score, and quality of life were 9 mL/s (7.4–10.2), 130 mL (100–190), 15 (13–19), and 3 (2–4), respectively. In total, 110 (76.9) reported regular anterograde ejaculation. Median operative time was 20 min (15–26). Median catheterization time and hospital stay were 3 days (3–4) and 22 h (20–24), respectively. Moreover, we have compared the frequency of anterograde ejaculation, which slightly increases after ES-HoBNI (77 vs. 81.2%) when compared to baseline data, despite not reaching statistical significancy. Conclusions: ES-HoBNI is a safe, reproducible technique to relieve obstructive LUTS in men with small prostates while preserving ejaculation in younger and sexually active individuals.

Objectives: To evaluate the detection rate of prostate cancer (PCa) in patients who underwent to “in bore” Magnetic Resonance Imaging -guided prostate (MRI-GB) biopsy compared to the standard transrectal ultrasound guided prostate biopsy (TRUS-GB). Materials and methods: Between January 2017 and March 2015 a cohort of 39 consecutive patients was prospectively enrolled. All the patients underwent an "in-bore" guided MRI prostatic biopsy and subsequently ultrasound-guided standard prostate biopsy. Results: Median age of patients was 65.5 years (SD ± 6.6), median total PSA serum level was 6.6 ng/ml (SD ± 4.1), median prostate total volume was 51.1 cc (SD ± 26.7). Thirty of 39 (76.9%) were biopsy-naïve patients while 7/39 (17.9%) had at least one previous negative random TRUS-GB; 2/39 (5.1%) patients were already diagnosed as PCa and were on active surveillance. In 18/39 (53.8%) men Pca was diagnosed; as regards the MRI-GB results related to the PI-RADS score, biopsies of PIRADS 3 lesions were positive in 5/18 cases (27.8%), while the number of positive cases of PI-RADS 4 and 5 lesions was 7/11 (63.6%) and 6/10 (60%)respectively. At the histological examination, 4/39 (10.3%) had a PCa ISUP grade group 1, 11/39 (28.2%) had a ISUP 2, 6/39(15.4%) had a ISUP grade group 3 and 2/39 (5.1%) had a ISUP 4-5. Conclusions: MRI-GB represents a promising technique that may offer some of advantages compared to standard systematic TRUSGB. Our preliminary experience in MRI-GB resulted safe and feasible and represents a viable procedure for the diagnosis and characterization of PCa.

Introduction: Purpose of the study was to investigate the correlation of a preoperative multiparametric magnetic resonance imaging of the prostate (mpMRI) in patients with a suspicion of prostate cancer and eligible for Holmium Laser Enucleation of the Prostate (HoLEP). Material and methods: Data of 228 patients who had undergone HoLEP was selected and retrospectively analyzed from a multicentric database. All patients presented with a raised serum PSA and/or an abnormal digital rectal examination (DRE). Prostate cancer (PCa) was excluded either with a negative mpMRI (group 'NEGATIVE MRI' n = 113) or a standard biopsy (group 'NO MRI' n = 115). Preoperative characteristic surgical and histological outcomes were confronted. A univariate and multivariate logistic regression model was performed to investigate independent predictors of incidental Prostate Cancer (iPCa). Results: Both groups presented with no statistical differences in preoperative characteristics besides previous acute urinary retention rates and post-voided residual volume, found to be higher (27.8% vs. 14.2% and median 120cc vs. 80cc) in NO MRI and NEGATIVE MRI respectively.No differences were registered in surgical time, removed tissue, catheterization time, hospital stay and complications rate.Statistically lower rate of iPCa (p = 0.03) was detected in the NEGATIVE MRI group (6.2%) in comparison with NO MRI group (14.8%). In multivariate logistic regression only presence of a preoperative negative mpMRI correlated (p = 0.04) as an independent predictive factor (OR 2.63; 95% CI: 1.02-6.75). Conclusions: A negative mpMRI might be a useful tool to be included in a novel preoperative assessment to patients eligible for HoLEP with a suspicion of PCa in order to avoid an incidental PCa.

In the last two decades deep learning has attracted a lot of attention internationally, solving problems in different application domains and achieving results beyond expectations. For example it has been applied in bioinformatics, game playing, imaging processing, object detection, robotic and drug discovery. One of the main reasons for the incremented use of deep learning algorithms is the need to implement approaches for the analysis of the large amount of data produces in every field, bringing researchers to dedicate their work to deep learning development. One of the main topics discussed up today is the possibility to run the training of deep models in a parallel fashion, so to reduce the time otherwise needed to find the hyperparameters and to make the achievement of the result faster.

Objective: The aim of our study is to describe the use of posterior muscle-fascial reconstruction during urethro-ileal anastomosis in bladder cancer (BC) patients submitted to robot-assisted radical cystectomy (RC) with orthotopic neobladder (ON) and its role in facilitating day- and night-time continence recovery during a 12-month follow up. Materials and methods: We prospectively collected data from 42 consecutive patients who underwent RARC with totally intracorporeal ON and extended pelvic lymph node dissection (PLND) at our Institution from June 2014 to October 2017. Prior to the urethro-neobladder anastomosis we reconstructed the Denonvilliers Fascia (DF) as previously described for radical prostatectomy using a bidirectional barbed suture. Day and night-time recovery rates were reported at 3, 6 and 12 months after surgery, with continent patients being those using either no urinary pads or 1 safety pads. Results: Median age at surgery was 63 yrs, 41 (97.6%) patients were male. 28 (66.7%) patients presented a clinical T2 disease. Median operative time and median ON reconstruction time were 450 minutes and 180 minutes respectively. 13 (31%) individuals had non-organ confined disease, with 11 (26.2%) patients with positive lymph nodes (median 3 positive lymph nodes) and 2 (4.8%) with non-urothelial cancer at final pathologic examination. Median hospital stay and median catheterization time were 7 (IQR 7-8) and 21 (IQR 19-22). During first 30 post-operative days we recorded 7 (16.7%) low-grade Clavien and 2 (4.8%) IIIa Clavien complications, whereas between 30 and 90 postoperative days we recorded 4 (9.5%) low-grade, 4 (9.5) IIIa and 1 (2.4%) IIIb complications. Day-time and night-time continence rates were 61.9% vs 52.4%, 73.8% vs 64.3% and 90.5% vs 73.8% at three, six and twelve months follow up. Day-time continence was significantly superior in the younger group (97% vs 57%, p 0.01); night-time continence rates were also superior among < 70 yrs patients, despite not reaching statistical significance (77% vs 57%, p 0.3). Conclusions: Posterior muscle-fascial reconstruction aids continence recovery in BC patients undergoing RARC with ON, with younger and fitter patients most benefitting from ON reconstruction.

Introduction: Computational chemistry dramatically accelerates the drug discovery process and high-performance computing (HPC) can be used to speed up the most expensive calculations. Supporting a local HPC infrastructure is both costly and time consuming and therefore many research groups are moving from in-house solutions to remote distributed computing platforms. Areas covered: The authors focus on the use of distributed technologies, solutions and infrastructures to gain access to HPC capabilities, software tools and datasets to run the complex simulations required in computational drug discovery. Expert opinion: The use of computational tools can decrease the time to market of new drugs. HPC has a crucial role in handling the complex algorithms and large volumes of data required to achieve specificity and avoid undesirable side-effects. Distributed computing environments have clear advantages over in-house solutions in terms of cost and sustainability. The use of infrastructures relying on virtualization reduces set-up costs. Distributed computing resources can be difficult to access, although web-based solutions are becoming increasingly available. There is a trade-off between cost effectiveness and accessibility in using on-demand computing resources rather than free/academic resources. Graphics processing unit computing, with its outstanding parallel computing power, is becoming increasingly important.

Background: Combination therapy with 5 alpha-reductase inhibitor (5-ARI) and alpha-blocker can be considered as a gold standard intervention for medical management of lower urinary tract symptoms related to benign prostatic hyperplasia (LUTS/BPH). On the other hand, 5-ARI monotherapy and in particular Finasteride alone is currently getting focus of attention especially due to lack of systematic reviews investigating efficacy outcomes and/or adverse events associated. Objectives: Aim of the present critical review was to analyze current knowledge of clinical efficacy and incidence of adverse events associated with 5-ARI treatment for LUTS/BPH. Materials and methods: A systematic review of clinical trials of the literature of the past 20 years was performed using database from PubMed, Cochrane Collaboration and Embase. A total of 8821 patients were included in this study and inclusion criteria for studies selection were: data from randomized clinical trials (RCTs) focusing their attention on the clinical role of Finasteride monotherapy for symptomatic BPH. Parameters of research included prostate specific antigen (PSA), prostate volume (PV), International Prostate Symptom Score (IPPS), postvoid residual urine (PVR), voiding symptoms of IPSS (voiding IPSS), maximum urinary flow rate (Qmax), and adverse events (AEs). Results: Overall 12 original articles were included and critically evaluated. Sample sizes of patient actively treated with finasteride varied from 13 to 1524 cases analyzed in a single study. Follow-up after treatments ranged from 3 to 54 months. The effect of finasteride in reducing prostate volume (PV) was moderate (standardized mean difference (SMD) effect between 0.5 to 0.8 for all trials evaluable) while the effect on IPSS score and Qmax was considered significant (SMD in the 0.2 to 0.5 variation range). No severe AEs and/or psychiatric disorders were retrieved among the studies. Sexual health dysfunctions were significantly influenced by finasteride therapy when compared with placebo treated patients. Conclusions: Although significant clinical benefits of finasteride monotherapy were demonstrated, the effective size of the available reports included in the analysis is limited. Additional head-to-head studies would be needed to re-evaluate clinical efficacy and safety of 5-ARI in combination or not with alpha blockers.

Transitional cell carcinoma (TCC) is the tumor that most frequently affects the urinary tract. The most common location is in the bladder; the diagnosis, as the follow-up, is based on urine cytology, endoscopic, and radiological examinations. Urinary cytology is an important non invasive tool used in the diagnosis and follow-up of patients with TCC. A positive urine cytology result is highly predictive of the presence of TCC, even in the presence of normal cystoscopy, because malignant cells may appear in the urine long time before any cystoscopically visible lesion becomes apparent. The presence of a positive urinary cytology, in the absence of clinical or endoscopic evidence of a TCC, can identify an occult urothelial cancer, located in any site of the urinary tract (upper urinary tract, bladder, prostatic urethra). Most of the urothelial tumors of the renal pelvis and ureters are diagnosed by radiological examinations, but we can observe a high rate of false negatives. In order to improve the diagnostic role of urinary cytology and other conventional examinations, numerous molecular markers have been identified; however, the real clinical application remains unclear. Photodynamic diagnosis and narrow band imaging (NBI) cystoscopy increase the diagnostic accuracy of endoscopic examinations in the presence of lesions not easily detectable. The aim of this review is to analyze the current diagnostic standards in the presence of occult urothelial cancer.

Ultraluminous x-ray sources (ULXs) in nearby galaxies shine brighter than any X-ray source in our Galaxy. ULXs are usually modeled as stellar-mass black holes (BHs) accreting at very high rates or intermediate-mass BHs. We present observations showing that NGC5907 ULX is instead an x-ray accreting neutron star (NS) with a spin period evolving from 1.43~s in 2003 to 1.13~s in 2014. It has an isotropic peak luminosity of about 1000 times the Eddington limit for a NS at 17.1~Mpc. Standard accretion models fail to explain its luminosity, even assuming beamed emission, but a strong multipolar magnetic field can describe its properties. These findings suggest that other extreme ULXs (x-ray luminosity > 10^{41} erg/s) might harbor NSs., 37 pages including Supplementary Material; 7 figures

Background The aim of the work is to describe an original technique of posterior musculofascial reconstruction (PMFR) during robot-assisted radical prostatectomy (RARP). Methods From January 2015 to June 2016, 121 consecutives patients underwent RARP and were submitted to a novel technique of PMFR, using a single 3/0 barbed bidirectional (Filblock®, Assut Europe) suture. The first step of this new technique of PMFR, is to approximate the posterior layer of Denonvilliers fascia (DF) to the posterior part of the sphincteric apparatus. Then, the second step consists in the anastomosis of the posterior blabber neck edge with the posterior urethra edge. We realize the completion of anastomosis clockwise from 7 to 12 o'clock and anticlockwise from 5 to 12 o'clock. Results No leakage of anastomosis was observed and the catheter was removed in the 5th day after surgery. After catheter removal, the urinary recovery of early continence at 3 days was 45% and at 7 days was 75%, while the urinary continence recovery at 1 month was 88% and at 3 months was 94%. Conclusions In our experience this novel approach results feasible in all patient, without extending the operation time and gives a good safety in terms of reduction of bleeding and leakage with shorter urinary continence recovery's time. The aim of the combination of the PMFR and the vesicourethral anastomosis with one bidirectional barbed suture is to have all the advantages of both techniques plus the stability of a single running suture.

Background The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

The e-Science environment developed in the framework of the EU-funded DRIHM project was used to demonstrate its ability to provide relevant, meaningful hydrometeorological forecasts. This was illustrated for the tragic case of 4 November 2011, when Genoa, Italy, was flooded as the result of heavy, convective precipitation that inundated the Bisagno catchment. The Meteorological Model Bridge (MMB), an innovative software component developed within the DRIHM project for the interoperability of meteorological and hydrological models, is a key component of the DRIHM e-Science environment. The MMB allowed three different rainfall-discharge models (DRiFt, RIBS and HBV) to be driven by four mesoscale limited-area atmospheric models (WRF-NMM, WRF-ARW, Meso-NH and AROME) and a downscaling algorithm (RainFARM) in a seamless fashion. In addition to this multi-model configuration, some of the models were run in probabilistic mode, thus giving a comprehensive account of modelling errors and a very large amount of likely hydrometeorological scenarios (> 1500). The multi-model approach proved to be necessary because, whilst various aspects of the event were successfully simulated by different models, none of the models reproduced all of these aspects correctly. It was shown that the resulting set of simulations helped identify key atmospheric processes responsible for the large rainfall accumulations over the Bisagno basin. The DRIHM e-Science environment facilitated an evaluation of the sensitivity to atmospheric and hydrological modelling errors. This showed that both had a significant impact on predicted discharges, the former being larger than the latter. Finally, the usefulness of the set of hydrometeorological simulations was assessed from a flash flood early-warning perspective.

BACKGROUND: To report the perioperative and early functional outcomes of patients undergoing Robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion performed by a single surgeon after a modified modular training. METHODS: The surgeon (A.P.) attained a 30-days modified modular training at a referring Centre mentored by a worldwide-recognized robotic surgeon (P.W.). The training program consisted of: a) e-learning based on 10 hours of theoretical lessons made by the mentor; b) video-session concerning the different steps of the procedure, c) step-by-step in vivo modular training. Demographics, intraoperative data and post-operative complications were recorded for each patient. RESULTS: Twenty-four consecutive patients were prospectively evaluated. Median age was 68.5 years (IQR 59-75). Thirteen (54.2%) and 11 (45.8%) patients received RARC with orthotopic neobladder (ONB) and ileal conduit (IC), respectively. Overall mean (±SD) operative time was 392 (± 34.8) minutes. The median number of lymph node retrieved was 30 (IQR 24-42), the mean intraoperative estimated blood loss (EBL) was 403 mL (± 60) with average hospitalization of 7.8 days (± 2.2). All procedures were completed successfully without open conversion. A statistically significant difference in terms of overall operative time (OT) and urinary diversion operative time (UDOT) was found in favour of IC group compared to ONB group (p=0.002). Overall complication rate was 33%, 7 out of 9 (88%) were graded as minor (Clavien 1-2). Two (22%) major complications (Clavien 3-5) occurred solely on ONB group. CONCLUSIONS: Robot-assisted radical cystectomy with totally intracorporeal urinary diversion is a challenging procedure with a steep learning curve. An adequate modular training with an experienced mentor and a skilled robotic team could be essential to reach these optimal results. Further studies investigating the impact of modular learning curve and a dedicated menthorship on operative and functional outcomes after RARC are needed.

The aim of this study is to analyze the principal advantages of posterior muscolo-fascial reconstruction using knotless barbed sutures (BS) during robot-assisted radical prostatectomy (RARP).We analyzed the available evidence regarding the efficacy and safety of principal BS (Quill™ SRS Angiotech Pharmaceuticals Inc., Vancouver, Canada; V-Loc™ Medtronic, Dublin, Ireland; STRATAFIX™ Ethicon Inc., Somerville, New Jersey; Filbloc® Assut Europe S.p.A., Rome, Italy).We analysed the principal outcomes (operative time and suturing time of urethra-vesical anastomosis, length of catheterization, hospital stay, and postoperative complications rate) reported in literature.In light of our experience, we believe that the utilization of BS during RARP is safe as the development of a new surgical technique of urethrovesical anastomosis offers advantages in terms of continence rate, length of catheterization, and other surgical outcomes. Other studies (prospective trials) are necessary to investigate the real benefits of BS in comparison to conventional sutures (CS).

In this chapter we analyze the development of parallel programs for heterogeneous architectures, that is, workstation composed by multiple CPUs and accelerators, considering different programming models and tools, both commercial and freely available. In particular, we discuss the provided support and achievable performance for each of them with respect to some widely used, computationally intensive algorithms such as the convolution and the N-body algorithms. The aim is to provide a clear measure of the different efficiency figures with respect to the programming paradigm considered, the adopted tool, and the achievable peak performance.

The narrow band imaging (NBI) is a new technology introduced to complement the traditional endoscopy in order to enhance the detection of nonmuscle-invasive bladder cancer and, consequently, to improve the management of the disease. In this review, we considered the most important studies about the use of NBI in the diagnosis and treatment of bladder cancer. Current results demonstrate a greater sensitivity in the diagnosis of bladder cancer and especially a better negative predictive value of cystoscopy enhanced by NBI technology than white light standard cystoscopy. Similarly, improving the performance of endoscopic resection, this new technology would have a positive therapeutic impact in order to decrease residual tumors and relapses. The validation of the results and diffusion of NBI in clinical practice may provide new perspectives in the management of nonmuscle-invasive bladder cancer.

Overactive bladder (OAB) and urinary incontinence, although not life-threatening, are very bothersome chronic health conditions. The limitations of current pharmacological treatment urge the need for novel drugs with alternative mechanisms of action. Huge efforts in this area of research led to the synthesis of several selective and potent β3-adrenoceptor agonists that gained relevance through research during the late 80s and 90s. Mirabegron was the first compound of this new class of drugs that showed preclinical efficacy in several models of storage bladder dysfunction, together with a favorable human pharmacological profile. Having passed the proof-of-concept stage, an extensive clinical development and pharmacology program was performed during the last 10 years, involving10,000 individuals, before mirabegron was granted marketing approval.In this case history, the authors review the milestones in mirabegron's discovery based on a systematic literature review.Thanks to its tolerability and safety/efficacy balance, mirabegron has potential to fill a need for new treatment options for OAB, and paves the way for further development of a completely new class of drugs aimed to treat this condition. However, the exact role of mirabegron in clinical practice has yet to be defined. Further studies are needed in order to clarify, together with post-launch information, critical safety issues and cost-effectiveness in head-to-head comparison with current standard treatments.

The explosion of the data both in the biomedical research and in the healthcare systems demands urgent solutions. In particular, the research in omics sciences is moving from a hypothesis-driven to a data-driven approach. Healthcare is additionally always asking for a tighter integration with biomedical data in order to promote personalized medicine and to provide better treatments. Efficient analysis and interpretation of Big Data opens new avenues to explore molecular biology, new questions to ask about physiological and pathological states, and new ways to answer these open issues. Such analyses lead to better understanding of diseases and development of better and personalized diagnostics and therapeutics. However, such progresses are directly related to the availability of new solutions to deal with this huge amount of information. New paradigms are needed to store and access data, for its annotation and integration and finally for inferring knowledge and making it available to researchers. Bioinformatics can be viewed as the “glue” for all these processes. A clear awareness of present high performance computing (HPC) solutions in bioinformatics, Big Data analysis paradigms for computational biology, and the issues that are still open in the biomedical and healthcare fields represent the starting point to win this challenge.

Objective: To determine efficacy and safety of OnabotulinumtoxinA (BoNT-A) injection therapy in medically refractory patients with lower urinary tract symptoms (LUTS) due to primary bladder-neck dysfunction (PBND). Materials and Methods: Thirty-five consecutive ambulatory males diagnosed with PBND and refractory to medical therapy, with IPSS> 15, Qmax< 15 ml/sec, and total prostate volume

From 1970 to 2012, about 9,000 high-impact weather events were reported globally, causing the loss of 1.94 million lives and damage of $2.4 trillion (U.S. dollars). The scientific community is called to action to improve the predictive ability of such events and communicate forecasts and associated risks both to affected populations and to those making decisions. At the heart of this challenge lies the ability to have easy access to hydrometeorological data and models and to facilitate the necessary collaboration between meteorologists, hydrologists, and computer science experts to achieve accelerated scientific advances. Two European Union (EU)-funded projects, Distributed Research Infrastructure for Hydro-Meteorology (DRIHM) and DRIHM to United States of America (DRIHM2US), sought to help address this challenge by developing a prototype e-science environment providing advanced end-to-end services (models, datasets, and postprocessing tools), with the aim of paving the way to a step change in how scientists can approach studying these events, with a special focus on flood events in complex topographic areas. This paper describes the motivation and philosophy behind this prototype e-science environment together with certain key components, focusing on hydrometeorological aspects that are then illustrated through actionable research for a critical flash flood event that occurred in October 2014 in Liguria, Italy.

Introduction We investigated the diagnostic performance of in-bore endorectal magnetic resonance imaging-guided biopsy (MRI-GB) with a 1.5-T MRI scanner using a 32-channel coil in patients with suspected prostate cancer (PCa). Patients and Methods Seventy patients with ≥ 1 suspicious area found on the preliminary multiparametric MRI scan were enrolled. The index lesion was defined as the lesion with the greatest Prostate Imaging Reporting and Data System, version 2 (PIRADS-v2), score. MRI-GBs were performed with a nonmagnetic biopsy device, needle guide, and titanium double-shoot biopsy gun with dedicated software for needle tracking. Clinically significant PCa was defined as the presence of Gleason score ≥ 7 in the biopsy specimen. Results Seventy index lesions were scheduled for MRI-GB. The median PIRADS-v2 score and the median number of cores per patient was 4 of 5 (interquartile range, 3-5) and 2 (interquartile range, 1-3), respectively. The PCa detection rate was 45.7%. Of the 70 patients, 24 (75%) had clinically significant PCa, with a significant correlation between the PIRADS-v2 score and the Gleason score in the MRI-GB cores ( r = 0.839; 95% confidence interval, 0.535-0.951; P = .003). According to the PIRADs-v2 scheme, the proportion of PCa in the central and anterior regions of the gland was greater in the entire population and in the subgroup of patients with a history of negative transrectal ultrasound-guided biopsy findings ( P ≤ .01 for all). On multivariate analysis, a PIRADS-v2 score of 5 of 5 correlated significantly with the likelihood of PCa at biopsy (hazard ratio, 4.69; 95% confidence interval, 0.92-23.74; P = .04). No major complications were recorded. Conclusion MRI-GB has a high detection rate for PCa, especially for lesions located in the central and anterior regions of the prostate.

Current weather information is one of the facilities supplied to the users by most travel and mobility systems. Most of them relies on one provider, who can deliver a more or less satisfactory coverage on different geographical areas. In this paper, we present the approach and discuss the rationale that drove the design and development of a mashup service for providing meteorological information within the research project TCUBE (“Transport Territory and Tourism“). TCUBE aims at the creation of a platform of services for travel and mobility in urban territory, with initial focus on Genoa metropolitan area. The goal of the project is to study, develop and validate technologies and solutions for the implementation, deployment, and management of advanced information services for citizens and visitors based on enabling technologies and methodologies such as: Open Data; crowd sourcing and social sharing; sensor infrastructures and services based on spatial data. The mashup service presented herein is able to exploit and integrate weather sensor data provided by the free contributions of citizen scientists' Personal Weather Stations belonging to heterogeneous Weather Networks. Design and technical details of our approach are supplied, thus to make it replicable in other similar urban contexts.

The EXTraS project to explore the X-ray Transient and variable Sky searches for coherent signals in the X-ray archival data of XMM-Newton. XMM-Newton performed more than 400 pointed observations in the region of the Large Magellanic Cloud (LMC). We inspected the results of the EXTraS period search to systematically look for new X-ray pulsators in our neighbour galaxy. We analysed the XMM-Newton observations of two sources from the 3XMM catalogue which show significant signals for coherent pulsations. 3XMM J051259.8-682640 was detected as source with hard X-ray spectrum in two XMM-Newton observations, revealing a periodic modulation of the X-ray flux with 956~s. As optical counterpart we identify an early-type star with Halpha emission. The OGLE I-band light curve exhibits a regular pattern with three brightness dips which mark a period of ~1350 d. The X-ray spectrum of 3XMM J051034.6-670353 is dominated by a super-soft blackbody-like emission component (kT ~ 70 eV) which is modulated by nearly 100% with a period of ~1418 s. From GROND observations we suggest a star with r' = 20.9 mag as possible counterpart of the X-ray source. 3XMM J051259.8-682640 is confirmed as a new Be/X-ray binary pulsar in the Large Magellanic Cloud. We discuss the long-term optical period as likely orbital period which would be the longest known from a high-mass X-ray binary. The spectral and temporal properties of the super-soft source 3XMM J051034.6-670353 are very similar to those of RX J0806.3+1527 and RX J1914.4+2456 suggesting that it belongs to the class of double-degenerate polars and is located in our Galaxy rather than in the LMC., Comment: 10 pages, 13 figures, accepted for publication in Astronomy & Astrophysics, new version with minor corrections

Non-muscle-invasive bladder cancer is a common urinary malignancy whose management is a challenge: strong evidence supports the use of passive intravesical chemotherapy in the management of this tumor. Despite current guidelines, the treatment is suboptimal as illustrated by the high risk of recurrence and progression. Bacillus Calmette-Guérin (BCG) is the gold standard for the treatment of high-grade non-muscle-invasive bladder cancer, but in case of disease persistence, after 2 consecutive induction courses of BCG, patients must undergo radical cystectomy. We discuss options for second-line adjuvant therapy for non-muscle-invasive bladder cancer in standard treatment non-responder patients. We investigated the use and application of device-assisted therapy for the intravesical treatment of bladder cancer, such as thermochemotherapy (TCT) and electromotive drug administration (EMDA). Many studies demonstrate their synergistic therapeutic effect, greater than the single treatment with chemotherapy, inducing an increased absorption of the chemotherapeutic agent (Mitomycin C) to the urothelium. TCT and EMDA are safe and effective in terms of outcomes. For the future it will be important to encourage the use of the existing technology within the appropriate clinical indications.

Objective The aim of the present paper is to review findings from the most relevant studies and evaluate the potential of new drugs in treatment of metastatic urothelial cancer. Methods Studies were identified by searching MEDLINE and Pubmed databases up to 2009 using both medical subject heading (Mesh) and a free text strategy with the name of known individual chemotherapeutic drug and the following key words: ‘muscle-invasive bladder cancer’, ‘urothelial/transitional carcinoma’, ‘chemotherapeutics drugs and agents’. At the end of our research in literature we selected 63 articles and we have considered only studies in which almost 30 patients were enrolled. Results Radical cystectomy with pelvic lymph node dissection is the gold standard of treatment for clinically localized muscle-invasive bladder cancer. While more extensive lymph node dissection may have both prognostic and therapeutic significance, effective systemic therapies that eliminate micrometastases may improve outcome. Perioperative chemotherapy can be administered before (neoadjuvant) or after (adjuvant) cystectomy to eradicate subclinical disease and to improve survival. Conclusion The challenge remains as to how to integrate all of the relevant knowledge and data in a systematic manner so that researchers can gain the knowledge needed to devise the best therapeutic and diagnostic strategies. Future improvements in the treatment of advanced bladder cancer will rely not only on the optimization of currently available cytotoxic agents but also on the biologic profile of individual patient tumors and the appropriate therapies that target molecular aberrations unique to this malignancy.

BACKGROUND To analyze data from the cultural examinations of different biological fluids, obtained from urologic patients from January 2007 to April 2010, in order to describe the incidence of infections in our setting. METHODS In the period of reference a urine culture was carried out for every patient admitted, in case of suspected urinary tract infection, a blood culture in case of suspected sepsis, and a wound culture in case of wound infection. RESULTS In the period of investigation 321 patients developed some kind of infection: 589 positive isolations obtained from cultural examinations have been diagnosed in urine (63%), blood (6%), surgical wound (6%), venous central catheter (7%) and other sites (18%) (tip of ureteral and bladder catheters). The most commonly isolated pathogenic agent for all the sites of infection has been Escherichia coli (22.5%). In urine, the most frequently isolated species have been Escherichia coli (27.8%), Enterococcus (12.5%), and Candida spp (9.3%). Escherichia coli (22.9%), Pseudomonas (5.7%), and Staphylococcus aureus (3.5%) were the most frequently found pathogenic agents responsible for sepsis, compared to others. In the period of investigation we have recorded 35 episodes of sepsis. CONCLUSIONS Empiric antibiotic therapy is frequent in cases of clinical evidence of infection, before the identification of the causative microorganism is available; therefore, it is important to know which are the bacterial species mainly responsible for these specific infections. We need continuous surveillance of infections and the improvement in the use of antibiotic therapy in order to limit the antimicrobial resistance.

High-intensity focused ultrasound (HIFU) is a minimally invasive therapy applied for prostate cancer that capitalizes on the coagulation necrosis that occurs at temperatures greater than 60°C. Owing to a lack of long-term follow-up data the procedure is still considered experimental treatment. As primary therapy, HIFU is indicated in patients aged ≥70 years with clinical organ-confined disease, although it has also been used, with encouraging results, as first line salvage therapy after definitive treatment, and in locally advanced (T3-4) and non-metastatic hormone-resistant prostate cancer. Morbidity associated with this treatment method appears to be low and includes urinary retention (1-9%), urethral stricture (4-14%), incontinence (1-15%), erectile dysfunction (13-53%) and rectourethral fistulae (0-3%). The risk of complications increases with repeated treatments. A few studies have recently been published on HIFU as focal therapy. HIFU technology can be enhanced using means such as ultrasound microbubble contrast agents for assessment of therapy efficacy, magnetic resonance imaging to guide the enhancement of heat rate, and localized drug and gene delivery.

Aim: We report the oncological and functional outcomes of a population of elderly patients who underwent robotic-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (IUD) at a single high-volume center with extensive experience in robotic surgery.Patients and Methods: Each procedure was performed by a single main surgeon, who previously attained a 30-day modified modular training program at a referring center. None technical variation was performed, and the surgical technique was performed exactly as taught. Demographics, intraoperative data, and postoperative complications were recorded for each patient of the aforementioned population. Results: From July 2015 to December 2018, we submitted to RARC with totally IUD at our institution 29 elderly patients (aged ≥75 years). Median age was 78 years (interquartile range [IQR]: 76–82). Eleven (37.9%), 12 (41.4%), and 6 (20.7%) patients received RARC with ureterocutaneostomy, ileal conduit, and orthotopic neobladder, respectively. Overall, median operative time was 360 min (IQR: 270–410). The median number of lymph node retrieved was 24 (17–34), the median intraoperative estimated blood loss (EBL) was 200 mL (150–300), with median hospitalization time of 7 days (IQR: 6–9). Each procedure was successfully completed without open conversion. A statistically significant reduction was found in the operative time, when compared to a population of younger patients (aged

Hem-o-Lok clips (Weck Surgical Instruments, Teleflex Medical, Durham, North Carolina, USA) are widely used in robot-assisted laparoscopic radical prostatectomy because of their easy application and secure clamping. To date, there have been some reports of their migration into the urinary tract, causing urethral erosion, bladder neck contractures orcalculus formation. We report a case of endourethral migration of a hem-o-lok after robot-assisted laparoscopic prostatectomy. The hem-o-lok was almost completely endoluminal and attached to one end at the vesico-urethral anastomosis. The hem-o-lok was easily removed cystoscopically by using an endoscopic forceps.

Overactive bladder (OAB) is a highly prevalent urinary syndrome with a profound impact on quality of life (QoL) of affected patients and their family because of its adverse effects on social, sexual, interpersonal, and professional function. Cost-of-illness analyses showed the huge economic burden related to OAB for patients, public healthcare systems, and society, secondary to both direct and indirect costs; however, intangible costs related to QoL impact are usually omitted from these analyses. Recently many novel treatment modalities have been introduced and the need to apply the modern methodology of health technology assessment to these treatment strategies was immediately clear in order to evaluate objectively their value in term of both improvement in length/quality of life and costs. Health utilities are instruments that allow a measurement of QoL and its integration in the economic evaluation using the quality-adjusted life-years model and cost-utility analysis. The development of suitable instruments for quantifying utility in the specific group of OAB patients is vitally important to extend the application of cost-utility analysis in OAB and to guide healthcare resources allocation for this disorder. Studies are required to define the cost-effectiveness of available pharmacological and nonpharmacological therapy options for this disorder.

Bladder cancer is among the top eight most frequent cancers. Its natural history is related to a combination of factors that impact on its aggressiveness. Cystoscopy and urine cytology are the currently used techniques for the diagnosis and surveillance of non-invasive bladder tumors. The sensitivity of urine cytology for diagnosis is not high, particularly in low-grade tumors. The combination of voided urine cytology and new diagnostic urine tests would be ideal for the diagnosis and follow-up of bladder cancer. However, in order to have some clinical utility, new diagnostic and/or prognostic markers should achieve better predictive capacity that the currently used diagnostic tools. None of the markers evaluated over the last years showed remarkable sensitivity or specificity for the identification of any of the diverse types of bladder cancer in clinical practice. The limitations of the known prognostic markers have led to the research of new molecular markers for early detection of bladder cancer. This research focused in particular on the discovery of biomarkers capable of reducing the need for periodic cystoscopies or, ideally, offering a non-invasive examination instead. In this review, we will examine various new markers of bladder cancer and their value in the diagnosis and follow-up of non-muscle-invasive bladder cancer. When compared with urine cytology, which showed the highest specificity, most of these markers demonstrated an increased sensitivity.

Background: To evaluate the difference at different steps of follow-up of the postoperative quality of life (QoL) in patients who had undergone radical cystectomy and ileal orthotopic neobladder derivation. Patients and Methods: A multicentric, cross-qualitative study was performed in 5 Italian centers of reference for the treatment of bladder cancer. One hundred seventy one patients who underwent radical cystectomy and creation of ileal orthotopic neobladder according to ‘Vescica Ileale Padovana' between 2006 and 2011 have been analyzed. The validated and dedicated questionnaires EORTC QLQ-C30, IOB-PRO and EORTC QLQ-BLM30 were used. Results: All data gathered were then processed, specifically means ± SD were included for comparison during 4 periods of follow-up (quartile): the first ranging from 1 to 18 months; the second ranging from 19 to 36 months; the third from 37 to 72 months and the fourth >72 months. Cancer-specific and health-related factors were analyzed separately, and the change was determined during follow-up. Conclusions: The global QoL, highlighted by validated cancer-specific and health-related questionnaires, is certainly on a satisfactory level. Thus, the education of the patient, the exploration of the pros and cons of an orthotopic neobladder and the active participation in treatment decision seem to be the keys to better improve the post-operative QoL during the follow-up period.

Bladder cancer treatment is a challenge for both urologists and oncologists. Particularly during these last years many changes have been made in the management of superficial bladder cancer. In the case of superficial bladder cancer, intravesical instillation of chemo/immunotherapeutic agents after transurethral resection is the standard. The treatment goals include: complete removal of the initial tumor, prevention of recurrences and inhibition of disease progression. This work aims at reviewing the new developments in the therapeutic field of superficial bladder cancer. A growing trend involves the use of multimodality treatment to obtain the activation of the host immunity against the tumor, and to enhance the cytotoxic effects of chemotherapeutic agents. The new therapeutic modalities, which are under preclinical and clinical investigations, are showing promising results.

Bladder cancer treatment is a challenge for both urologists and oncologists. Particularly during these last years many changes have been made in the management of superficial bladder cancer. In the case of superficial bladder cancer, intravesical instillation of chemo/immunotherapeutic agents after transurethral resection is the standard. The treatment goals include: complete removal of the initial tumor, prevention of recurrences and inhibition of disease progression. This work aims at reviewing the new developments in the therapeutic field of superficial bladder cancer. A growing trend involves the use of multimodality treatment to obtain the activation of the host immunity against the tumor, and to enhance the cytotoxic effects of chemotherapeutic agents. The new therapeutic modalities, which are under preclinical and clinical investigations, are showing promising results.

During a search for coherent signals in the X-ray archival data of XMM-Newton, we discovered a modulation at 1.2 s in 3XMM J004301.4+413017 (3X J0043), a source lying in the direction of an external arm of M 31. This short period indicates a neutron star (NS). Between 2000 and 2013, the position of 3X J0043 was imaged by public XMM-Newton observations 35 times. The analysis of these data allowed us to detect an orbital modulation at 1.27 d and study the long-term properties of the source. The emission of the pulsar was rather hard (most spectra are described by a power law with $\Gamma < 1$) and, assuming the distance to M 31, the 0.3-10 keV luminosity was variable, from $\sim$$3\times10^{37}$ to $2\times10^{38}$ erg s$^{-1}$. The analysis of optical data shows that, while 3X J0043 is likely associated to a globular cluster in M 31, a counterpart with $V\gtrsim22$ outside the cluster cannot be excluded. Considering our findings, there are two main viable scenarios for 3X J0043: a peculiar low-mass X-ray binary, similar to 4U 1822-37 or 4U 1626-67, or an intermediate-mass X-ray binary resembling Her X-1. Regardless of the exact nature of the system, 3X J0043 is the first accreting NS in M 31 in which the spin period has been detected., Comment: To appear in MNRAS Letters; 2 color figures, 2 tables; 5 pages plus full Table 1 (1 page)

X-ray emission from Young Stellar Objects (YSOs) is crucial to understand star formation. A very limited amount of X-ray results is available for the protostellar (ClassI) phase. A systematic search of transient X-ray phenomena combined with a careful evaluation of the evolutionary stage offer a widely unexplored window to our understanding of YSOs X-ray properties. Within the EXTraS project, a search for transients and variability in the whole XMM-Newton archive, we discover transient X-ray emission consistent with ISO-Oph 85, a strongly embedded YSO in the rho Ophiuchi region, not detected in previous time-averaged X-ray studies. We extract an X-ray light curve for the flare and determine its spectral parameters from XMM-Newton/EPIC (European Photon Imaging Camera) data using quantile analysis. The X-ray flare ($2500\,s$), the only one detected in the XMM-Newton archive for ISO-Oph 85, has a luminosity of $LogL_X[erg/s]=31.1$ and a spectrum consistent with a highly-absorbed one-component thermal model ($N_H=1.0^{+1.2}_{-0.5}10^{23}\,cm^{-2}$, $kT=1.15^{+2.35}_{-0.65}\,keV)$. We set an upper limit of $LogL_X[erg/s], 10 pages, 7 figures, 2 tables Accepted for publication by Astronomy&Astrophysics

The EXTraS project (Exploring the X-ray Transient and variable Sky) will characterise the temporal behaviour of the largest ever sample of objects in the soft X-ray range (0.1-12 keV) with a complex, systematic and consistent analysis of all data collected by the European Photon Imaging Camera (EPIC) instrument onboard the ESA XMM-Newton X-ray observatory since its launch. We will search for, and characterize variability (both periodic and aperiodic) in hundreds of thousands of sources spanning more than nine orders of magnitude in time scale and six orders of magnitude in flux. We will also search for fast transients, missed by standard image analysis. Our analysis will be completed by multiwavelength characterization of new discoveries and phenomenological classification of variable sources. All results and products will be made available to the community in a public archive, serving as a reference for a broad range of astrophysical investigations., 4 pages, 1 figure. Refereed Proceeding of "The Universe of Digital Sky Surveys" conference held at the INAF - Observatory of Capodimonte, Naples, on 25th-28th November 2014, to be published in the Astrophysics and Space Science Proceedings, edited by Longo, Napolitano, Marconi, Paolillo, Iodice

The EXTraS project (Exploring the X-ray Transient and variable Sky) will harvest the hitherto unexplored temporal domain information buried in the serendipitous data collected by the European Photon Imaging Camera (EPIC) instrument onboard the ESA XMM-Newton X-ray observatory since its launch. This will include a search for fast transients, as well as a search and characterization of variability (both periodic and aperiodic) in hundreds of thousands of sources spanning more than nine orders of magnitude in time scale and six orders of magnitude in flux. X-ray results will be complemented by multiwavelength characterization of new discoveries. Phenomenological classification of variable sources will also be performed. All our results will be made available to the community. A didactic program in selected High Schools in Italy, Germany and the UK will also be implemented. The EXTraS project (2014-2016), funded within the EU/FP7 framework, is carried out by a collaboration including INAF (Italy), IUSS (Italy), CNR/IMATI (Italy), University of Leicester (UK), MPE (Germany) and ECAP (Germany)., 6 pages, 1 figure. Proceedings of "Swift: 10 years of Discovery", to appear in PoS

A proper representation of protein surfaces is an important task in bioinformatics and biophysics. In a previous work we described a parallel workflow, based on the isosurface extraction and the CUDA architecture, able to produce high-resolution molecular surfaces based on the Van der Waals, Solvent Accessible, Richards-Connolly and Blobby definitions. In particular it is able to create surfaces composed by hundred millions triangles in less than 30 s using a Nvidia GTX 580, with speedup values up to 88. However in most application such number of triangles can be difficult to manage. In this paper we present an extension able to reduce the size of the surfaces by performing a simplification step, keeping however an high quality of the results. In particular the focus of the paper is on the efficient use of heterogeneous compute capabilities available on present workstations: the large surface produced using the CUDA device is progressively transferred and simplified on the host using the multicore CPU.