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Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

The authors show that antiferromagnetism can be stabilized when a small amount of Fe is intercalated in the van der Waals gap of 1T-TaS${}_{2}$. When they compare the temperature-pressure phase diagram of Fe-intercalated 1T-TaS${}_{2}$ with that of pristine 1T-TaS${}_{2}$, they conclude that the antiferromagnetic region is close to, but decoupled from, the Mott insulating phase of pristine 1T-TaS${}_{2}$.

Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor’s efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162 ; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138 ; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571 )

Few-layer black phosphorus is a monatomic two-dimensional crystal with a direct band gap that has high carrier mobility for both holes and electrons. Similarly to other layered atomic crystals, like graphene or layered transition metal dichalcogenides, the transport behavior of few-layer black phosphorus is sensitive to surface impurities, adsorbates, and adatoms. Here we study the effect of Cu adatoms onto few-layer black phosphorus by characterizing few-layer black phosphorus field effect devices and by performing first-principles calculations. We find that the addition of Cu adatoms can be used to controllably n-dope few layer black phosphorus, thereby lowering the threshold voltage for n-type conduction without degrading the transport properties. We demonstrate a scalable 2D material-based complementary inverter which utilizes a boron nitride gate dielectric, a graphite gate, and a single bP crystal for both the p- and n-channels. The inverter operates at matched input and output voltages, exhibits a gain of 46, and does not require different contact metals or local electrostatic gating.

Background: The unsatisfactory side branch (SB) ostial strut coverage remains a problem in coronary bifurcation stenting. Both the surplus and lack of struts at SB ostium may be the causative mechanism. We propose that the inability of available stents to cover the “extension distance” of the bifurcation region is the cause of in-stent restenosis. Methods: The extension distance (ED) is defined as the maximal distance at the carina tip, which must be covered by the stent struts to ensure optimal coverage of the main branch (MB) and SB openings. A mathematical model was created, representing the key factors that govern geometrical reconfigurations after stent implantation in bifurcations. There are two options—with and without bifurcation region deformation. The theoretical assumptions were tested on a bifurcation model (soft polyvinylchloride polymer tubes) permitting free wall deformations and the following parameters: Parent Vessel, MB, SB diameters of 3.5, 3.0, and 2.5 mm, respectively, with an angle of 45° between the MB and SB. After stenting, final KBI with 3.5 mm and 3.0 mm balloons was performed up to 20 atm. Results: After the carina displacement, the ED, which has to be covered, is considerably smaller if the suboptimal result (DS >50%) at the SB ostium is acceptable. The maximal EDs from the bench test measurements are: Vision, Abbott Vascular – 5.62 mm ± 0.04; Liberte, Boston Scientific Corp. – 5.2 mm ± 0.03; Chopin2, Balton – 4.58 mm ± 0.05; Volo, Invatec – 4.41 mm ± 0.04; Driver, Medtronics – 4.39 mm ± 0.04; BxSonic, Cordis, J&J – 4.48 mm ± 0.05. The theoretical maximal ED of the model is 6.91 mm—28–62% larger than actually observed with different stents. Conclusions: The achievement of perfect ostial coverage of the SB is unsatisfactory with most of the currently available stents, especially when poststenting excessive dilation of the ostium of the SB is performed. (J Interven Cardiol 2010;23:305–318)

Overrepresentations in 20q have been reported in a number of ovarian cancers by comparative genomic hybridization. In order to study the relation of the increased copy number of 20q13.2 with tumor phenotype in ovarian cancer, we applied FISH on a tissue microarray. The TMA technology enables us to analyze a large number of different malignancy, histology, stage and grade tumors. Overall, the frequency of 20q13.2 alterations in epithelial ovarian cancer was 25.50% (10.74% gains and 14.76% amplifications). There was not statistically significant difference between the frequencies of 20q13.2 copy number changes in different grade tumors. The frequency of gains and amplifications increased significantly from stage I to stage II to stage III tumors. Our results showed strong association between increases 20q13.2 copies and advanced tumor stage. We concluded that genetic alterations in 20q13.2 may be of prognostic significance for stage progression of the ovarian cancer.

Guidelines and Expert Consensus Documents summarize and evaluate all available evidence with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on outcome and the risk benefit ratio of diagnostic or therapeutic means. Guidelines are no substitutes for textbooks and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s). The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/ guidelines/rules). Members of this Task Force were selected by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) to represent all physicians involved with the medical and surgical care of patients with coronary artery disease (CAD). A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk benefit ratio. Estimates of expected health outcomes for society are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2. The members of the Task Force have provided disclosure statements of all relationships that might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at European Heart House, headquarters of the ESC. Any changes in conflict of interest that arose during the writing period were notified to the ESC. The Task Force report received its entire financial support from the ESC and EACTS, without any involvement of the pharmaceutical, device, or surgical industry. ESC and EACTS Committees for Practice Guidelines are responsible for the endorsement process of these joint Guidelines. The finalized document has been approved by all the experts involved in the Task Force, and was submitted to outside specialists selected by both societies for review. The document is revised, and finally approved by ESC and EACTS and subsequently published simultaneously in the European Heart Journal and the European Journal of Cardio-Thoracic Surgery. After publication, dissemination of the Guidelines is of paramount importance. Pocket-sized versions and personal digital assistant-downloadable versions are useful at the point of care. Some surveys have shown that the intended users are sometimes unaware of the existence of guidelines, or simply do not translate them into practice. Thus, implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations.

Ultrathin black phosphorus is a two-dimensional semiconductor with a sizeable band gap. Its excellent electronic properties make it attractive for applications in transistor, logic and optoelectronic devices. However, it is also the first widely investigated two-dimensional material to undergo degradation upon exposure to ambient air. Therefore a passivation method is required to study the intrinsic material properties, understand how oxidation affects the physical properties and enable applications of phosphorene. Here we demonstrate that atomically thin graphene and hexagonal boron nitride can be used for passivation of ultrathin black phosphorus. We report that few-layer pristine black phosphorus channels passivated in an inert gas environment, without any prior exposure to air, exhibit greatly improved n-type charge transport resulting in symmetric electron and hole transconductance characteristics.

Black phosphorus exhibits a layered structure similar to graphene, allowing mechanical exfoliation of ultrathin single crystals. Here we demonstrate few-layer black phosphorus field effect devices on Si/SiO$_2$ and measure charge carrier mobility in a four-probe configuration as well as drain current modulation in a two-point configuration. We find room-temperature mobilities of up to 300 cm$^2$/Vs and drain current modulation of over 10$^3$. At low temperatures the on-off ratio exceeds 10$^5$ and the device exhibits both electron and hole conduction. Using atomic force microscopy we observe significant surface roughening of thin black phosphorus crystals over the course of 1 hour after exfoliation., Accepted to Applied Physics Letters, 12 pages, 3 figures

There is mounting evidence that the use of the radial access, without compromising procedural success, reduces bleeding complications compared to the femoral. Despite the proven efficacy, safety and benefits, the rate of penetration of radial access worldwide is still low – around 10% with a wide variation in adoption from over 50% in France, 40% in Japan to as little as 1% in the US (around 5% according to most recent data). The benefits that are inherent to the radial approach occur when radial approach is used in >70% of patients. Like any new technique, the radial approach has an inherent learning curve which may be shortened by a properly implemented radial programme and optimal access technique1. In the current issue of this journal there are three articles on the radial approach which are focused on: predictors of choice and success; the effect of different heparin regimens on patency; and new puncture techniques. In a subanalysis of the previously published PREVAIL study, Pristipino et al have tried to identify the predictors of the choice and success rates of radial artery catheterisation (RAC) in contemporary real world cardiology practice2. To date, this is the first study that has sought to identify these factors formally in a large cohort of unselected patients undergoing RAC by operators with different levels of expertise and across centres with varying volumes of activity. The first original finding is that in 90% of cases the choice of first arterial access site was determined by operator preference, while clinical or technical factors affected the choice in only a small minority. Patients undergoing RAC at hospitals with high overall procedural volumes exhibited a similar rate of RAC failure as those undergoing the procedure at low volume hospitals. However, assessing RAC volumes alone, patients undergoing the procedure at high volume hospitals experienced a statistically lower rate of RAC failure than their low-volume hospital counterparts. The failure rate for first radial access decreased almost tenfold, from 33% to 3.8%, when operators with 85% of their personal case load performed by RAC. Currently, radial access failure rate for high-volume operators performing over 90% of procedures radially is less than 1%3. The authors conclude that a routine RAC is superior to a selective strategy in terms of feasibility and success rate. For the first time, the study provides evidence that, contrary to general belief, the routine use of RAC in all-comers is feasible, safe and more successful than its selective use. In the second article, Ludvwig et al describe a new approach for RA puncture that represents a combination of the two most frequently techniques used nowadays, namely the bare needle technique and the venous cannula puncture technique4. The choice between the two cited techniques is mainly operator dependent, and none of the two has emerged as clearly better than the other5. The modified radial puncture technique combines the advantages of the bare needle and venous cannula techniques. The proposed approach is achieved in two steps: First, the radial puncture is accomplished with a bare needle without local anaesthesia, and according to the authors, patient discomfort is minimal and radial spasm virtually eliminated. In the second step, the combination of the retrieved needle introduced into a venous cannula is inserted over the introducer wire into the artery. The described modification of mainstream techniques does not make easier or shorter the access to the radial artery and it may be even slightly more timeconsuming. The main advantage, however, is not an easier puncture, but the ability to perform angiography and locally apply drugs, if needed, before a sheath is introduced. In the third article, the elegantly designed study by Schiano et al focuses – for the first time – on the potential influence of different heparin regimens on radial artery occlusion and bleeding

We examine the problem of two particles confined in an isotropic harmonic trap, which interact via a finite-ranged Gaussian-shaped potential in two spatial dimensions. We derive an approximative transcendental equation for the energy and study the resulting spectrum as a function of the interparticle interaction strength. Both the attractive and repulsive systems are analyzed. We study the impact of the potential's range on the ground-state energy. Complementary, we also explicitly verify by a variational treatment that in the zero-range limit the positive delta potential in two dimensions only reproduces the non-interacting results, if the Hilbert space in not truncated. Finally, we establish and discuss the connection between our finite-range treatment and regularized zero-range results from the literature., 19 pages, 5 figures, 1 table

The quantum many-body dynamics of indistinguishable, interacting particles are described by the time-dependent many-body Schrodinger equation (TDSE). The TDSE constitutes a difficult problem and is not solvable analytically in most cases. The present review article expedites and benchmarks the capabilities of a novel theoretical method, the multiconfigurational time-dependent Hartree method for bosons (MCTDHB) that is designed for solving the TDSE of interacting bosonic particles. The MCTDHB package is a software implementation that solves the equations of motion of MCTDHB numerically. It is assessed with a benchmark versus an analytically treatable model of trapped interacting bosons (a closed system) that the MCTDHB is capable of solving the TDSE for bosons numerically exactly, i.e., to any desired numerical precision. Furthermore, the structure and parallelization of the MCTDHB package as well as an application to the tunneling to open space dynamics [Proc. Natl. Acad. Sci. USA, 109, 13521 (2012)] are discussed.

Our purpose was to investigate the diagnostic value of the RNA-based HPV test (NucliSENS EasyQtm HPV) which utilizes NASBA technology for determination of the expression of E6/E7 of five high-risk HPV types (16, 18, 31, 33 u 45).Two hundred women aged 16 to 61 (mean 34.44) were prospectively studied. All of the women were subject to colposcopy, cytology and target biopsy. PCR DNA typing for 12 high-risk HPVs and RNA typing for E6/E7 oncogenes of five high-risk HPV were performed in parallel with a diagnostic kit NucliSens HPV v1.0 (bioMerieux).The colposcopy showed 119 normal and 81 abnormal findings (mild in 70 and heavy in 11). Cytological results were normal and non-neoplastic in 167, low-grade in 30 and high-grade in 3 women. The histological examination showed normal and inflammatory changes in 50, HPV findings in 94, low grade CIN in 35 and high grade CIN in 21 patients. DNA tests were positive in 148 (74.37%) women, 60 (40.54%) with one and the rest with 2 and more genotypes. A positive RNA-NASBA test with one genotype was found in 23 women. The comparison of the two typing tests established a full correlation between the detected by the PCR high-risk type HPV and the presence of E6/ E7 mRNA transcripts from the same HPV genotype.Our results confirmed the high diagnostic possibilities of NASBA technology. This gave women with precancerous lesions of the cervix an opportunity to receive more precise diagnostics.

Background: We selected 5 oncogenes with well-established roles in carcinogenesis – CCND1, ErbB1, ErbB2, c-mycand ZNF217– to investigate the coexistence of their copy imbalances in relation to the clinico-pathological characteristics of ovarian tumors. Materials and Methods: Fluorescence in situ hybridization for the 5 genes was applied to a preexisting tissue microarray. 38 ovarian tumors were successfully analyzed for copy number changes of the 5 genes. Results: At least one of these oncogenes was gained/amplified in 27 out of 38 tumors (71.1). We report the highest frequency of c-mycgenetic gain/amplification since it affected 42.1 of the ovarian tumors. We observed sequential involvement of copy number alterations of the other genes in the presence of c-mycdisruption. The incidence of copy number changes of the 5 oncogenes – both single and combinatorial – was higher in high-grade tumors. All double aberrations in the serous group comprised c-mycand ZNF217copy number increases. Conclusions: Our results revealed a combination between copy number increases of c-mycand ZNF217, associated with serous histology. The data from this combined analysis of the 5 oncogenes could be used as a basis in considering the combined approach in molecular-based therapy of ovarian cancer.

The overactive bladder syndrome (OAB) is a pathological condition that affects millions of people round the world. Its incidence increases with ageing. The main therapeutic option for OAB nowadays is anti-muscarinic drug therapy.To define and implement the diagnostic criteria, clinical guidelines in our country and to evaluate the results of Solifenacin therapy in patients with OAB.Along a three years period (2006-2009) 163 OAB patients were analyzed followed and treated. In our group of patients 106 (65.2%) are females and 57 (34.8%)--males. The diagnosis is based mainly on the complaints of the patient, evaluated thoroughly with a detail anamnesis and questionnaires. Urodynamic studies were performed In some of the patients. The efficacy of Solifenacin therapy has been validated with the same methods used in SUNRISE and VENUS studies.The mean age of female patients in our group is 63.8 years, and 65.6 years for males. The most commonly observed symptoms of OAB are urgency--88.3% and frequency--92%. Urge-incontinence is observed in 48.8% of the cases. Therapy with Solifenacin 5 and 10 mg has alleviated urgency in 82% and urge-incontinence in 88.9%. Mean number of pads used for 24 hours has decreased from 2.6 to 0.4 after therapy.Urgency is the main mandatory symptom for the diagnosis OAB. Therapy with Solifenacin 5 and 10 mg guarantees very good clinical results, and high degree of compliance of the patients.

The unsatisfactory side branch (SB) ostial strut coverage remains a problem in coronary bifurcation stenting. Both the surplus and lack of struts at SB ostium may be the causative mechanism. We propose that the inability of available stents to cover the "extension distance" of the bifurcation region is the cause of in-stent restenosis.The extension distance (ED) is defined as the maximal distance at the carina tip, which must be covered by the stent struts to ensure optimal coverage of the main branch (MB) and SB openings. A mathematical model was created, representing the key factors that govern geometrical reconfigurations after stent implantation in bifurcations. There are two options--with and without bifurcation region deformation. The theoretical assumptions were tested on a bifurcation model (soft polyvinylchloride polymer tubes) permitting free wall deformations and the following parameters: Parent Vessel, MB, SB diameters of 3.5, 3.0, and 2.5 mm, respectively, with an angle of 45 degrees between the MB and SB. After stenting, final KBI with 3.5 mm and 3.0 mm balloons was performed up to 20 atm.After the carina displacement, the ED, which has to be covered, is considerably smaller if the suboptimal result (DS50%) at the SB ostium is acceptable. The maximal EDs from the bench test measurements are: Vision, Abbott Vascular - 5.62 mm +/- 0.04; Liberte, Boston Scientific Corp. - 5.2 mm +/- 0.03; Chopin2, Balton - 4.58 mm +/- 0.05; Volo, Invatec - 4.41 mm +/- 0.04; Driver, Medtronics - 4.39 mm +/- 0.04; BxSonic, Cordis, JJ - 4.48 mm +/- 0.05. The theoretical maximal ED of the model is 6.91 mm-28-62% larger than actually observed with different stents.The achievement of perfect ostial coverage of the SB is unsatisfactory with most of the currently available stents, especially when poststenting excessive dilation of the ostium of the SB is performed.

Guidelines and Expert Consensus Documents summarize and evaluate all available evidence with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on outcome and the risk–benefit ratio of diagnostic or therapeutic means. Guidelines are no substitutes for textbooks and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s). The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules). Members of this Task Force were selected by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) to represent all physicians involved with the medical and surgical care of patients with coronary artery disease (CAD). A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for society are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The members of the Task Force have provided disclosure statements of all relationships that might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at European Heart House, headquarters of the ESC. Any changes in conflict of interest that arose during the writing period were notified to the ESC. The Task Force report received its entire financial support from the ESC and EACTS, without any involvement of the pharmaceutical, device, or surgical industry. ESC …

The two main problems unresolved in coronary bifurcation stenting are periprocedural side branch compromise and higher restenosis at long term. The purpose of this study is to reveal the link between periprocedural side branch compromise and long-term results after main vessel stenting only in coronary bifurcations.Eighty-four patients formed the study population. The inclusion criteria were good-quality angiograms, with maximal between-branch angle opening, no overlap, permitting accurate angiographic analysis. Carina angle (alpha)-the distal angle between main vessel (MV) before bifurcation and side branch (SB)-was measured pre- and poststenting. Clinical follow-up 9-12 months was obtained with coronary angiography if needed.The patient population was high-risk with 33% diabetics and 84% two- and three-vessel disease. Ninety-five stents were implanted in 92 lesions, with three T-stenting cases. Drug-eluting stents were implanted in 54%. Kissing-balloon (KBI) or sequential inflation was performed in 35%. SB functional closure occurred in 17.4%, with independent predictors alpha40 degrees and diameter ratio MB/SB1.22. After 12+/-4 months there were five myocardial infarctions (6%) and 13 (15%) target lesion revascularization procedures. Independent predictors of major cardiovascular events were carina angle40 degrees , MB lesion length8 mm, negative change of between-branch angle, DES usage, and KBI.Smaller carina angle with straightening of MV-main branch from stent implantation in coronary bifurcations predicted higher SB compromise, restenosis, and MACE rates during follow-up of 1 year.

We selected 5 oncogenes with well-established roles in carcinogenesis -- CCND1, ErbB1, ErbB2, c-myc and ZNF217 -- to investigate the coexistence of their copy imbalances in relation to the clinico-pathological characteristics of ovarian tumors.Fluorescence in situ hybridization for the 5 genes was applied to a preexisting tissue microarray. 38 ovarian tumors were successfully analyzed for copy number changes of the 5 genes.At least one of these oncogenes was gained/amplified in 27 out of 38 tumors (71.1%). We report the highest frequency of c-myc genetic gain/amplification since it affected 42.1% of the ovarian tumors. We observed sequential involvement of copy number alterations of the other genes in the presence of c-myc disruption. The incidence of copy number changes of the 5 oncogenes -- both single and combinatorial -- was higher in high-grade tumors. All double aberrations in the serous group comprised c-myc and ZNF217copy number increases.Our results revealed a combination between copy number increases of c-myc and ZNF217, associated with serous histology. The data from this combined analysis of the 5 oncogenes could be used as a basis in considering the combined approach in molecular-based therapy of ovarian cancer.

This study aimed to clarify the molecular mechanisms involved in ovarian carcinogenesis, and to identify candidate molecular targets for its diagnosis and treatment. The genome-wide gene expression profiles of 22 epithelial ovarian carcinomas were analyzed with a microarray representing 38,500 genes, in combination with laser microbeam microdissection. A total of 273 commonly up-regulated transcripts and 387 down-regulated transcripts were identified in the ovarian carcinoma samples. Of the 273 up-regulated transcripts, only 87 (31.9%) were previously reported as up-regulated in microarray studies using bulk cancer tissues and normal ovarian tissues for analysis. CHMP4C (chromatin-modifying protein 4C) was frequently overexpressed in ovarian carcinoma tissue, but not expressed in the normal human tissues used as a control. Our data should contribute to an improved understanding of tumorigenesis in ovarian cancer, and aid in the development of diagnostic tumor markers and molecular-targeting therapy for patients with the disease.

catheterisation laboratory: the no-reflow phenomenon and coronary perforations Olivier Muller1, MD PhD; Stephan Windecker2, MD; Thomas Cuisset3, MD; Jean Fajadet4, MD; Mark Mason5, MD; Andrea Zuffi6, MD; Alexander Doganov7, MD; Eric Eeckhout6, MD PhD 1. Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium; 2. Department of Cardiology, University Hospital Bern, Bern, Switzerland; 3. Department of Cardiology, University Hospital La Timone, Marseille, France; 4. Unite de Cardiologie Interventionnelle, Clinique Pasteur, Toulouse, France; 5. Harefield Hospital, Royal Brompton and Harefield NHS Trust, Middlesex, United Kingdom; 6. Service de Cardiologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; 7. National Heart Institute, Sofia, Bulgaria

Endometrial cancer (EC) is the most common malignancy of the female reproductive system in the industrialized world. Similar to other common diseases, gene variations are believed to be able to alter an individual's predisposition to developing the disease. The CHEK2 gene encodes a tumor suppressor that takes part in various cell processes, including cell cycle regulation, DNA repair, and apoptosis. The polymorphic variant Ile157Thr in exon 3 of the gene has been demonstrated to enhance the risk of several types of cancer and at the same time to reduce the risk for developing other cancer types. To study the significance of CHEK2 I157T for EC, we have genotyped 268 patients and 449 female controls. We found carriers of I157T more often among controls than we did among patients (2.45% vs. 1.75%), but the difference was not statistically significant. Case-only analysis revealed that the variant is overrepresented in patients diagnosed at 75 or more years of age (9.09%, p = 0.05) and in those with deep myometrial invasion (3.85%, p = 0.06). The highest frequency was observed in patients with both the aforementioned characteristics (20%, p = 0.01). Tumors of I157T carriers showed endometrioid, clear cell, and mucinous morphology, which suggested that the variant may not be restricted to a certain histotype of the disease and could even be overrepresented in rare ones. This study is the first to explore the association between germline CHEK2 I157T and EC. It suggests the need for further large-scale evaluation of the role this variant plays in endometrial carcinogenesis.

The objective of this study was to assess the implication of copy number changes of epidermal growth factor receptor (EGFR) and erbB2 genes in the etiology and progression of ovarian tumors. In our study, we used the highly reliable method of fluorescent in situ hybridization, applied on tissue microarray, containing 1006 ovarian tumors from different malignancy, histologic type and grade, and tumor stage, in order to analyze the correlations between gene copy number changes and tumor phenotype. We established copy number changes of erbB2 in 15.30% of malignant ovarian tumors-8.16% amplifications and 7.14% gains. The frequency of EGFR copy number changes was 10.67%-3.65% amplifications and 7.02% gains. EGFR gains occurred with approximately the same frequency in malignant (7.02%), low malignant potential (8.33%), and benign (7.19%) ovarian tumors. ErbB2 amplification was associated with clear cell type of ovarian cancer (P0.04). No amplification of EGFR and erbB2 genes was established in tumors with low malignant potency and in benign tumors. Regarding cancer phenotype, there was no statistically significant association between erbB2 copy number changes and histologic grade as well as tumor stage of ovarian cancer. EGFR gains are early events in ovarian tumorigenesis. Our results showed similar frequencies of EGFR gains in different grade tumors, while EGFR amplification increased from grades 1 to 2 to 3.