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Male stress urinary incontinence, which has radical prostatectomy as the main aetiology, affects about 39% of the adult male population and is one of the complications of radical prostatectomy with the greatest impact on the quality of life of patients. There are a wide range of treatments for stress urinary incontinence available to the urologist, ranging from conservative treatments to surgical treatments, from minimally invasive procedures to the implant of artificial sphincter prosthesis. The aim of this work is to define the state-of-the-art of surgical treatments for male stress urinary incontinence, analyzing the most recent studies in the literature and evaluating the available scientific evidence.

Omics sciences are able to produce, with the modern high-throughput techniques of analytical chemistry and molecular biology, a huge amount of data. Next generation sequencing (NGS) analysis of diseased somatic cells, genome wide identification of regulatory elements and biomarkers, systems biology studies of biochemical pathways and gene network, and novel bioactive compounds discovery and design are examples of the great advantages that high-performance computing (HPC) can provide to omics sciences, providing a fast translation of biomolecular results to the clinical practice. Massive parallel clusters, distributed technologies such as grid and cloud computing, and on-chip supercomputing such as GPGPU and Xeon Phi devices represent well-established solutions in research laboratories, but their capabilities should be widespread by clinical and healthcare experts to reach their full potential. Additionally to compute-intensive applications, health care problems are concerned with data-intensive applications. Managing terabytes of data requires specific technologies such as redundant facilities, shared and distributed file systems, clustered databases, indexing and searching processes, and dedicated network configuration. The aim of this special issue is to present the latest advances in the field of omics data processing with high-performance computing solutions and big data analysis paradigms, showing the potential repercussions of these technologies in translational medicine. In particular, a review paper, authored by the editors, “Managing, analysing and integrating big data in medical bioinformatics: open problems and future perspectives,” is a survey about open problems and future perspectives in the management, analysis, and integration of big data in medical bioinformatics, while the eleven selected research papers present novel concepts and important results about the application of HPC techniques in the field of computational and systems biology. Regarding the research papers, three contributions propose novel or improved implementation of parallel algorithms. C. Misale et al. in their paper entitled “Sequence alignment tools: one parallel pattern to rule them all?” are engaged in NGS and investigated the performance of the widely used alignment tools Bowtie2, BWA, and BLASR. They advocate high-level parallel programming as an alternative design strategy for next generation alignment tools. The master-worker FastFlow pattern to Bowtie2 and BWA-MEM increases the speedup for both applications and is compared to manually tuned implementations. The paper by M. W. Al-Neama et al. “An Improved distance matrix computation algorithm for multicore clusters” is concerned with an efficient implementation of distance matrix computation on multicore clusters that finds wide application in multiple sequence alignment. The implementation is mainly based on MPI and OpenMP libraries and achieves improved speedups with respect to the public parallel implementation of ClustalW-MPI. M. Aldinucci et al. in the paper entitled “On designing multicore-aware simulators for systems biology endowed with online statistics” describe a multicore aware simulation algorithm that can be applied in the field of systems biology for online statistics and data mining. The main methodology is based on the acceleration of the simulation of stochastic models and the analysis of the obtained results, where the application case relies on a general framework for the modelling of biological systems and their stochastic behaviour called calculus of wrapped compartments. The paper by P. Cazzaniga et al. “Massive exploration of perturbed conditions of the blood coagulation cascade through GPU parallelization” belongs to the class of research on on-chip acceleration of the behaviour of biological systems in different conditions. The paper is concerned with GPU implementation of a deterministic systems biology simulator, which is applied for the exploration of perturbed conditions of the blood coagulation cascade using GPU hardware. It is based on the automatic derivation of the system of ordinary differential equations that represent the blood system in parallel. Most interesting results are obtained by one-dimensional and two-dimensional sweep of simulation parameters and achieved speedup is around 181x. Three papers discuss approaches based on the combined use of the parallel/distributed computing with the usage of GPU-based devices. The paper by G. D. Guerrero et al. “A performance/cost evaluation for a GPU-based drug discovery application on volunteer computing” discusses the benefits of volunteer computing to scale bioinformatics applications as an alternative to own large GPU-based local infrastructures. They used as benchmark a GPU-based drug discovery application called BINDSURF and the Ibercivis, which relies on BIOINC, as the reference platform. D. D'Agostino et al. in the paper entitled “Parallel solutions for voxel-based simulations of reaction-diffusion systems” present a comparison between MPI and a GPU implementation of a stochastic simulator able to consider both time and space in its simulations. This algorithm is also crowd-aware and it has been tested on a gene regulatory network, whose behaviour is influenced by both the small number of molecules involved and the conformation of the DNA in the nucleus. The paper by J. Colmenares et al. entitled “A combined MPI-CUDA parallel solution of linear and nonlinear Poisson-Boltzmann equation” is on a combined MPI/CUDA approach for the solution of linear and nonlinear Poisson-Boltzmann equation, which is very relevant to modeling the electrostatic potential generated by a system of charged particles immersed in an ionic solution. Their work is mainly based on the implementation of a full Poisson-Boltzmann solver based on a finite-difference scheme on a heterogeneous parallel system comprised of a cluster of multicores and multi-GPUs. Overall speedups of around 20x are achieved. Two papers investigate computational biology problems that present scalability issues in their real-life application. The paper by M. Lauria “Rank-based miRNA signatures for early cancer detection” describes a new signature definition and analysis method to be used as biomarker for early cancer detection. This approach is based on the construction of a reference map of transcriptional signatures of both healthy and cancer affected individuals using circulating miRNA from a large number of subjects. T. Garcia-Valverde et al. in the paper entitled “Heart health risk assessment system: a nonintrusive proposal using ontologies and expert rules” suggest ontology and expert rules for creating a heart health risk assessment system. Available knowledge about persons gained by sensors embedded in smartphones and smartwatches allows for different levels of alerts or suggestions for the users when the intensity of the activity is detected as dangerous for their health. Finally, two papers discuss distributed approaches to large-scale computation. J. Kruger et al. in the paper entitled “Performance studies on distributed virtual screening” elaborate the performance for virtual high-throughput screening in regard to distributed computing on the example of UNICORE. They considered not only the runtime of the docking itself, but also the effort required for structure preparation. Performance studies were conducted via the workflow-enabled science gateway MoSGrid (Molecular Simulation Grid). A. Ragothaman et al. in the paper entitled “Developing eThread pipeline using SAGA-pilot abstraction for large-scale structural bioinformatics” present a cloud infrastructure for running eThread, a metathreading protein structure modelling tool for structural bioinformatics, using Amazon EC2. Authors supplied interesting insights of how continuing advances in genome sequencing technologies result in rapidly decreasing costs of experiments making them affordable for small research groups. Moreover, they present how it is possible to exploit modern cloud infrastructures to execute large-scale calculations by coordinating possibly heterogeneous virtual machine instances. Ivan Merelli Horacio Perez-Sanchez Sandra Gesing Daniele D'Agostino

Besides core project partners, the SCI-BUS project also supported several external user communities in developing and setting up customized science gateways. The focus was on large communities typically represented by other European research projects. However, smaller local efforts with the potential of generalizing the solution to wider communities were also supported. This chapter gives an overview of support activities related to user communities external to the SCI-BUS project. A generic overview of such activities is provided, followed by the detailed description of three gateways developed in collaboration with European projects: the agINFRA Science Gateway for Workflows for agricultural research, the VERCE Science Gateway for seismology, and the DRIHM Science Gateway for weather research and forecasting.

There is an increasing awareness of the pivotal role of noise in biochemical processes and of the effect of molecular crowding on the dynamics of biochemical systems. This necessity has given rise to a strong need for suitable and sophisticated algorithms for the simulation of biological phenomena taking into account both spatial effects and noise. However, the high computational effort characterizing simulation approaches, coupled with the necessity to simulate the models several times to achieve statistically relevant information on the model behaviours, makes such kind of algorithms very time-consuming for studying real systems. So far, different parallelization approaches have been deployed to reduce the computational time required to simulate the temporal dynamics of biochemical systems using stochastic algorithms. In this work we discuss these aspects for the spatial TAU-leaping in crowded compartments (STAUCC) simulator, a voxel-based method for the stochastic simulation of reaction-diffusion processes which relies on the Sτ-DPP algorithm. In particular we present how the characteristics of the algorithm can be exploited for an effective parallelization on the present heterogeneous HPC architectures.

The increasing awareness of the pivotal role of noise in biochemical systems has given rise to a strong need for suitable stochastic algorithms for the description and the simulation of biological phenomena. However, the high computational demand that characterizes stochastic simulation approaches coupled with the necessity to simulate the models several times to achieve statistically relevant information on the model behaviors makes the application of such kind of algorithms often unfeasible. So far, different parallelization approaches have been employed to reduce the computational time required for the analysis of biochemical systems modeled using stochastic algorithms. Most of the proposed solutions use an embarrassingly parallel approach to run in parallel several simulations using the cores of a workstation and/or the nodes of a cluster. In this work we present the Spatial TAU-leaping in Crowded Compartments (STAUCC) simulator, a software that relies on an efficient CUDA implementation of the Stau-DPP algorithm, a voxel-based method for the stochastic simulation of Reaction-Diffusion processes. We evaluate its application and performance for the modeling of diffusion processes simultaneously occurring within a space represented considering different levels of granularity. © 2014 IEEE.

Bladder cancer represents the second most common neoplasm of the urinary tract and the fourth in general among all the neoplastic pathologies for the male gender; in females, it is the eighth most frequent among all cancers. At the initial diagnosis, 70% of bladder tumors are non-muscle invasive. Treatment of this stage is multimodal, both surgical and pharmacological; the aim is not only to remove the tumor completely but also to prevent tumor recurrence and to inhibit its progression. The treatment for non-muscle invasive bladder cancer is a current topic in the scientific community and it is represented by the endoscopic resection of the tumor, which is generally followed by the adjuvant intravesical treatment with chemotherapy or immunotherapy agents, according to the different risk groups. Benefits and limits of intravesical therapies have been known for long; the aim of this study is to present new drugs or new treatment patterns which could emerge as a valid therapeutic alternative to conventional treatments, given the fact that, regardless of the type of treatment, 2/3 of the patients with a diagnosis of non-muscle invasive bladder cancer have a disease recurrence, and the 10–20% of these show a progression to a muscle-invasive tumor. Furthermore, the failure of intravesical therapy implies another therapeutic option, such as radical cystectomy for non-muscle invasive bladder cancer. According to this fact, new strategies include the activation of host immune system and the optimization of cytotoxic effects of chemotherapeutic drugs. Although most of these studies are still in a pre-clinical phase, the experimental outcomes and the initial results in humans are encouraging.

Cloud computing opens new perspectives for small-medium biotechnology laboratories that need to perform bioinformatics analysis in a flexible and effective way. This seems particularly true for hybrid clouds that couple the scalability offered by general-purpose public clouds with the greater control and ad hoc customizations supplied by the private ones. A hybrid cloud broker, acting as an intermediary between users and public providers, can support customers in the selection of the most suitable offers, optionally adding the provisioning of dedicated services with higher levels of quality. This paper analyses some economic and practical aspects of exploiting cloud computing in a real research scenario for thein silicodrug discovery in terms of requirements, costs, and computational load based on the number of expected users. In particular, our work is aimed at supporting both the researchers and the cloud broker delivering an IaaS cloud infrastructure for biotechnology laboratories exposing different levels of nonfunctional requirements.

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).Thirty-five consecutive ambulatory males diagnosed with PBND and refractory to medical therapy, with IPSS 15, Qmax 15 ml/sec, and total prostate volume 30 cm(3), were screened from January 2010 to December 2011. Eligible patients underwent transurethral bladder-neck injection of BoNT-A (200 U, 50 U/ml × 4 sites) and were assessed at baseline, 2-, 6-, 9-, and 12-month postprocedure and until duration of clinical response. The primary outcome was the change from baseline in total IPSS, and secondary outcome were storage- and voiding-IPSS, QoL score, Qmax, and postvoiding residual volume (PVR), patient-reported outcomes. Adverse effects were also recorded, including ejaculatory dysfunctions.Of 30 enrolled patients (mean age 33.8 years), 29 (96.7%) completed the study. A statistically significant improvement of total IPSS was observed from 21.9 at baseline, to 7.8, 10.3, and 16.6 at 2, 6, and 9 months, respectively (P 0.000). Statistically significant improvements from baseline of storage- and voiding-IPSS, QoL score, Qmax, and PVR were also observed until 9-month postprocedure. The proportion of patients with overall satisfaction was favorable although decreasing from 80% at 2 months, to 44.8% at 12 months. No significant adverse effects or ejaculatory dysfunctions were noted.BoNT-A injection therapy appears effective and safe in medically refractory men with PBND, although repeated procedures are required for long-term sustained benefit. Randomized controlled trials are warranted in order to corroborate these results.

Objective: It was the aim of this study to evaluate the accuracy of the measurement of tumor size comparing the objective size with that measured by preoperative cystoscopy, by preoperative ultrasound (US) and with the diameter described by the operator before the transurethral resection. Patients and Methods: This study included 100 patients with bladder papillary endoscopic features of single or multiple neoplasms who were candidates for transurethral resection. The sizes of the same neoplasms measured during preoperative cystoscopy, preoperative US and described by the operator before the transurethral resection were evaluated. A statistical analysis of the errors of measurement was performed if compared with an objective measurement done with an ureteral catheter. Results: The statistical analysis of the data shows that there are no substantial differences between the objective and subjective measurement, and therefore, the measurements reported by individual operators are reliable. On the contrary, the diameters given by preoperative cystoscopy and US differ significantly from the objective measurement. Conclusions: This study shows that the most reliable measurement is the subjective measurement made directly by the urologist in the operating room.

The aim of the present paper was to review findings from the most relevant studies and to evaluate the value of current chemotherapy and surgery in advanced unresectable and metastatic bladder cancer. Studies were identified by searching the MEDLINE® and PubMed® databases up to 2011 using both medical subject heading (Mesh) and a free text strategy with the name of the known individual chemotherapeutic drug and the following key words: ‘muscle-invasive bladder cancer’, ‘chemotherapeutics agents’, and ‘surgery in advanced bladder cancer’. At the end of our literature research we selected 141 articles complying with the aim of the review. The results showed that it has been many years since the MVAC (methotrexate, vinblastine, adriamycin, cisplatin) regimen was first developed. The use of cisplatin-based combination chemotherapy is associated with significant toxicity and produces long-term survival in only approximately 15–20% of patients. Gemcitabine + cisplatin represents the gold standard in the treatment of metastatic bladder cancer. In conclusion, the optimal approach in the management of advanced urothelial cancer continues to evolve. Further progress relies on the expansion of research into tumor biology and an understanding of the underlying molecular ‘fingerprints’ that can be used to enhance diagnostic and therapeutic strategies. Cisplatin-based therapy has had the best track record thus far.

Study Type - Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Peri-operative pelvic floor muscle training reduces urinary incontinence for men undergoing radical prostatectomy (RP). A preoperative biofeedback session, combined with postoperative pelvic floor muscle training, and assisted sessions on a monthly basis only, is an effective low-intensity programme to improve recovery of continence in patients undergoing RP.To evaluate the efficacy of preoperative biofeedback (BFB) combined with an assisted low-intensity programme of postoperative perineal physiokinesitherapy in reducing the incidence, duration and severity of urinary incontinence (UI) in patients undergoing radical prostatectomy (RP).A prospective, single-centre, randomized controlled clinical study was designed. • The intervention group received a training session with BFB, supervised oral and written instructions on Kegel exercises and a structured programme of postoperative exercises on the day before open RP. After RP, patients received control visits, including a session of BFB, at monthly intervals only. • The control group received, after catheter removal, only oral and written instructions on Kegel exercises to be performed at home. Patients received control visits at 1, 3 and 6 months after catheter removal. • At each visit the number of incontinence episodes, the number of pads used and patient-reported outcome measures (International Consultation on Incontinence Questionnaire on Urinary Incontinence [ICIQ-UI], [ICIQ]-Overactive Bladder [OAB], University of California, Los Angeles-Prostate Cancer Index [UCLA-PCI], International Prostate Symptom Score-Quality of Life [IPSS-QoL]) were assessed in both groups. All patients were followed-up for a period of at least 6 months after catheter removal. • The primary outcome was the recovery of continence, strictly defined as a ICIQ-UI score of zero.Overall, 34 consecutive patients were eligible and 32 were available for the final analysis: 16 patients for each study group. The two groups were homogeneous for all pre- and intraoperative features examined. • In the intervention group, continence had been achieved by six, eight and 10 patients at 1-, 3- and 6-month follow-ups, respectively, vs no patients (P= 0.02), one patient (P= 0.01) and one patient (P= 0.002) in the control group at each follow-up, respectively. • The analysis of the UCLA-PCI and ICIQ-OAB scores, the number of incontinence episodes per week and the number of pads per week showed significant differences in favour of patients in the intervention group at 3 and 6 months. • Patients in the intervention group reported better IPSS-QoL scores at all follow-up times but the difference did not reach statistical significance.Preoperative BFB combined with a postoperative programme of perineal physiokinesitherapy and assisted sessions on a monthly basis only, is a treatment strategy significantly more effective than the standard care in improving recovery of continence in patients undergoing RP. • The impact on QoL appeared less evident, although a trend for a better QoL was observed in the intervention group.

The allocation of jobs to a set of heterogeneous resources, as in common e-Science environments, is a key issue for their efficient use. To reach a better coupling and improve execution times of applications, a consolidated though challenging opportunity is the benchmarking of resources. In this direction, we propose to exploit two complementary approaches, the micro and application-driven benchmarks, which allow to grasp the behavior of computational contexts with respect to more realistic workloads and to lead to a more efficient assignment of the submitted jobs to resources. To evaluate the appropriateness of our methodology an experimentation on a test bed was carried-out. A first comparison of benchmarking results highlighted differences in performance amongst the two levels of benchmarks. Moreover the appropriateness of adopting benchmarking information to rank resources was also confirmed by examining different allocation strategies through a queuing network simulator.

Purpose Patients with non-muscle invasive bladder cancer recurrence after 2 induction courses of BCG are eligible for radical cystectomy. So, in the last years research to discover new drugs for the management of non-muscle invasive bladder cancer recurrence after failure of first and second line therapy is ongoing. In accordance to the results obtained with BCG, whose mechanism depends on the induction of the T helper 1 (TH1) immune response, we investigated the activity of a Toll-like receptor (TLR) 2 ligand, named Helicobacter Pylori Neutrophil Activating Protein (HP-NAP), that we recently demonstrated being able of enhancing the differentiation of Th1 cells, both in vitro and in vivo, because of its ability to create an IL-12 enriched milieu. Materials and Methods We show here, in a mouse model of bladder neoplasm implants, that local administration of HP-NAP decreases tumor growth by inducing tumor necrosis. Results The result is joined up with a massive cluster of both CD4+ and CD8+ IFN-γ+ cells, within neoplasm and regional lymph nodes. It is of note that HP-NAP-treated tumors show also a reduced vascularization due to the anti-angiogenic activity of IFN-γ induced by HP-NAP. Conclusions The present study suggests that the activity of HP-NAP against urothelial tumor burden warrants subsequent in vivo studies.

Background Robotic technology is used in multiple fields of surgery, especially radical prostatectomy in patients with prostate cancer. The purpose of this study was to evaluate the introduction of robotic technology in the Italian Public Heath-care context, from the perspective of the Health Technology Assessment (HTA). An economic analysis that compares the costs and effectiveness of the method was developed. Data were compared with those of the most important international literature, analyzing structural and organizational problems related to the method. Materials and Methods A systematic review of literature on tertiary literature (Health Technology Assessment reports) and secondary (systematic reviews) published since 2002 was conducted. The review was also conducted on more recent primary literature regarding the clinical effectiveness and the economic analysis in the fields of surgery where da Vinci® robot is most promising. Results 18 studies were selected out of a total of 65 evaluated. The “Break-Even Point” (BEP) is the minimum number of cases needed to be treated in order to achieve a balance between costs and revenues, below which the system is losing money. It was calculated that the total fixed costs are € 378,000 and variable costs are € 3,810 per surgery. Considering that the current value of DRG (Diagnosis-Related Group) refunded by the public Health-care system is actually € 4,553, the BEP would be achieved performing 508 surgeries, so that the robotic technology does not generate neither profit nor loss. Conclusions It is not possible to demonstrate the superiority of robotic surgery in terms of efficacy. The robotic surgery is safe and effective only if performed by surgical teams with relevant experience. Considering the reported case of an Italian University Hospital with public Health-care system refund, the BEP target of 508 radical prostatectomies could be achieved after a few years. The use of the robot in multiple fields on one hand shortens recovery time costs, but on the other hand increases costs due to organizational issues. The value of the DRG refund does not appear adequate to new robotic technology.

Objectives: Non-muscle-invasive bladder cancer is characterized by a high recurrence rate after primary transurethral resection. In case of bacillus Calmette-Guérin-refractory neoplasms, cystectomy is the gold standard. In this study the effects of thermochemotherapy with mitomycin C were evaluated in high-risk bladder cancer nonresponders to previous therapy. Patients and Methods: Between January 2006 and December 2009, 30 patients were enrolled with recurrent stage carcinoma in situ, Ta and T1, grade G1 to G3 non-muscle-invasive bladder cancer refractory to chemotherapy or immunotherapy and so becoming suitable for radical cystectomy. All patients underwent endovesical thermochemotherapy: 16 patients underwent a prophylactic scheme and 14 patients underwent an ablative scheme. Results: All the patients completed the study. The mean follow-up for all the patients enrolled was 14 months. Thirteen of 30 patients (43.30%) were disease free and 17 patients (56.70%) had recurrence. In the prophylactic group, 7 of 16 patients (43.75%) were disease free and 9 patients (46.25%) had tumor recurrence; no progression was observed. In the ablative group, 3 patients (17, 64%) had progression to muscle-invasive disease. Side effects were generally mild. Conclusions: Thermochemotherapy could be considered an additional tool in patients refractory to intravesical therapies before considering early cystectomy.

Purpose: Carcinoma in situ represents high grade anaplasia of the bladder mucosa. Intravesical immunotherapy with bacillus Calmette-Guerin is the gold standard treatment for patients with carcinoma in situ. Patients with carcinoma in situ refractory to bacillus Calmette-Guerin are candidates for major surgery such as radical cystectomy. We identified the maximum tolerated dose and the recommended dose, and evaluated the safety profile of paclitaxel-hyaluronic acid bioconjugate given by intravesical instillation to patients with carcinoma in situ refractory to bacillus Calmette-Guerin. Materials and Methods: A total of 16 patients with carcinoma in situ refractory to bacillus Calmette-Guerin were enrolled in a phase I, open label, single institution study. A minimum of 3 eligible patients were included per dose level. Paclitaxel-hyaluronic acid solution (ONCOFID-P-B™) was administered for 6 consecutive weeks. The primary objective was to identify the maximum tolerated dose and the recommended dose. As secondary objectives the safety profile of ONCOFID-P-B, the pharmacokinetic profile after each instillation and the tumor response were also evaluated. Results: No dose limiting toxicity occurred at any drug level evaluated. The plasma levels of the study drug were always below the lower limit of quantification at all tested doses after each instillation. A total of 11 adverse events were reported by 7 patients and 9 (60%) showed complete treatment response. Conclusions: Intravesical instillation of ONCOFID-P-B for carcinoma in situ refractory to bacillus Calmette-Guerin showed minimal toxicity and no systemic absorption in the first human intravesical clinical trial to our knowledge. Finally, satisfactory response rates were observed.

Grid management has always been a complex issue, especially when Grids are composed of a large number of resources and the efficiency is a key aspect (e.g to support applications with QoS requirements). For this, Grid administration becomes increasingly important, and advanced instrumentation for Grid management is needed. In this chapter we present GridWalker, a visual application that allows the efficient management of information about the resource characteristics and their updated status, in order to foster a proper allocation of user jobs on available resources.

Background and Aim: Renal cell carcinoma (RCC) is the 13th most common cancer worldwide and accounts for 4% of all adult malignancies. Herein the state of the art and recent advances in cross-sectional radiological imaging applied to RCC are reviewed, including ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography. Methods: Literature search of peer-reviewed papers published by October 2010. Results: In front of more conventional and widespread imaging tools, such as ultrasonography and computed tomography, an array of newer and attractive radiological modalities are under investigation and show promise to improve our ability to noninvasively detect renal tumors and its recurrences, accurately assess the extent of the disease, and reliably evaluate treatment response, particularly in the era of antiangiogenetic therapy. Conclusions: Recent major advances in radiological imaging techniques have considerably improved our ability to diagnose, stage and follow-up RCC. Further studies are needed to evaluate the potential of most recent and still investigational imaging tools.

Advances in imaging have an increasingly significant role in the diagnosis, staging and restaging of patients with bladder cancer. This paper reviews the current use of imaging in bladder neoplasms, comparing the different radiologic investigations, and discusses the potential applications of novel imaging techniques in the management of patients with bladder cancer.

Current grid resource management tools provide sufficient support for jobs executed in batch or "best-effort" modes, but are not adequate for jobs with demanding quality of service requirements, like jobs with time constraints. For such class of applications, missing the required deadline can have unpredictable consequences, from loss of quality to inconsistent results. In this chapter we present SoRTGrid, a grid framework that provides a set of services and features to discover and manage resources for soft real-time jobs. SoRTGrid is based on a direct comparison of the application requirements with the available resource offers and relies on a distributed Bid repository coupled with an overlay grid architecture.

Objective: The aim of this work was to verify the tolerability and the preliminary clinical results of intensive intravesical instillations of a mitomycin C (MMC) regimen. Patients and Methods: From September 2007 to November 2009, 40 consecutive evaluable patients with pathologically confirmed intermediate-risk non-muscle-invasive bladder cancer (NMIBC) were enrolled after complete transurethral resection of all visible tumors. The mean age of the patients was 64.5 years. 40 mg MMC diluted in 50 ml of saline was instilled in the bladder three times a week for 2 weeks. The median follow-up was 9 months. Results: All patients fulfilled the scheduled treatment. The local adverse events seen were negligible, while no significant deviation from normal values was observed in blood counts for each patient. Twenty-three of 40 patients (57.5%) showed negative at the cystoscopic control which was performed every 3 months with normal spontaneous and washing cytological exams. Conclusion: MMC is a well-known chemotherapeutic agent for the intravesical therapy of NMIBC. With a view to improving its results, we changed the frequency and intensity of the instillations. No significant local or systemic toxicity was reported. Intensive intravesical instilllations of MMC might become a tool in the management of NMIBC.

Non muscle invasive bladder cancer, given its high tendency to recur, coupled with an ever-present possibility to progress to potentially life-threatening muscle-invasive disease, remains a challenging clinical problem. Optimal management begins with early detection and accurate risk assessment through careful attention to clinical and histology features. Prevention of recurrence requires the sequential application of tools to completely remove all visible disease, avert reimplantation during surgical resection, ablate microscopic foci and prevent the emergence of new primary tumors amidst a field of carcinogen-exposed urothelium. Previously standard adjunctive intravesical chemo-immunotherapies are obtaining new vitality as optimization strategies, while new drugs and rational drug combinations provide the potential for improved efficacy with reduced toxicity. Novel therapeutic modalities under investigation include activation of the host immune system and enhancement of the cytotoxic effects of chemotherapeutic agents. New technological advances such as microwave chemothermotherapy offer further hope for better outcomes even for disease previously refractory to conservative measures. While much of this research is in the preclinical phase, the encouraging results of many of the studies discussed here suggest that testing in human trials should follow in the coming years. Yet despite these advances, aggressive surgical management involving bladder removal continues to be an indispensable life-saving maneuver that must be considered in all high-risk cases that fail to promptly respond to other measures. Although great strides continue to be made each year in the diagnosis and management of bladder cancer considerably more work needs to be done in order to improve the lives of our patients with this disease.

Due to their complexity, the exploitation of Grid environments is not a trivial activity for many users, and a key factor is to enable a simplified and transparent orchestration of resources and jobs. Particularly critical is the deployment of matching procedures capable to effectively meet user's requirements with resources offer. We introduce GREEN a management tool primarily devoted to the matchmaking process, based on a performance characterization of both resources and job requirements. Leveraging on a two-level benchmarking methodology, GREEN allows users to express performance preference through an appropriate extension to Grid submission and description languages such as JSDL and Glue. Operating at intermediate level between applications and Grid middleware, GREEN reduces the gap between users' needs and available resources thus enabling a seamless exploitation of the Grid.

Grids enable the creation of virtual laboratories for the collaborative use of\break sophisticated instruments producing large amount of data that have to be processed in order to extract knowledge. In this context, a very important task is related with image processing, since most of the data are images that have to be adequately analyzed. We present a Grid-aware version of the Parallel IMAGE processing GEnoa library (PIMA(GE)2 Lib). The major features of our approach are the preservation of the ease in the development of parallel image processing applications and the possibility to efficiently exploit the Grid resources for their executions. The resulting tool, called PIMA(GE)2 Grid, is based on the Grid Service technology; from the user point of view, it acts as an intermediate layer between Grid resources and parallel image processing applications. PIMA(GE)2 Grid represents a feasible solution to exploit multiple and computationally intensive image processing applications in a virtual laboratory.

The merging between molecular biology and computer science is becoming a key point in knowledge discovery, in particular when huge amount of data coming from different laboratories need to be integrated and analyzed For example Tissue MicroArray (TMA) is a high throughput technology that allows researchers to analyze several tissue samples in a parallel way. TMA is a good validation method of researcher's hypothesis about pathological tissue morphology and biomarkers evaluation. In this context, the Grid technology is a good opportunity to share data and solve intensive storage and computing problems. However, the exploitation of the Grid is not a trivial pursuit for many users. Nowadays, an important issue is to provide a simplified use of Grid resources, enabling the use of tools that scientists usually employ. In this paper, we present TMA inspect, a Web based system for Tissue Microarray experiment analysis that provides to not expert users a graphical interface to search for TMA images and to efficiently process them in EGEE. For the image elaboration we use PIMA(GE)(2) Lib, the Parallel IMAGE processing GEnoa Library.

The grid represents a great opportunity in the scientific community to solve data/compute intensive problems and to share data. Using the grid, different application domains could achieve great advantages; however, the exploitation of the grid is not a trivial pursuit for many users. The key issue is to enable a simplified use of grid resources and tools that scientists usually employ. In this paper, we investigate these topics in bioinformatics community to allow the efficient elaboration on the grid of images obtained through the tissue microarray technique. We present a grid framework for tissue microarray analysis, GF4TMA, that allows the selection of TMA images and their efficient analysis by the exploitation of the grid architecture. In particular, we exploited PIMA(GE)2 Lib, the Parallel IMAGE processing GEnoa Library. A critical point was to enable parallel computations on the grid without compromising the efficiency and the user-friendliness of the native library. We tackled this issue by encapsulating the library in a grid service.

Voronoi diagrams and Delaunay triangulations are gaining attention in several P2P applications managing a wide number of distributed and mobile entities, from resource discovery in auction-like networks to the realization of networked virtual environments. In this paper we consider a scalable partitioning technique of the entity space based on Voronoi diagrams, useful for a wide variety of distributed applications that exhibit a dynamically changing topology. Using the HyVonNe (hybrid Voronoi network) architecture, the space is partitioned in Voronoi regions, each one including a limited number of entities and managed by a region leader, that are created and deleted depending on the spatial density of such entities, while the Delaunay triangulation connecting the region leaders is used to support the partitioning, routing and searching activities. The resulting two-layers structure (entity space and Voronoi regions) is scalable and extendable, allows to reduce the propagation of the entity position updates in the network and to maintain the load balancing among regions. Simulation results related to two different application fields are presented.

To evaluate the costs of bladder bladder cancer treatment and follow-up.A purely economic analysis was carried out evaluating in our Institution a) the cost of an hospital stay of patients submitted to transurethral resection of superficial bladder cancer and to radical cystectomy for invasive bladder cancer, b) the cost of endovesical immuno-chemotherapy performed as day hospital regimen, c) the cost of the first year of follow-up according to European Association of Urology's Guidelines as outpatient regimen.The total cost related to a superficial tumour of the bladder treated with an endoscopic resection amounts to Euro 2,242.20, while in case of invasive bladder cancer treated with a radical cystectomy it comes to Euro 6,860. For chemo-immunotherapy the costs in a day hospital regimen related to a 8-weekly session of mitomicin, 6-weekly session of epirubicin and BCG are Euro 1,420, Euro 1,037 and Euro 975, respectively. The first year of follow-up for a patient with low risk of superficial bladder cancer without recurrence costs Euro 265.15. In case of high risk superficial bladder cancer the cost reaches Euro 321.75. In case of a patient with invasive bladder cancer in the first year, when follow-up is more strict, expenses amount to Euro 548.90.Cancer bladder is a high-cost illness due, in particular, to its heterogeneity in presentation and high rate of recurrences which makes any evaluation underestimated. The possibility of containing costs is essentially related to optimization of the follow-up and to the development of optimal therapeutic procedures which could lead to a reduction in the number of recurrences.

The Tissue MicroArray (TMA) technique is assuming even more importance. Digital images acquisition becomes fundamental to provide an automatic system for subsequent analysis. The accuracy of the results depends on the image resolution, which has to be very high in order to provide as many details as possible. Lossless formats are more suitable to bring information, but data file size become a critical factor researchers have to deal with. This affects not only storage methods but also computing times and performances. Pathologists and researchers who work with biological tissues, in particular with the TMA technique, need to consider a large number of case studies to formulate and validate their hypotheses. It is clear the importance of image sharing between different institutes worldwide to increase the amount of interesting data to work with. In this context, preserving the security of sensitive data is a fundamental issue. In most of the cases copying patient data in places different from the original database is forbidden by the owner institutes. Storage, computing and security are key problems of TMA methodology. In our system we tackle all these aspects using the EGEE (Enabling Grids for E-sciencE) Grid infrastructure. The Grid platform provides good storage, performance in image processing and safety of sensitive patient information: this architecture offers hundreds of Storage and Computing Elements and enables users to handle images without copying them to physical disks other than where they have been archived by the owner, giving back to end-users only the processed anonymous images. The efficiency of the TMA analysis process is obtained implementing algorithms based on functions provided by the Parallel IMAge processing Genoa Library (PIMA(GE)2 Lib). The acquisition of remotely distributed TMA images is made using specialized I/O functions based on the Grid File Access Library (GFAL) API. In our opinion this approach may represent important contribution to tele-pathology development.

Surface characterization of molecules may provide useful information about their functionalities and potential interactions with other molecules. Even if many algorithms and tools for the protein surface modeling were proposed, presently a suitable and efficient system that enables wide range analysis of the protein external morphology does not exists. In this paper we present a parallel workflow for the reconstruction of molecular surfaces based on a set of grid services. The aim is to provide scientists to get easily and quickly an accurate surface representation of the molecules made available in the protein data bank. The system front end is represented by a Java application, that is responsible to manage the computation on the basis of the parameters specified by the user. Furthermore, the application permits to directly visualize the resulting molecular surface and to download it on the user machine. The modular approach we propose allows in perspective the extensibility of the system through the integration of further grid services, in order to perform even more complex surface analyses in the grid environment.

We present a Grid-aware application for the extraction of isosurfaces from volumetric data sets. This is an important issue in the design of a virtual laboratory since it permits to analyze data produced by different types of scientific instruments. After a short description of the basic functionalities we focus on the issues for the efficient use of Grid resources. Our implementation is designed following a Grid service approach and adopts Globus Toolkit 4 as middleware. The main advantages of the use of the Grid are the possibility of processing huge data sets and of satisfying more requests simultaneously.

The latest Globus Toolkit 4 (GT4) version, fully OGSA compliant and almost completely based on Grid Services, is expected to become the reference version of the Globus Toolkit Therefore, the necessity to migrate from previous versions, especially the widespread GT2, to GT4 is becoming a relevant issue for many Grid systems. We present a migration experience from GT2 to GT4 of a simple tool for resource discovery and selection, and execution of parallel applications in a computational Grid environment. The proposed tool provides a simple and intuitive user interface, a structured view of Grid resources, a simple mechanism for resource selection, and support for application staging and execution. We discuss some relevant differences between GT2 and GT4, particularly for the Monitoring and Discovering subsystem GT4 turns out to be more powerful and flexible. Just because we address the implementation of basic functionalities, the proposed discussion may be of general interest.

From A critical assessment of text mining methods in molecular biology, [Background] Within the emerging field of text mining and statistical natural language processing (NLP) applied to biomedical articles, a broad variety of techniques have been developed during the past years. Nevertheless, there is still a great ned of comparative assessment of the performance of the proposed methods and the development of common evaluation criteria. This issue was addressed by the Critical Assessment of Text Mining Methods in Molecular Biology (BioCreative) contest. The aim of this contest was to assess the performance of text mining systems applied to biomedical texts including tools which recognize named entities such as genes and proteins, and tools which automatically extract protein annotations., [Results] The "sentence sliding window" approach proposed here was found to efficiently extract text fragments from full text articles containing annotations on proteins, providing the highest number of correctly predicted annotations. Moreover, the number of correct extractions of individual entities (i.e. proteins and GO terms) involved in the relationships used for the annotations was significantly higher than the correct extractions of the complete annotations (protein-function relations)., [Conclusion] We explored the use of averaging sentence sliding windows for information extraction, especially in a context where conventional training data is unavailable. The combination of our approach with more refined statistical estimators and machine learning techniques might be a way to improve annotation extraction for future biomedical text mining applications., This work was sponsored by DOC, the doctoral scholarship programme of the Austrian Academy of Sciences and the ORIEL (IST-2001-32688) and TEMBLOR (QLRT-2001-00015) projects.

Image processing applications are computing demanding and since a long time much attention has been paid to the use of parallel processing. Emerging distributed and Grid based architectures represent new and well suited platforms that promise the availability of the required computational power. In this direction image processing has to evolve to heterogeneous environments, and a crucial aspect is represented by the interoperability and reuse of available and high performance code. This paper describes our experience in the development of PIMA(GE)2, Parallel IMAGE processing GEnoa server, obtained wrapping a library using the CORBA framework. Our aim is to obtain a high level of flexibility and dynamicity in the server architecture with a possible limited overhead. The design of a hierarchy of image processing operation objects and the development of the server interface are discussed.

Publisher Summary This chapter discusses the parallel decimation of 3d meshes for efficient web-based isosurface extraction. Isosurface extraction is a basic operation that permits to implement many type of queries on volumetric data. The result of a query for a particular isovalue is a triangulated irregular network (TIN) that may contain huge number of points and of triangles, depending on the size of the original data set. In distributed environment, due to the limits of bandwidth availability and/or to the characteristics of the client, it may be necessary to visualize the result of the query with lower resolution. The simplification process is costly, especially for huge data sets. The problem of efficiently parallelize this process is discussed using a cluster of COTS (commercial, off-the-shelf) PCs for a Web-based parallel isosurface extraction system. The advantages of this approach are due to the minimization of the communications number and size between processes and the reduction of the sequential part of the algorithm.

In this paper we present a parallel algorithm, implemented using MPICH, for isosurface extraction from volumetric data sets. The main contribution of this paper is in the analysis and performance improvements of the different phases of the isosurface production process including computation and output generation. The resulting algorithm is particularly well suited for online applications and for remote results visualization.

Pioneering drugs for overactive bladder and detrusor overactivity: Ongoing research and future directions

Mobile hosts of ad-hoc networks operate on battery, hence optimization of system lifetime, intended as maximization of the time until the first host drains-out its battery, is an important issue. Some routing algorithms have already been proposed, that require the knowledge of the future behavior of the system, and/or complex routing information. We propose a novel routing algorithm that allows each host to locally select the next routing hop, having only immediate neighbor information, to optimize the system lifetime. Simulation results of runs performed in different scenarios are finally shown.

Ecological speciation has become a popular model for the development and maintenance of reproductive isolation in closely related sympatric pairs of species or ecotypes. An implicit assumption has been that such pairs originate (possibly with gene flow) from a recent, genetically homogeneous ancestor. However, recent genomic data have revealed that currently sympatric taxa are often a result of secondary contact between ancestrally allopatric lineages. This has sparked an interest in the importance of initial hybridization upon secondary contact, with genomic reanalysis of classic examples of ecological speciation often implicating admixture in speciation. We describe a novel occurrence of unusually well-developed reproductive isolation in a model system for ecological speciation: the three-spined stickleback (Gasterosteus aculeatus), breeding sympatrically in multiple lagoons on the Scottish island of North Uist. Using morphological data, targeted genotyping, and genome-wide single-nucleotide polymorphism data, we show that lagoon resident and anadromous ecotypes are strongly reproductively isolated with an estimated hybridization rate of only ∼1%. We use palaeoecological and genetic data to test three hypotheses to explain the existence of these species-pairs. Our results suggest that recent, purely ecological speciation from a genetically homogeneous ancestor is probably not solely responsible for the evolution of species-pairs. Instead, we reveal a complex colonization history with multiple ancestral lineages contributing to the genetic composition of species-pairs, alongside strong disruptive selection. Our results imply a role for admixture upon secondary contact and are consistent with the recent suggestion that the genomic underpinning of ecological speciation often has an older, allopatric origin.

We performed a search for eclipsing and dipping sources in the archive of the EXTraS project - a systematic characterization of the temporal behaviour of XMM-Newton point sources. We discovered dips in the X-ray light curve of 3XMM J004232.1+411314, which has been recently associated with the hard X-ray source dominating the emission of M31. A systematic analysis of XMM-Newton observations revealed 13 dips in 40 observations (total exposure time $\sim$0.8 Ms). Among them, four observations show two dips, separated by $\sim$4.01 hr. Dip depths and durations are variable. The dips occur only during low-luminosity states (L$_{0.2-12}, 11 pages, 2 figures, 5 tables, accepted for publication in ApJL