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The main aim of this work was the maximization of the energy saving of balanced and unbalanced distribution power systems via system reconfiguration and the optimum capacitor’s bank choice, which were estimated by using a new algorithm: modified Tabu search and Harper sphere search (MTS-HSSA). The results demonstrated that the proposed method is appropriate for energy saving and improving performance compared with other methods reported in the literature for IEEE 33-bus adopted systems, including large scale systems such as IEEE 119 and the IEEE 123 unbalanced distribution system. Moreover, it can be used for unbalanced distribution systems distributed generators (DGs). The results demonstrated that the proposed method (the optimal choice of shunt capacitor (SC) banks and the optimal reconfiguration via the proposed algorithm) is appropriate for energy saving compared with different strategies for energy saving, which included distributed generation (DG) at different cost levels.

Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly utilized diagnostic and therapeutic modality for the treatment of obstructive extrahepatic biliary disease. In toddlers and infants ERCP is challenging and limited by the size of the common bile duct, reliance on fluoroscopy for bile duct cannulation, and indirect visualization of the bile duct via radiography. The SpyGlass™ cholangioscope (10 Fr, Boston Scientific) allows for direct visualization of bile duct pathology and enables targeted tissue biopsies within the bile duct. Case report: SpyGlass™ cholangioscopy was performed to diagnose, monitor, and therapeutically stent an embryonal rhabdomyosarcoma of the common bile duct in an 18-month-old girl who initially presented with jaundice. Initial ERCP brushings of the common bile duct proved non-diagnostic in this patient. Use of SpyGlass™ cholangioscopy allowed for visualization of the biliary mass and targeted biopsies, confirming embryonal rhabdomyosarcoma and defining the extent of disease in the right and left hepatic ducts. The child was treated with chemotherapy and radiation therapy with subsequent biopsies that have demonstrated no active disease. Conclusions: SpyGlass™ cholangioscopy is a valuable tool in the diagnosis and treatment of biliary obstructive lesions and can be utilized in children under the age of 2 with success. Keywords: Cholangioscopy, SpyGlass™, Pediatric

Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer. In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival. After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P

In complex geotechnical problems, to perform a realistic study related to the soil-structure interaction and bearing capacity of foundations, a centrifuge modeling must be considered. New centrifuge device for installation and testing screw pile models is designed and manufactured with different velocities depending on the value of N (gravity scaling factor) and applying compression, uplift and inclined loads during rotation and their electronic control. The new installation system for helical piles was used in this device to install each pile with different torque depending on its capacity. Helical piles represent one of the deep innovative foundations as an alternative for increasing the size of the existing foundation solutions. In this study, the helical pile models are tested by centrifuge device with different parameters embedded within sand with relative density (R.D) of 75% and 55% under compression load. These parameters are spacing ratio, diameter and number of helices. The installation torque causes a soil disturbance which increases by increasing the diameter of helix and R.D of soil. The reduction percentages of the bearing capacity of the helical pile models with two helices of diameter (40 mm) embedded in sand with R.D of 75% and 55% are 17% and 9%, respectively, and when R.D of (55%) and helix diameters of 40 mm and 50 mm are 9% and 15%, respectively.

One of the most important problems in Iraq is the insufficient and inefficiency of the electrical power generating station, that is causing many problems in the availability of electricity in public and private buildings. This problem is leading to use privet power generators, causing air pollution and highly energy consumption. The second exploratory symposium “the reality of power in Iraq and its impact on the society” which had been held on May 2011 in Iraq proposed a large number of recommendations, a standout amongst these proposals was: urge the utilization of the thermal insulation in the building’s roofs to reduce the energy consumption. This study will prompt to the new idea of “living cool” in the Iraqi houses and different types of buildings throughout the day without the electricity’s power using by utilizing the new thermal insulation technology. This study eventually examines the idea of the “COOL ROOF” innovation to Iraqi’s houses and public buildings. The problem of the energy consumption might be the critical issue over the world generally, what’s more done Iraq specially. The transmission of the energy through top roofs might be more than (50%) starting with those general transmission energies through the other surfaces. Roofs with “high solar reflection”, high daylight reflection and high thermal emittance “high heat radiant” are remaining unflappable throughout the day. Previous researches approved that “the roof surfaces with low thermal emittances properties and high solar reflection might also remain cool in the sun and throughout the day. Use this type of roofs (cool roof) will reduce cooling electricity power in the different types of buildings in Iraq. Cool roofs can also reduce the citywide encompassing air temperature over summer by decreasing those gigantic number for air-conditioning equipment, abating ozone framing furthermore, eventually expanding human comfort demands by using the nature and minimum requirements to reach human comfortable zones. This research has been used practical details to apply the cool roof technology in Iraq.

Soft, saturated, fine grained subgrade soils are distinguished by their low undrianed shear strength and high compressibility. Such soils cover most of the middle and southern parts of Iraq. The effect of using stone column, encased in geogrid and steel mesh to improve pavement's performance is experimentally investigated and evaluated. To compare the experimental and analytical outputs, three dimensions finite element throughout elastic and elasto-plastic models using ABAQUS ver.6.12.3 software are developed to simulate and analyze the relations between the cycling load and deformation of the suggested pavement modes. Based on the results and the limitation of this study it is concluded that, using encased stone columns, is more practical and suitable alternative to improve weak subgrade against permanent deformation as compared with the other simulated pavement modes. The results of ABAQUS program are very close to results of laboratory tests.

One of the most important pillars of sustainable development in all sectors is governance and decision-making. The transport sector in Iraq suffers from inefficiency and efficiency in its performance and development of other sectors. It is considered the biggest source of environmental pollution and the deterioration of the local and regional climate of Iraq because of traditional transport and traffic plans. The need for role of governance and decision-making in the Iraqi transport sector and make it sustainable need to develop an institutional framework through which the roles of different institutions and stakeholders in terms of financial management and decision-making, as well as adoption of the labor market approach that encourages the work of the private sector. The research concluded that governance and decision-making should be activated in all sectors; the transport sector is part of the overall system. The research recommended that the proposed framework be adopted as the starting point for a sustainable transport system to be applied in all Iraqi cities.

Background Candida is a ubiquitous organism in nature which inhabits the oral cavity as part of the normal microbial flora. The oral carriage of Candida is perpetuated by several predisposing factors. Methods This cross-sectional study was designed to investigate the carriage rate of Candida among 104 voluntary adults at the college of medicine - Jouf University. The concentrated oral rinse technique using Sabouraud Dextrose agar medium supplemented with 0.05% Chloramphenicol was used to isolate Candida. The relative factors affecting the colonization of Candida and the concentration of each type were also determined. Results Candida species were isolated from the oral cavity of 45 (43.4%) subjects. Of these 55.6% were identifies as C. albicans as determined by the Vitek 2 compact system. Other Candida species were represented by C. glabrata (11.1%), C. krusei (11.1%), C. dubliniensis (8.9%), C. parapsilosis (6.7%), C. tropicalis (4.4%), and C. famata (2.2%). Subjects with very poor plaque status, severe gingivitis and diabetes had significantly (P = 0.001) high concentration of Candida spp. Conclusion Plague, severe gingivitis, and diabetes were found to be significantly associated with higher Candida colonization.

Introduction & Objectives: PREVAIL was a phase 3 trial of enzalutamide vs placebo in asymptomatic or mildly symptomatic chemotherapy-naïve men with mCRPC. Overall survival (OS)was first evaluated after 784 (45.7%)deaths and median follow-up of 31 months. Here we report OS and safety after an additional 3 years of follow-up. Materials & Methods: Men with chemotherapy-naïve mCRPC were randomized 1:1 to enzalutamide 160 mg/day or placebo. OS and radiographic progression-free survival were coprimary endpoints in PREVAIL, which was halted after a preplanned interim analysis revealed superiority with enzalutamide. Eligible placebo patients could crossover to enzalutamide (n=234)in an open-label extension; these patients were included in the placebo group for the final analysis of OS. Results: 1717 men were randomized (1715 treated)to PREVAIL between September 2010 and September 2012. At the 5-year OS analysis reported here (data cutoff 30 September 2017; 5 years after the last patient was randomized)there were 1382 deaths (689 in the enzalutamide arm and 693 in the placebo arm). Survival probabilities at 2, 3, and 5 years favored enzalutamide (Table). Enzalutamide reduced the risk of death by 17% (HR, 0.83; 95% CI, 0.75-0.93; P=0.0008). Median OS was 35.5 months (95% CI, 33.5-38.0)in the enzalutamide arm vs 31.4 months (95% CI, 28.9-33.8)in the placebo arm, with a median follow-up time of 69 months. The treatment effect was consistent across all baseline disease specific subgroups. At the data cutoff, 70% of patients in the enzalutamide arm and 80% in the placebo arm had received ≥1 postbaseline antineoplastic therapy. The most common subsequent therapy was docetaxel (55% in the enzalutamide arm and 62% in the placebo arm), followed by abiraterone acetate (42% and 51%, respectively). Treatment-emergent adverse event (TEAE)was reported as the primary reason for discontinuation in 9.1% of patients in the enzalutamide arm and 6.0% in the placebo arm; 6.9% and 3.8% of patients had a TEAE that led to death. The most common (≥20%)AEs were fatigue (38.2% vs 26.1%), back pain (32.5% vs 22.4%), constipation (25.6% vs 17.4%), nausea (24.5% vs 22.7%), arthralgia (23.5% vs 16.2%), and decreased appetite (21.0% vs 16.6%)in the enzalutamide vs placebo arms, respectively. [Table Presented][Table Presented]Conclusions: With >5 years of follow-up, enzalutamide continued to demonstrate benefit vs placebo in OS in men with asymptomatic or mildly symptomatic mCRPC despite crossover in the placebo arm and multiple subsequent therapies. The safety profile was consistent with that reported previously.

Contains fulltext : 137932.pdf (Publisher’s version ) (Open Access) BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. RESULTS: The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients, particularly those with neutropenia and those undergoing bone marrow or stem cell transplants. Micafungin is an echinocandin antifungal drug with activity against all major Candida spp. Currently, micafungin is indicated for treatment of invasive candidiasis, oesophageal candidiasis and prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation or patients who are expected to have neutropenia. Micafungin demonstrates in vitro and in vivo activity against Aspergillus spp. It is currently not licensed to treat Aspergillus infections in the UK or USA. This review summarises the current evidence base surrounding the clinical use of micafungin in the treatment of invasive aspergillosis to consider the potential role of micafungin in these patients. There are currently no randomised studies comparing micafungin with standard antifungal therapy. Prospective non-randomised clinical studies, predominantly performed in Japan, involving 492 patients with aspergillosis and 455 febrile patients with chemotherapy-induced neutropenia suggest that micafungin may be as effective as comparator antifungal agents. Other clinical evidence is limited to case reports. Further experience in the form of randomised controlled trials is required to establish the exact role of micafungin in the context of currently available broad-spectrum antifungal agents.

Aim: This study aims to identify the prevalence of the use of rubber dam (RD) for isolation during resin composite restorations in a clinical scenario. It also aims to evaluate restorations done with and without RD for radiolucencies present postoperatively. Methods: A total of 50 voluntarily participating dentists were asked to do posterior composite restorations for primary caries lesions affecting the occluso-proximal surfaces. The isolation protocols followed were noted, and postoperative bitewing radiographs were evaluated independently by two investigators. The presence of radiolucencies between the tooth-restorative interface and in the body of the restoration was assessed and statistically evaluated using Chi-square test at a significance level of P≤ 0.05. Results: The results showed that 71.5% of the restorations were not done under RD isolation. There was a statistically significant difference in the number of radiolucent areas seen in restorations done with and without RD. Conclusion: This study shows a low percentage of clinicians use RD for isolation during composite restorations. It also indicates that radiolucent areas are more often associated with restorations done without RD isolation. This study stresses that there is a need to change the clinician's convictions about isolation protocols followed during composite restorations.

Renewable energy systems have become common in power systems. Many problems associated with connecting a renewable energy system to utility network have arisen. In the traditional power calculation, the resistance of the line is ignored because of large the X/R ratio. However, the R/X ratio in the distribution network is greater than in transmission. Because of that, the line resistance should be considered in the power calculations. In this paper, the effect of the grid resistance on transfer of power is investigated by calculating the active power between a PV system and the grid where the grid resistance is included. Two models were developed to study the effects of the grid resistance. The sensitivity of real and reactive power to the grid impedance, the current performance and the phase angle for the maximum power were studied under variations of the grid resistance. The results from both models have been compared to emphasize that the transfer of power is really influenced by the resistance of the line impedance.

A pavement structure consists of several layers for the primary purpose of transmitting and distributing traffic loads to the subgrade. Rutting is one form of pavement distresses that may influence the performance of road pavements. Soft subgrade soils are distinguished by their low undrianed shear strength and high compressibility. The effect of geogrid and steel mesh to improve the performance pavement is experimentally investigated and evaluated. To compare the experimental and analytical outputs, three dimensions finite element throughout models using ABAQUS ver.6.12.3 software are developed to simulate and analyze the relations between the cycling load and deformation of the suggested pavement modes. Based on the results and the limitation of this study it is concluded that, using geogrid and steel mesh in pavement layers leads to increases in load carrying capacity and decrease the permanent deformation in surface pavement for (1000) cycles load by (27.3%) and (18.3%) respectively, as compared with unreinforced model. The results of ABAQUS program are very close to results of laboratory tests.

In this study, an Erbium Doped Fiber Amplifier (EDFAs) simulation program has been written in Matlab to characterize Noise Figure variations of a forward pumped EDFAs operating in C band (1525-1565 nm) as functions of Er3+ fiber length, injected pump power, signal input power and Er3+ doping density. The effect of multiple amplified stage on the noise figure was student at different Fiber length and pumping power. The numerical results shows that EDFAs could be operated in saturation regimes leading minimum noise figure when the EDFAs is supplied with sufficient pump power, Moreover a continuous increasing of the noise figure value was demonstrated by increasing all of amplified stage number and fiber length.

While pancreatitis is uncommon in children, pseudocyst development can be a serious complication. Endoscopic drainage of pseudocysts is well established in adults. However, there are limited data regarding this procedure in a pediatric population. The objective of this study is to determine the safety and efficacy of endoscopic ultrasound-guided pseudocyst drainage in children. The study group included children (age

In this work, static and dynamical chracteristics of SCR(BT51) thyrister have been studied.In relate to static chracteristics, I-V relationship of this device has been illustrated at different temperatures as well as determination of threshold voltage values (Vth) ,studing it's variation as a function of temperature and the result obtaining from this study that the (Vth) is nonlinearly increasing with temperature increasing, this gives the fact that the device senstive to temperature variation.Also, the relationship between both of the conductance and the parameter with anode-cathode voltage variation have been explained.

Contains fulltext : 153233.pdf (Publisher’s version ) (Closed access) BACKGROUND: Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies. METHODS: In this placebo-controlled, double-blind, randomised phase 3 study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive prostate cancer stratified by Eastern Cooperative Oncology performance status (0 vs 1) were randomly assigned with a permuted block allocation scheme via a web response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (placebo group). Coprimary endpoints were radiographic progression-free survival and overall survival analysed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00887198. FINDINGS: At a median follow-up of 49.2 months (IQR 47.0-51.8), 741 (96%) of the prespecified 773 death events for the final analysis had been observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the placebo group. 238 (44%) patients initially receiving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo group received subsequent treatment with one or more approved agents. Median overall survival was significantly longer in the abiraterone acetate group than in the placebo group (34.7 months [95% CI 32.7-36.8] vs 30.3 months [28.7-33.3]; hazard ratio 0.81 [95% CI 0.70-0.93]; p=0.0033). The most common grade 3-4 adverse events of special interest were cardiac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the placebo group), increased alanine aminotransferase (32 [6%] vs four [

Item does not contain fulltext BACKGROUND: Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. METHODS: In this phase 3, double-blind, placebo-controlled trial, we recruited patients with progressive metastatic castration-resistant prostate cancer and no previous chemotherapy from 324 study centres (ie, hospitals or large urologic or group outpatient offices) in 43 countries. Eligible patients were randomly assigned in a 1:1 ratio to receive either 400 mg orteronel plus 5 mg prednisone twice daily or placebo plus 5 mg prednisone twice daily. Randomisation was done centrally with an interactive voice response system and patients were stratified by region (Europe, North America, and not Europe or North America) and the presence or absence of radiographic disease progression at baseline. The two primary endpoints were radiographic progression-free survival and overall survival, determined in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01193244. FINDINGS: From Oct 31, 2010, to June 29, 2012, 2353 patients were assessed for eligibility. Of those, 1560 were randomly assigned to receive either orteronel plus prednisone (n=781) or placebo plus prednisone (n=779). The clinical cutoff date for the final analysis was Jan 15, 2014 (with 611 deaths). Median follow-up for radiographic progression-free survival was 8.4 months (IQR 3.7-16.6). Median radiographic progression-free survival was 13.8 months (95% CI 13.1-14.9) with orteronel plus prednisone and 8.7 months (8.3-10.9) with placebo plus prednisone (hazard ratio [HR] 0.71, 95% CI 0.63-0.80; p

Objective: Flow probes have been introduced as a non-invasive means of anastomotic quality assessment in off-pump coronary artery bypass graft (CABG). Flow waveform morphology cannot reliably be assessed visually unless severe anastomotic stenosis is present ( . 90%). We applied spectral analysis techniques to determine whether the frequency content of graft flow can improve the surgeon’s ability to detect anastomotic errors. Methods: Forty-six mammary to left anterior descending artery (LAD) anastomoses were created in mongrel dogs during off-pump CABG surgery. Graft flow was measured using transit-time flow probes with the LAD closed, and the mammary graft patent and with varying degrees of stenosis. The degree of anastomotic stenosis was created by an artificial stitch and verified by random postoperative angiography. Spectral analysis of the graft flow waveforms was performed. Differences in the magnitude and phase components of the graft flow for the first five harmonics were determined for the varying anastomosis test conditions. Differences were determined using analysis of variance and least square means techniques. Results: The magnitude of the fundamental (zeroth) harmonic was statistically different in the internal mammary artery (IMA) with 0‐25% stenosis compared to IMA with 50‐75% stenosis (P , 0:01). Further, the magnitude of the first, second, and fourth harmonics were statistically different in IMA with 0‐25% compared to IMA with 75% (P , 0:01). The phase of the first harmonic was statistically different in IMA with 25% stenosis than IMA with 50% stenosis (P , 0:01). No differences in interaction between the LAD and IMA for all ranges of stenosis were detected (P . 0:50). Conclusion: Spectral analysis of graft flow waveforms may be beneficial in detecting lesser degrees of anastomotic stenosis (i.e. , 90%) compared to traditional visual assessment of mean graft flow and/or graft flow waveform morphology. q 1999 Elsevier Science B.V. All rights reserved.

Objective: Flow probes are being used for intraoperative assessment of anastomotic quality during off-pump coronary artery bypass grafting (CABG). We conducted a survey with the cooperation of 19 international surgeons to assess the ability of surgeons to detect anastomotic errors by evaluating mean flow and flow waveform morphology. Material and methods: Mongrel dogs underwent mammary to left anterior descending (LAD) grafting. Mean graft flow and flow wave morphology for varying degrees of anastomotic stenoses were recorded using transit-time flow probes. A questionnaire consisting of ten different recorded flow tracings and the corresponding mean flows were given to 20 surgeons from around the world. The surgeons were asked to determine the degree of stenosis and whether they would re-do the anastomosis based upon the mean flow and the flow tracings. Results: All of the 19 surgeons that responded were able to clearly identify a highly stenotic graft ( .90% stenosis). However, 24% would re-do a fully patent anastomosis, 58% accepted an anastomosis with moderate stenosis, and 72% accepted anastomoses with severe stenosis. Conclusions: Evaluation of flow tracing morphology and/or mean flows can be used to reliably detect nearly occluded anastomoses ( .90% stenosis). However, surgeons should be cautious in assessing anastomoses with lesser degrees of stenosis, as they may be more difficult to reliably interpret. © 1998 Elsevier Science B.V. All rights reserved

This paper proposes a novel Tuned Magnetic Fluid Damper (TMFD) with energy harvesting capabilities to concurrently mitigate structural vibrations and harvest vibratory energy. The energy harvesting TMFD consists of a rectangular container carrying a magnetized ferrofluid and mounted on a vibrating structure. The ferrofluids geometric and material properties (height, surface area, magnetization) are tuned such the first modal frequency of the fluid column matches the first modal frequency of the structure. The one-to-one resonant interactions between the structure and the fluid column results in a direct energy transfer mechanism which mitigates the vibration of the structure by channeling energy to the ferrofluid. Consequently, the fluid undergoes a sloshing motion with large-amplitude surface waves that change the orientational order of the magnetic dipoles in the fluid. This creates a time-varying magnetic flux, which induces an electromotive force in a coil wound around the container. The electromotive force transforms a small part of the fluids kinetic energy into electricity by generating a current in the coil. Experimental studies performed on an actual TMFD prototype clearly demonstrate its vibration suppression potential and energy generation capabilities.

Cancer is a genetic disease driven by both heritable and somatic alterations in DNA, which underpin not only oncogenesis but also progression and eventual metastasis. The major impetus for elucidating the nature and function of somatic mutations in cancer genomes is the potential for the development of effective targeted anticancer therapies. Over the last decade, high-throughput technologies have allowed us unprecedented access to a host of cancer genomes, leading to an influx of new information about their pathobiology. The challenge now is to integrate such emerging information into clinical practice to achieve tangible benefits for cancer patients. This review examines the roles array-based comparative genomic hybridization and next-generation sequencing are playing in furthering our understanding of both hematological and solid-organ tumors. Furthermore, the authors discuss the current challenges in translating the role of these technologies from bench to bedside.

Primary testicular non-Hodgkin lymphoma (PTL) comprises around 9% of testicular cancers and 1-2% of all non-Hodgkin lymphomas. Its incidence is increasing and it primarily affects older men, with a median age at presentation of around 67 years. By far the most common histological subtype is diffuse large B-cell lymphoma, accounting for 80-90% of PTLs. Most patients present with a unilateral testicular mass or swelling. Up to 90% of patients have stage I or II disease at diagnosis (60 and 30%, respectively) and bilateral testicular involvement is seen in around 35% of patients. PTL demonstrates a continuous pattern of relapse and propensity for extra-nodal sites such as the central nervous system and contralateral testis. Retrospective data have emphasised the importance of prophylactic radiotherapy in reducing recurrence rates within the contralateral testis. Recent outcome data from the prospective IELSG-10 trial have shown far better progression-free and overall survival than historical outcomes. This supports the use of orchidectomy followed by Rituximab- cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), central nervous system prophylaxis and prophylactic radiotherapy to the contralateral testis with or without nodal radiotherapy in patients with limited disease. Central nervous system relapse remains a significant issue and future research should focus on identifying the best strategy to reduce its occurrence. Here we discuss the evidence supporting combination chemotherapy and radiotherapy in PTL.

To the Editor: Diarrhea predominate irritable bowel syndrome (IBS-D) currently constitutes the largest sub-category of IBS causing a significant emotional and economic impact [1]. This entity has b...

In the past decade, there have been numerous studies which showed the feasibility of harvesting electrical energy from vibrating structures. The main goal of this study is first to generate a Finite Element (FE) model using ANSYS to verify an existing harvesting model. This FEM model can be used as a base for designing more complex harvesters. The second goal of this study is to optimize the parameters of a simple cantilever harvester to maximize the power generation from ambient mechanical energy. A distributed parameter model and its modal solution are used to identify the design variables through a parametric study. The results obtained using the distributed parametric model is compared with the results obtained using ANSYS. It is of interest to ensure adequate power generation under non-resonant conditions for a broad band excitation. The average power within a certain frequency range is used as the cost function to define optimization problem along with some geometric and physical constraints. We found that, in certain frequency ranges, the parameters can be optimized to generate maximum power. Having validated the methodology, work is in progress to design and optimize harvesters with complex geometries.Copyright © 2011 by ASME

Introduction Iron-deficiency anemia is a relatively common presenting feature of several gastrointestinal malignancies. However, cholangiocarcinoma has rarely been reported as an underlying cause. The association of cholangiocarcinoma with the rare clinical finding of hemobilia is also highly unusual. To our knowledge, this is the first case report of cholangiocarcinoma presenting with acute hemobilia and chronic iron-deficiency anemia. Case presentation We report the case of a Caucasian, 84-year-old woman presenting with recurrent, severe iron-deficiency anemia who was eventually diagnosed with intra-hepatic cholangiocarcinoma, following an acute episode of hemobilia. A right hepatectomy was subsequently performed with curative intent, and our patient has now fully recovered. Conclusion This is a rare example of hemobilia and chronic iron-deficiency anemia in association with cholangiocarcinoma. We suggest that a diagnosis of cholangiocarcinoma should be considered in patients who present with iron-deficiency anemia of unknown cause, particularly in the presence of abnormal liver function.

Diarrhea Predominant Irritable Bowel Syndrome IBS (IBS-D) and functional diarrhea constitute 50% of cases treated by gastroenterology specialists and a significant proportion of those treated in a primary physicians practice. The size of the problem and the difficulty in successfully addressing these entities has frustrated patients and physicians alike. The presented data delineates work-up, final diagnoses and clinical outcomes in the largest single clinical retrospective study of 303 patients with an initial presentation of IBS-D and functional diarrhea. Results indicate that 298 (98%) patients were found to have a diagnosis different from the initial presentation of IBS-D, and 204 (68%) of the patients studied had conditions related to treatable bile acid abnormalities. After identifying these clinical diagnoses and instituting appropriate therapy, 98% of these patients had a favorable response, as measured by a decrease in the number of bowel movements to less than three per day and a significant change in the consistency of the stools. This finding is dramatically different from the poor response generally experienced from conventional therapy for IBS-D and functional chronic diarrhea. The data presented in this study substantiates the hypothesis that IBS-D and functional diarrhea do not exist as true clinical entities and explains the previous lack of satisfactory therapeutic response. Symptoms experienced by these patients were caused by a collection of different clinical conditions bunched up under this "umbrella" diagnosis of IBS-D. Once these separate entities were identified and appropriately addressed, the clinical response was quite impressive and encouraging. The implication of this hypothesis could be of vital importance because of the number of those suffering from these symptoms.

Previous studies have identified abnormalities in the oxidative responses of the neutrophil in cystic fibrosis (CF), but it is unclear whether such changes relate to loss of membrane cystic fibrosis transmembrane conductance regulator (CFTR) or to the inflammatory environment present in this disease. The aim of the present study was to determine whether neutrophils from CF patients demonstrate an intrinsic abnormality of the respiratory burst. The respiratory burst activity of neutrophils isolated from stable DeltaF508 homozygote CF patients and matched healthy controls was quantified by both chemiluminscence and cytochrome C reduction. Expression of NADPH oxidase components and CFTR was determined by Western blotting and RT-PCR. The oxidative output from neutrophils from CF in response to receptor-linked and particulate stimuli did not differ from that of controls. Expression of NADPH oxidase components was identical in CF and non-CF neutrophils. While low levels of CFTR mRNA could be identified in the normal human neutrophil, we were unable to detect CFTR protein in human neutrophil lysates or immunoprecipitates. CFTR has no role in controlling neutrophil oxidative activity; previously reported differences in neutrophil function between CF and non-CF subjects most likely relate to the inflammatory milieu from which the cells were isolated.

The anti-inflammatory potential of macrolides was first appreciated with the successful use of erythromycin in the treatment of diffuse panbronchiolitis, a disease principally affecting the Japanese, and characterised by a persistent neutrophilic inflammatory infiltrate of the bronchi. While there are only limited data on the efficacy of other macrolides in treating this condition,1 the observation has generated considerable interest in examining the role of macrolides in other respiratory diseases where chronic airways inflammation is a prominent feature. Azithromycin (AZM) is a 15-membered macrolactam ring macrolide which, in randomised controlled studies, has demonstrated a beneficial role in the treatment of cystic fibrosis (CF)2–5 despite its lack of direct bactericidal or bacteriostatic activity against Pseudomonas aeruginosa . More recent (albeit smaller) studies have suggested a role for AZM in the treatment of bronchiolitis obliterans syndrome (BOS)6 and asthma,7 with a common finding in both being its ability to reduce airway neutrophilia. Such observations have focused attention on understanding how AZM and other macrolides may modulate host-pathogen interactions in chronic lung infection and their role as an immunomodulatory agent in both respiratory and non-respiratory settings. Clinical studies have usually been designed to study an individual macrolide agent, but it is likely that the findings in such trials represent a “class effect”. Although some in vitro experiments have suggested subtle differences between individual class members, the in vivo significance of these observations is uncertain. The direct antimicrobial activity of macrolides against Gram-positive bacteria results from inhibition of bacterial protein synthesis. Although AZM has little direct activity against Gram-negative organisms, it has been shown to modulate bacterial virulence factors and thus affect the outcome of chronic infections with organisms such as P aeruginosa . Quorum sensing is a sophisticated mechanism whereby pathogen-derived molecules act as auto-inducers and trigger a …

Background & Aims Acute pancreatitis is rare during pregnancy; limited data are available about maternal and fetal outcomes. We investigated the effects of acute pancreatitis during pregnancy on fetal outcome. Methods This retrospective cohort study, performed at a single academic center, included consecutive pregnant women who presented with (n = 96) or developed acute pancreatitis in the hospital (n = 7) in 2000–2006 (mean age, 26 y). Patient histories and clinical data were collected from medical records. Results Of the 96 patients with spontaneous pancreatitis, 4 had complications: 1 patient in the first trimester had acute peripancreatic fluid collection, and 3 patients in the third trimester developed disseminated vascular coagulation (DIC). None of these patients achieved term pregnancy, and 1 of the patients with DIC died. Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 23 patients with acute pancreatitis; post-ERCP pancreatitis was diagnosed in 4 patients (a total of 11 patients developed ERCP-associated pancreatitis). Term pregnancy was achieved in 73 patients (80.2%). Patients who developed pancreatitis in the first trimester had the lowest percentage of term pregnancy (60%) and highest risks of fetal loss (20%) and preterm delivery (16%). Of the patients with pancreatitis in the second and third trimesters, only one had fetal loss. Fetal malformations were not observed. Conclusions The majority of pregnant patients with acute pancreatitis did not have complications; most adverse fetal outcomes (fetal loss and preterm delivery) occurred during the first trimester. Acute pancreatitis, complicated by DIC, occurred most frequently in the third trimester and was associated with poor fetal and maternal outcomes.

Diagnostic esophagogastroduodenoscopy (EGD) is generally a very safe procedure. We report the first case of iatrogenic esophageal submucosal dissection after an attempted diagnostic gastroscopy in a patient with a small previously undiagnosed Zenker's diverticulum (ZD). After EGD, she developed severe dysphagia with the inability to swallow solids, liquids, and even her own saliva. On barium swallow study, there was a column of contrast below the upper esophageal sphincter, and this was misdiagnosed as a large ZD by the radiologist. The resultant stricture was successfully managed with endoscopic balloon dilatation under fluoroscopy with wire-guided cannulation. The ZD was treated with flexible endoscopic clip-assisted diverticulotomy. Iatrogenic submucosal dissection is a unique complication of upper endoscopy. Endoscopists, otolaryngologists, radiologists, and cardiothoracic surgeons should be aware of this condition and prepare to manage it appropriately. If the patient is stable and the possibility of perforation is small, conservative and supportive care can be tried first. A surgical gastrostomy tube can be placed for enteral feeding. In patients with ZD, ZD recognition and gentle manipulation is strongly recommended during esophageal intubation.

Background: In treating Zenker's diverticulum (ZD), there are potential risks associated with performing flexible endoscopic diverticulotomy without suturing or stapling. We recently introduced flexible endoscopic clip-assisted diverticulotomy (ECD) in treating ZD by securing the septum prior to dissection. Objective: To evaluate the feasibility and safety of ECD for complete septum dissection. Study Design: Case series at an academic center. Seven consecutive patients (mean age 71 y; range 48–91 y) with symptomatic ZD of various craniocaudal sizes based on radiographic measurements (mean 2.6 cm; range 0.8 cm–4.5 cm) were included. The mean depth of the septum was 1.73 cm (range 0.3 cm–3.1 cm). The mean duration of symptoms was 4.8 years (range 0.5–10 y). Methods: After endoclips were placed on either side of the cricopharyngeal bar, the septum was dissected between these two clips down to the inferior end of the diverticulum with a needle-knife. Procedures including “one-step ECD” (n = 1), “stepwise ECD” (n = 3), and “bottom ECD” (n = 2) were performed based on the septum depth of the ZD during endoscopy. ECD was not performed on one patient due to severe mucosal fragility of the esophageal inlet. Iatrogenic blunt dissection of the septum by the endoscopic hood occurred secondary to patient retching during the procedure. Main outcome measurements were symptom resolution and complications. Results: All patients (n = 6) who underwent ECD had complete resolution of esophageal symptoms at a minimum 6-month follow-up. There were no procedural complications. The patient who did not undergo ECD developed an esophageal perforation. She was managed conservatively without surgical intervention. On follow-up, her dysphagia was completely resolved. Conclusions: ECD is feasible, safe, and effective for complete septum dissection. ECD and endoscopic stapler-assisted diverticulotomy are complimentary rather than competing strategies in approaching ZD. Study limitations include the case series design and limited follow-up period.

Roux-en-Y gastric bypass (RYGBP) is the most commonly performed bariatric operation in the USA. We hypothesize that therapeutic endoscopy can be used to treat some unusual post-operative complications. We report two cases of early post-operative complications: (1) gastrogastrotomy (GG) stricture and (2) "trans-mesenteric tunnel" or "mesocolic" jejunal stricture. Endoscopic strictureplasty/revision of the gastric pouch of a bypass after gastroplasty was performed. The mesocolic stricture was managed with endoscopic dilatation using the achalasia dilating balloon under fluoroscopic and endoscopic guidance. With endotherapy, the patient with the GG stricture did not require re-operation, and there were no complications or stricture recurrence. The patient with mesocolic stricture responded short-term to endotherapy but ultimately required surgical adhesion lysis. None of these patients developed any procedure-related complications. Thus, in patients with unusual post-operative complications after RYGBP, endotherapy may be useful when there is good collaboration between the endoscopist and the surgeon.

Background During fluoroscopy, radiologists and gastroenterologists are able to manipulate live fluoroscopic video for better orientation and visualization. During endoscopy and natural orifice transluminal endoscopic surgery (NOTES), this function is not currently available. Particularly during NOTES, the endoscopic image is sometimes inverted, and off-axis operation is required. Objective Our purpose was to develop and test a prototype live video manipulator (LVM) for endoscopy, laparoscopy, and NOTES. Design Prospective ex vivo and in vivo feasibility study. Interventions We developed a prototype LVM software for video image manipulation that can be easily installed on any computer. The video input is streamed into the computer and can be displayed on a standard monitor. LVM was tested ex vivo in the following functions: (1) instant live video rotation, (2) vertical or horizontal video inversion, (3) mirror imaging, and (4) digital zooming. These functions were also tested during upper and lower GI endoscopy, ERCP, diagnostic laparoscopy, and various transvaginal NOTES procedures (cholecystectomy, gastroenterostomy, and sleeve gastrectomy) in porcine models. Main Outcome Measurements Image quality observation between unmanipulated and manipulated live videos. Results LVM reliably and easily performed live video manipulation during these tests. Besides standard definition video signals, LVM is fully compatible with high-definition video endoscopy. Three observers reported that the subjective image quality was the same in specified areas between manipulated and unmanipulated live videos. Limitations Observation and feasibility study. Conclusions LVM reliably and conveniently performed live video manipulations. LVM requires minimal equipment, capital investment, and maintenance, and is easy to set up. LVM can be a useful tool in many medical imaging studies, including endoscopy, laparoscopy, and NOTES, either as a built-in technology or as an as-needed add-on feature.

After orthotopic liver transplantation (OLT), allograft rejection remains an important problem and is the major reason that immunosuppressive therapy must be administered. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory mediator that is central to the immune response, and intragraft expression of this cytokine is increased during acute cellular rejection (ACR). Polymorphisms within the TNF promoter have been identified and correlated with alterations in production. The aims of this study were to determine if an individual patient's propensity to develop ACR is related to the presence of these genetic polymorphisms (either alone or in combination) within donor and recipient tissue and to determine if these polymorphisms affect patient survival after OLT. The study group consisted of 210 patients who underwent OLT between 1989 and 1999 with at least 6 months survival, including 42 cases who had evidence of acute cellular rejection (biopsy-proven, elevated enzymes, and response to increased immunosuppression) and were matched 4:1 to controls (n = 168) with similar age, gender, underlying liver disease, date of transplant, and baseline immunosuppression. The underlying liver diseases were hepatisis C virus (HCV)/alcohol (70), HCV alone (50), alcohol (30), primary biliary cirrhosis (15), primary sclerosing cholangitis (15), autoimmune hepatitis/cirrhosis (10), cryptogenic (15), and hepatitis B virus (HBV) (5). DNA was extracted from paraffin-embedded donor and recipient liver tissue (total 420 samples), amplified, and sequenced for TNF single-nucleotide polymorphisms (TNFA-308 A/G and TNFA-238 A/G). We found no differences between the TNF allelic distributions among donors without liver disease (presumably representative of a normal control population) and patients with end-stage liver disease undergoing OLT. Multivariate analysis revealed no association with TNF polymorphisms (within donor or recipient tissue) and rejection risk or patient survival after transplantation. In this large case control analysis of patients undergoing liver transplantation for diverse etiologies, TNF promoter polymorphisms were not independently associated with rejection or survival.

The study of hemodynamics associated with coronary atherosclerotic stenosis has been limited due to the lack of a safe, accurate, and reliable technique to create an artificial stenosis in an animal model. Existing techniques have often resulted in myocardial infarction (MI) or severe injury to the vessel and have been difficult to accurately quantify and reproduce. We developed a new technique to create an artificial stenosis in the native left anterior descending (LAD) coronary artery using a hemoclip in an experimental off-pump coronary artery bypass graft (CABG) animal model that overcomes these limitations. The native LAD was dissected at its proximal end and a hemoclip was applied to create varying degrees of artificial stenosis in 30 mongrel dogs during experimental off-pump CABG procedures. The precise application of the hemoclip was predetermined using a mathematical formula to calculate the reduced circumference required to create a specific stenosis. Using these calculations, artificial stenoses of 25%, 50%, 75%, and 90% were created in the LAD. Postoperative angiography demonstrated only 5-10% error between the true (angiography) and estimated (hemoclip technique) stenosis values. In all cases, the vessel remained intact without any apparent external trauma, and no indications of MI were present during electrocardiograph (ECG) monitoring. The creation of an artificial coronary stenosis using the hemoclip technique was safe, reliable, easy, and accurate.

Objective: The intra-operative assessment of the quality of anastomosis in minimally invasive coronary artery bypass surgery (CABG) is critical. Recent investigations demonstrated that flow probes used intra-operatively to assess anastomotic errors may give the surgeon a false sense of confidence as only severely stenotic anastomoses (.90%) could be reliably detected. We developed a neural network system using graft flow data and assessed its potential to improve anastomotic error detection. Methods: Mammary to LAD grafts (na 46) were constructed in mongrel dogs off-pump. Continuous beat-to-beat graft flow was recorded using transit-time flow probes. Various degrees of anastomotic stenoses (0‐100%) were created by an additional suture. The degree of anastomotic stenosis was confirmed by postoperative angiography. A learning vector quantization neural network was created using heart rate, mean aortic pressure, mean systolic, maximum systolic, minimum systolic, mean diastolic, maximum diastolic, minimum diastolic, and mean graft flows. In addition, a spectral analysis of the flow waveforms was performed and the magnitude and phase of the first five harmonics were used to further develop the neural network. Results: The neural network pattern recognition system was 94% accurate in detecting any stenosis .50%. To validate the model, a testing set was used with 20% of the data values, and the accuracy remained at 100% above chance alone. Conclusion: Pattern recognition of transittime flow probe tracings using neural network systems can detect anastomotic errors significantly better than the surgeon’s visual assessment, thereby improving the clinical outcome of minimally invasive CABG. q 1999 Elsevier Science B.V. All rights reserved.