Search

Background: We investigated the impact of PIK3CA and TP53 mutations and p53 protein status on the outcome of patients who had been treated with adjuvant anthracycline-taxane chemotherapy within clinical trials in the pre- and post-trastuzumab era. Results: TP53 and PIK3CA mutations were found in 380 (21.5%) and 458 (25.9%) cases, respectively, including 104 (5.9%) co-mutated tumors; p53 immunopositivity was observed in 848 tumors (53.5%). TP53 mutations (p < 0.001) and p53 protein positivity (p = 0.001) were more frequent in HER2-positive and triple negative (TNBC) tumors, while PIK3CA mutations were more frequent in Luminal A/B tumors (p < 0.001). TP53 mutation status and p53 protein expression but not PIK3CA mutation status interacted with trastuzumab treatment for disease-free survival; patients with tumors bearing TP53 mutations or immunopositive for p53 protein fared better when treated with trastuzumab, while among patients treated with trastuzumab those with the above characteristics fared best (interaction p = 0.017 for mutations; p = 0.015 for IHC). Upon multivariate analysis the above interactions remained significant in HER2-positive patients; in the entire cohort, TP53 mutations were unfavorable in patients with Luminal A/B (p = 0.003) and TNBC (p = 0.025); p53 immunopositivity was strongly favorable in patients treated with trastuzumab (p = 0.009). Materials and Methods: TP53 and PIK3CA mutation status was examined in 1766 paraffin tumor DNA samples with informative semiconductor sequencing results. Among these, 1585 cases were also informative for p53 protein status assessed by immunohistochemistry (IHC; 10% positivity cut-off). Conclusions: TP53 mutations confer unfavorable prognosis in patients with Luminal A/B and TNBC tumors, while p53 immunopositivity may predict for trastuzumab benefit in the adjuvant setting.

PURPOSE: Exercise training programs improve microcirculatory alternations in patients with chronic heart failure (CHF). However less is known about the acute effect of maximum exercise on the skeletal muscle microcirculation. We aimed to assess the effect of acute exercise on peripheral microcirculation of patients with CHF, as assessed by near-infrared spectroscopy with vascular occlusion technique. METHODS: Tissue oxygenation was evaluated in 8 stable patients with CHF (7 males; mean age, 60) 9 years; body mass index, 26.3) 3.8 kg/m2 ) and 8 healthy subjects (matched for age, sex, and body mass index) before and after cardiopulmonary exercise testing. Tissue oxygen saturation (StO 2 ), StO 2peak , oxygen consumption rate, and endothelial function (reperfusion rate), before and after maximum exercise, were assessed. RESULTS: Patients with CHF had lower StO 2 and reperfusion rate compared with healthy subjects (71.4%) 9.8% vs 81.0%) 5.4% and 9) 1 %/min vs 13.9) 5.8%/min, respectively; P < .05) at rest. Oxygen consumption rate increased after exercise in patients with CHF and healthy subjects (from - 31.7) 8.2 to - 43.7) 12.7 and from - 35.7) 6.7 to - 42.4) 6.4, respectively; P < .05). StO2decreased significantly after maximal exercise in patients with CHF (from 71.4) 9.8 to 65.2) 12.7; P < .05), whereas it returned to the preexercise values in healthy subjects (from 81.0) 5.4 to 80.3) 7.0). There was a significant between-group difference ( P < .05). CONCLUSIONS: Patients with CHF present microcirculatory alternations. Acute exercise exerts an effect on microcirculation in peripheral, nonexercising muscles, with altered response in patients with CHF compared with healthy subjects. Copyright © 2016 Wolters Kluwer Health, Inc.

Attribute grammars (AG) allow the addition of context-sensitive properties into context free grammars, augmenting their expressional capabilities by using syntactic and semantic notations, making them in this way a really useful tool for a considerable number of applications. AGs have extensively been utilized in applications such as artificial intelligence, structural pattern recognition, compiler construction and even text editing. Obviously, the performance of an attribute evaluation system resides in the efficiency of the syntactic and semantic subsystems. In this paper, a hardware architecture for an attribute evaluation system is presented, which is based on an efficient combinatorial implementation of Earley's parallel parsing algorithm for the syntax part of the attribute grammar. The semantic part is managed by a special purpose module that traverses the parse tree and evaluates the attributes based on a proposed stack-based approach. The entire system is described in Verilog HDL (hardware design language), in a template form that given the specification of an arbitrary attribute grammar, the HDL synthesizable source code of the system is produced on the fly by a proposed automated tool. The generated code has been simulated for validation, synthesized and tested on an Xilinx FPGA (field programmable gate arrays) board for various AGs. Our method increases the performance up to three orders of magnitude compared to previous approaches, depending on the implementation, the size of the grammar and the input string length. This makes it particularly appealing for applications where attribute evaluation is a crucial aspect, like in real-time and embedded systems. Specifically, a natural language interface is presented, based on a question-answering application from the area of airline flights.

This paper presents a highly efficient architecture for the hardware implementation of context-free grammar (CFG) parsers. Its efficiency stems from an innovative combinatorial circuit that implements the fundamental operation of Earley's parsing algorithm in time complexity O(log"2|G|), where |G| is the size of the CFG. Using this hardware architecture in a template form, we have developed an automated synthesis tool that, given the specification of an arbitrary CFG, generates the HDL (Hardware Design Language) synthesizable source code of the hardware parser for the given grammar. The generated source has been simulated for validation, synthesized and tested on a Xilinx FPGA (Field Programmable Gate Array) board. Our method increases the performance by a factor of one to two orders of magnitude, compared to previous hardware implementations, depending on the size of the grammar and the input string length. The speedup, compared to the pure software implementation, varies from two orders of magnitude for toy-scale grammars to six orders of magnitude for large real life grammars. This makes it particularly appealing for applications where (syntactic) pattern recognition response is a crucial aspect.

The Future Internet (FI) era dictates the deployment of high complexity systems having a variety of properties such as adaptivity, self configuration and self optimization. This paper discusses on the design and deployment of an autonomic management framework, targeting real-time optimization of operational properties in a smart building cognitive environment. The architecture of an autonomous smart building system is described, focusing on diverse requirement satisfaction, including response time, energy efficiency and users' satisfaction. The main systems' components are introduced along with a indicative operation scenario that demonstrates multi — criticality issues explored. The scope of the paper is a) to point out challenges in building an autonomic smart building environment to support multi-critical applications and b) to indicate efficient solutions for dealing with them, promoting self-configuration and self-optimisation properties.

Purpose: Continuous therapy (CT) prolongs progression-free survival 1 (PFS1; time from random assignment until the first progression or death), but chemotherapy-resistant relapse may negatively impact overall survival (OS). Progression-free survival 2 (PFS2; time from random assignment until the second progression or death) may represent an additional tool to estimate outcome. This study evaluates the benefit of novel agent-based CT versus fixed duration of therapy (FDT) in patients with newly diagnosed myeloma. Methods: We included patients enrolled onto three phase III trials that randomly assigned patients to novel agent-based CT versus FDT. Primary analyses were restricted to the intent-to-treat population eligible for CT (patients progression free and alive at 1 year after random assignment). Primary end points were PFS1, PFS2, and OS. All hazard ratios (HRs) and 95% CIs were adjusted for several potential confounders using Cox models. Results: In the pooled analysis of the three trials, 604 patients were randomly assigned to CT and 614 were assigned to FDT. Median follow-up was 52 months. In the intent-to-treat CT population, CT (n = 417), compared with FDT (n = 410), significantly improved PFS1 (median, 32 v 16 months, respectively; HR, 0.47; 95% CI, 0.40 to 0.56; P < .001), PFS2 (median, 55 v 40 months, respectively; HR, 0.61; 95% CI, 0.50 to 0.75; P < .001), and OS (4-year OS, 69% v 60%, respectively; HR, 0.69; 95% CI, 0.54 to 0.88; P = .003). Conclusion: In this pooled analysis, CT significantly improved PFS1, PFS2, and OS. The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission. PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.

The Hippocratic Collection, including the most of ancient Greek medicine, remains still interesting, despite the recent advances that transformed definitely the urological healing methods. Considering the patient as a unique psycho-somatic entity and avoiding high risk surgical manipulations were the leading principles dictating the everyday practice. Contemporary physicians can still learn from the clinical observations in times of complete absence of laboratory or imaging aid, from the prognostic thoughts, the ethics, and the philosophical concepts, represented by the Hippocratic writings, tracing into them the roots of Rational Medicine in general and Urology in particular.

Purpose:: We report the continence status and urodynamic findings in 59 patients who underwent radical cystectomy and orthotopic bladder reconstruction using a modified S-ileal neobladder technique between January 1993 and July 2002.Materials and Methods:: Continence status was assessed using patient interview, frequency-volume charts and the need for protective devices. Reservoir sensation, compliance, capacity and activity were assessed by enterocystometry. Post-void residual urine volume greater than 100 ml was the indication for clean intermittent self-catheterization.Results:: Daytime continence was reported by 95.5% and 100% of our patients at 1 and 5 years, respectively. Overall, 77.7% of patients reported nighttime continence at 1 year and 96.5% at 5 years. The need for a protective device decreased with time and most of the patients would have undergone the operation again. Enterocystometric capacity and maximum reservoir pressure remained remarkably stable at 391.6 versus 440 ml, and 30 ...

Objective: To determine the efficacy and safety of two different doses of intravesical mitoxantrone and of recombinant interferon-α (IFNα-2b), instilled after transurethral resection (TUR) of superficial transitional cell carcinoma (TCC) of the bladder. Material and Methods: 208 patients (mean age 62.05 years) with primary or recurrent superficial (TaG1, T1G1, T1G2) bladder cancer were randomly allocated into four groups, after TUR of all visible tumors. Group A (45 patients) received no further therapy; group B (56 patients) received 10 mg of mitoxantrone (6 weekly and 20 fortnightly instillations), group C (54 patients) 20 mg of mitoxantrone (3 fortnightly and 10 monthly instillations) and group D (53 patients) received 100 MU of IFNα-2b (8 weekly, 8 fortnightly and 6 monthly instillations). Results: During the follow-up (mean 21.09 months), 29 (64.44%) patients in group A had recurrence, compared with 19 (33.92%) in group B, 17 (31.48%) in group C and 15 (28.3%) patients in group D (p < 0.005). Furthermore, the differences in simple recurrence rates were statistically more significant (p < 0.05), when group A was compared with the three other groups in the terms of T1G2, recurrent and multiple neoplasms. Twenty-nine patients (10, 7, 8, and 4 in groups A–D) experienced tumor progression, and the differences between the four groups were not statistically significant (p > 0.05). The mean recurrence time was 9.03 months in group A, 13.74 in group B, 14.24 in group C and 17.4 months in group D (p < 0.001), and the recurrence rate per 100 patient-months was 4.39, 1.57, 1.48 and 1.06, respectively (p < 0.05). Toxicity (grade 1–3) was recorded in 23.21% in group B, in 31.48% in group C and in 9.43% in group D (p < 0.01). Conclusion: The two doses of mitoxantrone resulted in similar efficacy for the prevention of superficial bladder cancer recurrences, with the dose of 10 mg of mitoxantrone being related to fewer side effects. In comparison with mitoxantrone, the adjuvant intravesical immunotherapy with 100 MU of IFNα-2b showed a better combination of efficacy and safety.

In this paper, a platform is presented, that given a Stochastic Context-Free Grammar (SCFG), automatically outputs the description of a parser in synthesizable Hardware Description Language (HDL) which can be downloaded in an FPGA (Field Programmable Gate Arrays) board. Although the proposed methodology can be used for various inexact models, the probabilistic model is analyzed in detail and the extension to other inexact schemes is described. Context-Free Grammars (CFG) are augmented with attributes which represent the probability values. Initially, a methodology is proposed based on the fact that the probabilities can be evaluated concurrently with the parsing during the parse table construction by extending the fundamental parsing operation proposed by Chiang & Fu. Using this extended operation, an efficient architecture is presented based on Earley’s parallel algorithm, which given an input string, generates the parse table while evaluating concurrently the probabilities of the generated dotted grammar rules in the table. Based on this architecture, a platform has been implemented that automatically generates the hardware design of the parser given a SCFG. The platform is suitable for embedded systems applications where a natural language interface is required or in pattern recognition tasks. The proposed hardware platform has been tested for various SCFGs and was compared with previously presented hardware parser for SCFGs based on Earley’s parallel algorithm. The hardware generated by the proposed platform is much less complicated than the one of comparison and succeeds a speed-up of one order of magnitude.

Background: Melphalan is one of the most active chemotherapeutic agents in the treatment of multiple myeloma (MM). However, the mechanism underlying differential patient responses to melphalan therapy is unknown. Methods: Chromatin structure, transcriptional activity and DNA damage response signals were examined following ex vivo treatment with melphalan of both malignant bone marrow plasma cells (BMPCs) and peripheral blood mononuclear cells (PBMCs) of MM patients, responders (n = 57) or non-responders (n = 28) to melphalan therapy. PBMCs from healthy controls (n = 25) were also included in the study. Results: In both BMPCs and PBMCs, the local chromatin looseness, transcriptional activity and repair efficiency of the transcribed strand (TS) were significantly higher in non-responders than in responders and lowest in healthy controls (all P

In our multicenter retrospective analysis in 186 patients with metastatic renal cell carcinoma (mRCC) and synchronous metastases treated with sunitinib, we examined the role of cytoreductive nephrectomy (CN) in this clinical setting. CN proved to have a beneficial prognostic effect in survival independent of other diseaseor patient-related factors. CN remains a reasonable option for mRCC patients scheduled to be treated with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs). Introduction/Background: The aim of this study was to evaluate the prognostic role of CN in patients with mRCC and synchronous metastases treated with the VEGF receptor TKI, sunitinib. Patients and Methods: Patients with a diagnosis of metastases before, at the time of, or within 3 months from the diagnosis of renal cell carcinoma (RCC) and first-line treatment with sunitinib were included. Baseline characteristics were correlated with overall survival (OS) according to hazard ratios estimated from univariate Cox proportional hazards models. Significant factors were then included in a multivariate Cox proportional hazards model. Results: One hundred eighty-six patients treated between January 2006 and March 2012 were selected. Thirty-six (19%) had not undergone CN. CN was offered to younger patients with better prognoses. Patients who underwent CN lived significantly longer than patients without CN (median OS, 23.9 [95% confidence interval (CI), 20.8-28.8] vs. 9 [95% CI, 4-16.4] months; P < .001). Multivariate analysis showed that CN had an independent prognostic significance. No specific subgroup benefiting from CN was identified. Conclusion: CN was an independent favorable prognostic factor in patients with synchronous metastases from RCC, treated with sunitinib. Information regarding the selection of mRCC patients likely to benefit from CN might be derived by ongoing phase III trials. © 2014 Elsevier Inc. All rights reserved.

We prospectively evaluated the effect of bortezomib, thalidomide and dexamethasone (VTD) consolidation on bone metabolism of 42 myeloma patients who underwent an autologous stem cell transplantation (ASCT). VTD started on day 100 post ASCT; patients received four cycles of VTD (first block), were followed without treatment for 100 days and then received another four VTD cycles (second block). During this 12-month period, bisphosphonates were not administered. Best response included stringent complete remission (sCR) in 15 (35.7%) patients, complete response (CR) in 13 (30.9%), vgPR in 7 (16.6%), PR in 4 (9.5%), while 3 (7.1%) patients developed a progressive disease (PD). Importantly, 33.3% and 47.6% of patients improved their status of response after the first and second VTD block, respectively. VTD consolidation resulted in a significant reduction of circulating C-terminal cross-linking telopeptide of collagen type I (CTX), soluble receptor activator of the nuclear factor-kappa B ligand (sRANKL) and osteocalcin (OC), whereas bone-specific alkaline phosphatase (bALP) remained stable compared with pre-VTD values. During the study period, only one patient with a PD developed a skeletal-related event (that is, radiation to bone). The median time to progression (TTP) after ASCT was 34 months and the median time of next treatment was 40 months. We conclude that VTD consolidation post ASCT reduces bone resorption and is associated with a very low incidence of skeletal-related events (SREs) despite the absence of bisphosphonates; the later do not appear to be necessary in this context. © 2014 Macmillan Publishers Limited.

Purpose: We evaluated, in vivo, the effect of ionising radiation on the angiogenesis process in the chick embryo and its chorioallantoic membrane (CAM) using digital subtraction angiography (DSA) in conjunction with computer-assisted image analysis. Information regarding the ionising effect on endothelial cells during radiation treatment was extracted. Material and Methods: Two series of fertilized eggs were irradiated with a single ionising radiation dose of 10 Gy on days 9 and 13 of embryonic development. Angiography was carried out 24 h after irradiation. The angiographic images were digitized and subsequently processed. A set of specific morphological parameters was defined to allow an analytical characterization of the vascularity status. Vessels were classified into three categories according to their diameters (≥200 μm, 100-200 μm and 50-100 μm). The data were normalized and statistically evaluated. Results: On day 10, total vascular area and total vascular length presented a 15.6±1.2% and 18.4±2.4% reduction, respectively, while vascular diameters increased 3.3±0.5%. The vessel area and length of the first category (≥200 μm) increased 9.8±1.1% and 8.1±0.9%, respectively, while these morphometric parameters for each of the remaining two categories decreased 44.3±2.9%, 38.7±4.2% and 45±3.8%, 30.7±3.4%, respectively. On day 14 insignificant changes were observed. Conclusion: Computerised analysis of angiographic images showed that the antiangiogenic effect of irradiation during the various phases of CAM development is larger on the 10th day than that observed on day 14 and it depends on the vessel size.

In optically transparent wavelength-division-multiplexed (WDM) networks, sudden variations in the number of propagating wavelengths generate optical-power transients that can degrade the transmission performance of the surviving wavelength channels. Computer simulation is employed to study the effect of wavelength-number variations, caused by wavelength switching and cable cuts, on the transmitted wavelength channels in a long-haul WDM trunk-and-branch network. The transmission degradation of the affected channels is expressed in terms of Q-factor penalty, which reflects their optical power and optical-signal-to-noise ratio (OSNR) variations. Switching-induced wavelength power reductions are found to generate the largest penalties. It is shown that the Q-factor degradation is mostly caused by the receiver decision-threshold misalignment relatively to its optimum position and that the OSNR-dependent degradation is negligible. Therefore, receiver automatic gain control (ACC) can be used to suppress the signal. The AGC response should be much faster than in a conventional optically preamplified receiver to avoid error bursts. The time within which the Q-factor penalty reaches 1 dB is identified as the parameter that dictates the AGC response speed.

During a 3-year period, hundreds of patients underwent ESWL treatment with the Dornier HM-3 and HM-4 lithotriptors operating at our institution. Our experience in 3,500 patients treated with the HM-4 bath-free lithotriptor is reported. Patients with radiolucent or cystine stones, stones larger than 3 cm or staghorn calculi, multiple stones with a total burden of more than 3 cm and those not amenable to follow-up were excluded from the study. The overall stone-free rate was 70.7% and 81% at 1 and 3 months, respectively. The stone-free rates at 1 and 3 months were further determined by the exact location of each stone within the urinary tract. Stone-free rates at 3 months ranged from 90.84% for renal pelvic stones to 71.08% for lower calyceal stones, while the stone-free rates for ureteral calculi ranged from 80.85% for upper third unstented ureteral stones to 92.92% for lower ureteral stones. The overall complication rate was 6.02% with a 1.2% post-ESWL intervention rate (ureteroscopy or placement of percutaneous nephrostomy or stent).

Purpose: We determined and compared the presence and frequency of interferon-alpha 2b receptors in urothelial neoplasms and normal urothelium, since the biological activity of interferons becomes apparent only after they bind to specific receptors.Materials and Methods: With our method detection of interferon-alpha 2b receptors required a large number of cells, that is more than 1 x 106 cells per ml. We studied 14 patients with relatively large tumors of all stages and grades. Three patients had grade I, 4 grade II and 7 grade III disease. As controls we used biopsies of normal urothelium from 14 patients who underwent transvesical prostatectomy. Interferon-alpha 2b receptors were detected quantitatively through the binding of radiolabeled125 iodine human recombinant interferon-alpha 2b in normal and malignant urothelial tissue samples. The interferon-alpha 2b receptors are expressed as receptor sites per cell, and the results were evaluated with Scatchard analysis.Results: The number of interfero...

Background: Significant controversy exists in the literature regarding the role of pregnancy in the prognosis of breast cancer. We designed a matched case-case study, matching pregnancy-associated breast cancer (PABC) cases with breast cancer cases for stage, age, and year of diagnosis. Patients and Methods: 39 consecutive cases of PABC were matched with 39 premenopausal cases of breast cancer. Univariate and multivariate survival analyses followed by adjustment for stage, grade, estrogen receptor status, and age at diagnosis, were performed. Results: Regarding overall survival (OS), univariate analysis pointed to longer OS in non-PABC cases vs. PABC cases. Accordingly, a more advanced stage predicted shorter survival. In the multivariate analysis, the independent aggravating effect mediated by pregnancy persisted. Interestingly, a post hoc nested analysis within PABC cases indicated that the 3rd trimester pointed to shorter OS. The aforementioned results on OS were also replicated during the examination of relapse-free survival. Conclusion: Implementing a matched case-case design, the present study points to pregnancy as a poor prognostic factor for breast cancer. © 2013 S. Karger GmbH, Freiburg.

Central nervous system (CNS) involvement in patients with primary mediastinal large B-cell (PMLBCL) lymphoma is a rare event, occurring in approximately 6% of patients, on the basis of the review of the literature prior to induction of Rituximab. The aim of this retrospective study was to describe the incidence of CNS relapse among 100 consecutive patients with PMLBCL who were treated with R-CHOP±RT in comparison to patients treated with CHOP±RT (n=45) in 11 hospitals in Greece. Two patients experienced a CNS relapse, representing an overall frequency of 2.0% in R-CHOP treated patients and a 2-year actuarial incidence of 2.3%. Both patients had isolated CNS relapses. The incidence of CNS relapse after CHOP without Rituximab was 2/45 (4.4%) for a 2-year actuarial incidence of 7.5% (p=0.29). Again, both patients had isolated CNS relapses. Parenchymal-only localizations accounted for 3/4 cases. Risk factors for CNS involvement could include leukocytosis, poor performance status and higher age-adjusted International Prognostic Index, although their impact was weakened by competing risk survival analysis. Both patients relapsing after R-CHOP required CNS radiotherapy to achieve a complete remission and be forwarded to high-dose therapy and autologous stem cell transplantation: They are both alive and disease-free 18 and 23months after CNS relapse. Both cases relapsing after CHOP without Rituximab were salvaged by CNS radiotherapy (one also received intrathecal chemotherapy) entering long-term remissions. In conclusion, CNS relapses are rare in PMLBCL tending to be isolated in the CNS, probably reflecting the persistence of latent CNS disease than dissemination of resistant disease. The impact of Rituximab in reducing CNS relapses remains unknown. Established risk factors for CNS involvement in aggressive lymphomas may not be helpful in assessing the risk of CNS recurrence in this disease. Routine CNS prophylaxis is not probably required in PMLBCL. © 2012 John Wiley & Sons, Ltd.

The aim of our study is to determine the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) as a method of treatment of nephrolithiasis in childhood. Between 1986 and 1994, 50 children with renal calculi were treated by ESWL in our department. The age of the children ranged from 8 months to 14 years. Thirty-three of them were boys and 17 girls. The stone location was in the renal pelvis in 38 cases, in the upper renal calyx in 4 cases, in the lower calyx in 2, while 6 children had staghorn calculi. The stone size ranged between 3 and 39 mm. All treatments were performed with Dornier HM4 except 12 children, all older than 10 years, who underwent ESWL with Dornier HM3. All ESWL procedures took place under general anesthesia or sedation with ketamine. The number of shock waves varied between 400 and 2,000 per treatment and the standard maximum generator voltage was 18 kV. The overall stone clearance rate at 1 month was 66%. Fourteen children with large residual fragments underwent a second ESWL procedure 3 months later. With a mean follow-up of 33 months, 41 children (82%) are stone-free. Ten children developed urinary tract infection and 5 Steinstrasse. Twelve children had a pre- and post-ESWL DMSA scan and no permanent impairment of renal function was observed. We conclude that ESWL is the treatment of choice for urinary tract lithiasis in childhood. It is a low-risk method, without serious complications, which yields as high a success rate in children as in adults. We believe that as the stone fragmentation and clearance is much higher in children that in adults, the method must be the initial approach and may be the monotherapy even in staghorn or complex stones.

Objectives p53 tumor suppressor gene is considered to play a significant role in carcinogenesis. Mutations in the p53 are the most frequent genetic abnormalities encountered in human malignancies. Our aim was to investigate the expression of p53 oncoprotein in superficial and invasive transitional cell bladder cancer (TCC) as well as its correlation with established prognostic factors, such as histologic grade, tumor stage, DNA content, and survival. Methods Forty-five patients with superficial TCC (Ta-T1) and 42 with invasive TCC (T2-T4) were included in our study. Material from transurethral biopsy was examined using an immunohistochemical method and the monoclonal antibody Pab 1801. Results p53 tumor suppressor protein was overexpressed in 48.3% of TCC cases and more frequently in invasive than superficial TCCs ( P = 0.03) and undetectable in the tumor adjacent to normal tissue. p53 positivity was related to the degree of differentiation and with the stage of the disease of invasive TCCs ( P = 0.03 and P = 0.004, respectively), whereas no statistical significance was documented for superficial TCCs. Moreover, p53 overexpression demonstrated a statistical significance with DNA ploidy in superficial Ta-T1 tumors ( P = 0.04) and was suggestive in invasive T2-T4 tumors ( P = 0.08). There was no correlation of recurrence related to p53-positive superficial tumors ( P = 0.29). Patients with p53-positive invasive TCCs showed statistically significant worse survival ( P = 0.007), but in multivariate analysis, p53 positivity is not independently related to poor overall survival ( P = 0.30). When we combined ploidy and p53 status, we realized that the subset of patients with aneuploidy and p53 positivity had the worst prognosis ( P = 0.008). Conclusions The results suggest the involvement of p53 protein as a late event in bladder carcinogenesis. p53 does not seem to be a prognostic marker for recurrences of superficial tumors and is not independently related to survival. The aneuploidy of tumors correlates with the p53 positivity in bladder cancer. The combined expression of aneuploidy and p53 positivity in invasive tumors has strong association with the survival of patients.

In this paper a platform is presented, that given a stochastic context-free grammar (SCFG), automatically outputs the description of the parser in synthesizable hardware description language (HDL) which can be downloaded in an Field Programmable Gate Arrays (FPGA) board. Initially, according to our methodology the SCFG is augmented with attributes which store the probability values and can be evaluated through corresponding stack actions. The architecture of the produced system is based on a proposed extension of Earley’s parallel algorithm, which given an input string, generates the parse trees in the form of an AND-Or parse tree. This AND-or parse tree is then traversed using a proposed tree traversal technique in order to execute the corresponding actions in the correct order, so as to compute the necessary probabilities. The platform is suitable for embedded systems applications where a natural language interface is required or in pattern recognition tasks. The parser generated by the presented platform has been tested for various SCFGs and compared to software approaches. The performance comparison is one to two orders of magnitude in favor of the presented hardware, compared to previous software approaches, depending on the application, the input string length and the number of produced trees.

Epithelial differentiation antigens have been correlated with morphologic differentiation of neoplastic urothelium. Moreover, epidermal growth factor, which is a polypeptide regulating growth and differentiation of normal and neoplastic cells, is found in high concentrations in the urine while its receptors (EGFR) have been identified in bladder tumors. The aim of this study was to investigate the immunohistochemical expression of cytokeratin, epithelial membrane antigen (EMA), CEA and EGFR in transitional cell bladder carcinomas (TCC) and to define any correlation of their expression with tumor grade, stage and patient survival. Twenty-four biopsy specimens obtained from patients with TCC were studied retrospectively. There were 23 men and 1 woman with a mean follow-up of 64 months. Eight biopsy specimens, which represented tumor recurrences of 4 patients, were also included in our material. The immunohistochemical avidin-biotin complex method was performed on paraffin sections for the detection of cytokeratin and EGFR with monoclonal antibodies as well as CEA with a polyclonal antibody. Cytokeratin was detected in 83.5% of the TCC, EMA in 62% and CEA in 70%. The expression of the epithelial differentiation antigens in TCCs was heterogenous, showing an increased incidence in high-grade and high-stage TCC. The CEA expression in TCC demonstrated a statistically significant correlation with patient survival (p0.02). EGFR was detected in 50% of the TCC. Although not statistically significant, a trend was found for a higher percentage of EGFR detection in high-grade TCC. EGFR expression was significantly associated with tumor stage and patient survival (p0.01 and p0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Breast cancer diagnosis requires specific expertise from the Medical Doctors. Furthermore, prognosis, monitoring and early detection of malignant findings can be successfully realized through synergies between physicians, researchers and general population in concert with the health policy program of each country. Information technology and computational intelligence play a crucial role in the production of digital repositories and cancer registries as well as in the development of systems to support diagnosis. In this paper we present the concept and the architecture of an approved grant under the National Strategic Reference Framework 2007–2013 (NSRF), called e-Prolipsis. Through this project, we will design and implement a web based risk estimation platform and a Central Breast Cancer Registry (CBCR) that will co-operate to provide medical doctors and patients with services such as multiplicity in diagnostic opinions, synergy, computational risk estimation, access to statistical/epidemiological data for trend estimation. Such a system, will serve as a reference tool and will help the clinician, the radiologist, the rural doctor or trainee doctor in the final assessment on the existence or likelihood of breast cancer. The system will assist in the successful diagnosis of breast cancer, giving each patient access to a large pool of doctors and at the same time, the data stored in the CBCR will be used for statistical analysis, providing useful results for improving both the cancer detection application and for making a national policy for combating breast cancer. This system will be accessible through a Web Portal, with different access levels for patients, doctors and general public and different web services available to each user group, eliminating the geographical distances that would be imposed otherwise.

Motion of the carotid artery wall is important for the quantification of arterial elasticity and contractility and can be estimated with a number of techniques. In this paper, a framework for quantitative evaluation of motion analysis techniques from B-mode ultrasound images is introduced. Six synthetic sequences were produced using 1) a real image corrupted by Gaussian and speckle noise of 25 and 15 dB, and 2) the ultrasound simulation package Field II. In both cases, a mathematical model was used, which simulated the motion of the arterial wall layers and the surrounding tissue, in the radial and longitudinal directions. The performance of four techniques, namely optical flow (OF (HS)), weighted least-squares optical flow (OF (LK(WLS))), block matching (BM), and affine block motion model (ABMM), was investigated in the context of this framework. The average warping indices were lowest for OF (LK(WLS)) (1.75 pixels), slightly higher for ABMM (2.01 pixels), and highest for BM (6.57 pixels) and OF (HS) (11.57 pixels). Due to its superior performance, OF (LK(WLS)) was used to quantify motion of selected regions of the arterial wall in real ultrasound image sequences of the carotid artery. Preliminary results indicate that OF (LK(WLS)) is promising, because it efficiently quantified radial, longitudinal, and shear strains in healthy adults and diseased subjects.

The influence of various prostatic manipulations, including digital rectal examination, cystoscopy, transrectal ultrasonography and transrectal needle biopsy, on the serum prostatic-specific antigen (PSA) levels in 170 men, were examined. We found that digital rectal examination, cystoscopy and transrectal ultrasonography had no significant effect on PSA levels, except for transrectal needle biopsy, which caused an immediate increase of serum PSA in 96.2% of the patients lasting more than 2 weeks in 42.3% of the cases. In conclusion, serum PSA determination after digital rectal examination, after cystoscopy and after transrectal ultrasonography is accurate and reliable. On the other hand, we must wait about 6 weeks after needle biopsy before measuring PSA in the serum of patients with prostatic diseases.

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease, affecting approximately one million adults worldwide. This paper describes a young female patient who presented to the acute medical team with generalised tonic-clonic seizures and right hemiplegia on a background of MS. Radiological imaging revealed a large ring enhancing lesion exerting mass effect. We describe an unusual form of MS and discuss diagnostic pitfalls of tumefactive demyelinating lesions which can be mistaken for brain tumours and abscesses.

Background: Several skeletal muscle abnormalities have been identified in patients with chronic heart failure (CHF), including endothelial dysfunction. We hypothesized that skeletal muscle microcirculation, assessed by near-infrared spectroscopy (NIRS), is impaired in CHF patients and is associated with disease severity. Methods: Eighty-three stable patients with mildmoderate CHF (72 males, mean age 54 ± 14 years, body mass index 26.7 ± 3.4 kg/m 2) and 8 healthy subjects, matched for age, gender and body mass index, underwent NIRS with the vascular occlusion technique and cardiopulmonary exercise testing (CPET) evaluation on the same day. Tissue oxygen saturation (StO 2, %), defined as the percentage of hemoglobin saturation in the microvasculature compartments, was measured in the thenar muscle by NIRS before, during and after 3-minute occlusion of the brachial artery. Measurements included StO 2, oxygen consumption rate (OCR, %/min) and reperfusion rate (RR, %/min). All subjects underwent a symptom-limited CPET on a cycle ergometer. Measurements included VO 2 at peak exercise (VO 2peak, ml/kg/min) and anaerobic threshold (VO 2AT, ml/kg/min), VE/VCO 2 slope, chronotropic reserve (CR, %) and heart rate recovery (HRR 1, bpm). Results: CHF patients had significantly lower StO 2 (75 ± 8.2 vs 80.3 ± 6, p < 0.05), lower OCR (32.3 ± 10.4 vs 37.7 ± 5.5, p < 0.05) and lower RR (10 ± 2.8 vs 15.7 ± 6.3, p < 0.05) compared with healthy controls. CHF patients with RR

We report on a 63-year-old woman, previously in good health, who had undergone nephrectomy for clear cell renal cell carcinoma in 2002. Because of systemic relapse with multiple lung metastases in 2006, the patient was treated with sunitinib 50 mg daily on a 4-weeks on-/2-weeks off-schedule. After 3 years of treatment, she developed a purpuric rash on her feet and trunk. Biopsy revealed leukocytoclastic vasculitis. No other organ involvement was diagnosed. She was started on oral prednisone 30 mg daily with rapid resolution of the vasculitic skin lesions. Sunitinib was temporally discontinued and reintroduced at the same dose level. Reappearance of a less serious vasculitis after 2 cycles of re-treatment was resolved in the weeks off-treatment and by reducing the dose of sunitinib along with 5 mg of prednisone daily. One year after the diagnosis, the patient is still on this therapy. Oncology providers should be aware of this rare but potentially serious, possible adverse effect of sunitinib. Copyright © 2011 S. Karger AG, Basel.

Lower respiratory tract infections and tuberculosis represent some of the top health priorities in Europe. In the present report, the most recent advances in the field of disease control, clinical research and basic science of lower respiratory tract infections and tuberculosis are presented through analysis of some of the best abstracts presented at the 19th European Respiratory Society Congress in Vienna (Austria). Pathogenesis, diagnosis, treatment, prognostic factors and novel diagnostic techniques relevant for bacterial and viral infections, as well as new tools for the diagnosis of latent and active tuberculosis in different sub-groups of patients, are discussed. The growing epidemiological threat represented by multidrug-resistant and extensively drug-resistant tuberculosis cases is presented and its impact analysed. Copyright©ERS 2010.

Aims: Loss of phosphatase and tensin homologue (PTEN) leads to activation of several kinases, including mammalian target of rapamycin (mTOR), which promotes cell cycle progression. The aim was to study the expression of PTEN and phosphorylated (p)-mTOR in familial and sporadic invasive breast carcinomas and their relation to clinicopathological features, molecular indices (Wnt1) and patients' survival. Methods and results: PTEN and p-mTOR were detected immunohistochemically in 215 sections of invasive breast carcinomas (112 with a familial history of breast cancer). Image analysis was used and univariate and multivariate analyses employed for statistical evaluation of results. PTEN was detecte5d in the nucleus (73.5%) and p-mTOR in the cytoplasm (44.2%) of cancer cells. Loss of PTEN protein was more frequently detected in women with a familial history of breast cancer (72%) (P < 0.0001), while its expression was negatively correlated with Wnt1, in total (P = 0.049). p-mTOR showed a positive association with lymph node status (P = 0.010) and was found to have a negative impact on patients' overall survival (P = 0.016). Conclusions: Loss of PTEN protein expression appears to occur more frequently in women with a family history of breast cancer, whereas activation of mTOR protein seems to be related to a more aggressive phenotype. © 2010 Blackwell Publishing Limited.

Twenty-eight cases of prostatic adenocarcinomas have been selected and the mean argyrophil nucleolar organizer region (AgNOR) count for each case was evaluated. Nine of these tumors were of high, 13 of median and 6 of low differentiation. It was found that as the tumors became less differentiated, the AgNOR count increased (p less than 0.001). Stage of the disease, serum prostate-specific antigen (PSA) value, and DNA ploidy of all these cases have been examined as well but no statistically significant correlation among these three parameters and the AgNOR count was found.

Specimens from 30 cases of benign prostatichyperplasia and 75 cases of prostatic carcinomaobtained during suprapubic prostatectomy, transurethalresection of the prostate and radical prostatectomy,were stained immunohistochemically for S-100 protein,prostatic acid phosphatase (PAP), prostatic specificantigen (PSA), neuron specific enolase (NSE) andpolyclonal keratin. S-100 protein was positive in9.3% of prostatic carcinomas and negative in allcases of prostatic hyperplasia. PAP and PSA werepositive in all cases, while NSE was positive in 16%of the carcinoma cases. Polyclonal keratin waspositive in both cell layers of the double layeredhyperplastic prostatic epithelium with a more intensestaining pattern in the outer cell layer. The authorsbelieve that the S-100 protein immunoreactivityobserved in some prostatic carcinomas, reflecting thechange in the functional status of the neoplasticcells, might be of prognostic significance. They alsoemphasize the non-myoepithelial nature of the outercell layer of the double layered prostaticepithelium.

Olive mill waste water (OMWW) is a major environmental issue in the Mediterranean. We address this problem by investigating the wastes for the presence of biologically active compounds already detected in both olive oil and pomace. Two initial OMWW samples were filtered using two microporous filtering media: (a) clayey diatomite and (b) zeolitic volcanic tuffs, obtaining three filtered samples from each. All initial and filtrated samples were tested for their activity on platelet activating factor (PAF)-induced aggregation. The results showed that the initial samples contain biologically active compounds (PAF inhibitors) and that in their respective last-eluted filtered samples these compounds are purified. These eluted samples, along with their corresponding initial OMWW, were further separated with HPLC and the purified fractions responsible for the aforementioned biological activity, were further studied using chemical determinations and MS analysis. It was confirmed that the PAF inhibitor present in these fractions resembles the one isolated from olive oil. These results offer a new approach on the OMWW handling by offering an alternative use of this waste as starting material for nutritional and/or pharmaceutical purposes in the future.

In this paper a formal method is proposed, based on Attribute Grammars (AG), for rapid SoC prototyping. A generic platform is also proposed for the automatic SoC implementation of AG-based applications. The proposed system, given the specification of the application in the formalism of Attribute Grammars, automatically produces the necessary hardware modules for the syntactic and semantic analysis of input strings belonging to that grammar. The produced implementation tackles with the recognition task of the input string, using a hardware implementation of an extension of Earley's parallel parsing algorithm. Moreover, the system exhibits capabilities of inexactness. The attribute evaluation makes usage of a stack-based hardware. The hardware modules are described in Verilog Hardware Description Language (Verilog HDL) and synthesizedin a Xilinx Virtex-5 ML506 FPGA. For the illustration of the proposed system, an example from the area of hardware compilers is given.