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Showing papers by "Katholieke Universiteit Leuven published in 2013"


Journal ArticleDOI
TL;DR: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the management of Arterspertension of the European Society ofhypertension (ESH) and of theEuropean Society of Cardiology (ESC).
Abstract: Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones. Some of the most important differences are listed below: 1. Epidemiological data on hypertension and BP control in Europe. 2. Strengthening of the prognostic value of home blood pressure monitoring (HBPM) and of its role for diagnosis and management of hypertension, next to ambulatory blood pressure monitoring (ABPM). 3. Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension. 4. Re-emphasis on integration of BP, cardiovascular (CV) risk factors, asymptomatic organ damage (OD) and clinical complications for total CV risk assessment. 5. Update of the prognostic significance of asymptomatic OD, including heart, blood vessels, kidney, eye and brain. 6. Reconsideration of the risk of overweight and target body mass index (BMI) in hypertension. 7. Hypertension in young people. 8. Initiation of antihypertensive treatment. More evidence-based criteria and no drug treatment of high normal BP. 9. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (<140 mmHg) in both higher and lower CV risk patients. 10. Liberal approach to initial monotherapy, without any all-ranking purpose. 11. Revised schema for priorital two-drug combinations. 12. New therapeutic algorithms for achieving target BP. 13. Extended section on therapeutic strategies in special conditions. 14. Revised recommendations on treatment of hypertension in the elderly. 15. Drug treatment of octogenarians. 16. Special attention to resistant hypertension and new treatment approaches. 17. Increased attention to OD-guided therapy. 18. New approaches to chronic management of hypertensive disease

7,018 citations


Journal ArticleDOI
TL;DR: In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased.
Abstract: BACKGROUND In a phase 1–2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer. METHODS We randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate. RESULTS A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel–gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel–gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel–gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel–gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel–gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days. CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. (Funded by Celgene; ClinicalTrials.gov number, NCT00844649.)

4,894 citations


Journal ArticleDOI
01 Feb 2013-Science
TL;DR: Although not yet providing compelling mechanical strength or electrical or thermal conductivities for many applications, CNT yarns and sheets already have promising performance for applications including supercapacitors, actuators, and lightweight electromagnetic shields.
Abstract: Worldwide commercial interest in carbon nanotubes (CNTs) is reflected in a production capacity that presently exceeds several thousand tons per year. Currently, bulk CNT powders are incorporated in diverse commercial products ranging from rechargeable batteries, automotive parts, and sporting goods to boat hulls and water filters. Advances in CNT synthesis, purification, and chemical modification are enabling integration of CNTs in thin-film electronics and large-area coatings. Although not yet providing compelling mechanical strength or electrical or thermal conductivities for many applications, CNT yarns and sheets already have promising performance for applications including supercapacitors, actuators, and lightweight electromagnetic shields.

4,596 citations


Journal ArticleDOI
TL;DR: Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer.
Abstract: A b s t r ac t Background Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. Methods In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. Results The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progressionfree survival was 16.5 months with abiraterone–prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone–prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone–prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P = 0.01) but did not cross the efficacy boundary. Abiraterone–predni sone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone–prednisone. Conclusions Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.)

2,315 citations


Journal ArticleDOI
TL;DR: Evidence is provided for a continuing role of targeted treatment after disease progression, with regorafenib offering a potential new line of therapy in this treatment-refractory population of patients with metastatic colorectal cancer.

2,171 citations


Journal ArticleDOI
TL;DR: The plant microbiota emerges as a fundamental trait that includes mutualism enabled through diverse biochemical mechanisms, as revealed by studies on plant growth- Promoting and plant health-promoting bacteria.
Abstract: Plants host distinct bacterial communities on and inside various plant organs, of which those associated with roots and the leaf surface are best characterized. The phylogenetic composition of these communities is defined by relatively few bacterial phyla, including Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. A synthesis of available data suggests a two-step selection process by which the bacterial microbiota of roots is differentiated from the surrounding soil biome. Rhizodeposition appears to fuel an initial substrate-driven community shift in the rhizosphere, which converges with host genotype–dependent finetuning of microbiota profiles in the selection of root endophyte assemblages. Substrate-driven selection also underlies the establishment of phyllosphere communities but takes place solely at the immediate leaf surface. Both the leaf and root microbiota contain bacteria that provide indirect pathogen protection, but root microbiota members appear to serve additional host functions through the acquisition of nutrients from soil for plant growth. Thus, the plant microbiota emerges as a fundamental trait that includes mutualism enabled through diverse biochemical mechanisms, as revealed by studies on plant growth–promoting and plant health–promoting bacteria.

2,169 citations



Journal ArticleDOI
TL;DR: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis and the frequency of adverse events was similar in the vedolIZumab and placebo groups.
Abstract: We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 pa tients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a de crease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Results Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P 1), as compared with 15.9% of pa tients who switched to placebo (adjusted difference, 26.1 percentage points for vedoliz umab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups. Conclusions Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.)

2,071 citations


Journal ArticleDOI
TL;DR: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolIZumab (rather than switching to placebo) were morelikely to be in remission at week 52.
Abstract: BackgroundUstekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. MethodsWe randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 w...

2,059 citations


Journal ArticleDOI
TL;DR: The state of the art in preprocessing of End-of-life materials containing rare-earth elements (REEs) and the final recovery is discussed in detail in this article, where the relevance of Life Cycle Assessment (LCA) for REE recycling is emphasized.

1,718 citations


Book ChapterDOI
01 Jan 2013
TL;DR: The World Reference Base for Soil Resources (WRB) is an international soil classification system for naming soils and creating legends for soil maps as discussed by the authors, which has two hierarchical levels: the first level presents 32 Reference Soil Groups (RSGs), which are identified using a key.
Abstract: World Reference Base for Soil Resources (WRB) is an international soil classification system for naming soils and creating legends for soil maps. It is edited by a Working Group of the International Union of Soil Sciences (IUSS). The currently valid edition is the update 2015 of the third edition 2014. WRB has two hierarchical levels: The first level presents 32 Reference Soil Groups (RSGs), which are identified using a key. RSGs are groups of soils that have undergone similar pedogenesis or have been formed from similar parent material or represent major ecological regions. In the second level, the soil names are constructed by adding a set of qualifiers to the name of the RSG. For the second level, 185 qualifiers are defined. Some can be combined with many RSGs, others with only a few or even with just one. The qualifiers available for use with a particular RSG are listed in the key, along with the RSG. They are divided into principal and supplementary qualifiers. The principal qualifiers are regarded to be the most significant for the further characterization of soils of the particular RSG. They are ranked and given in an order of importance. The supplementary qualifiers are not ranked but used in alphabetical order. The definitions of RSGs and qualifiers are to a certain extent based on diagnostics: Diagnostic materials are materials that significantly influence pedogenic processes. Diagnostic properties are typical results of soil-forming processes or reflect special conditions of soil formation. Diagnostic horizons are typical results of soil-forming processes, but with a minimum thickness and therefore recognizable as horizontal layers. For naming a soil, all applying qualifiers must be listed in the soil name. For map legends, generalization is required, and the number of qualifiers depends on the scale and the purpose of the map. Qualifiers may be combined with specifiers to form subqualifiers for a further speciation of the qualifiers. WRB provides codes for the RSGs, qualifiers, and specifiers and syntax rules for the combination of the codes. At the end of this article, examples are provided for naming soils and creating map legends, including the use of codes.

Journal ArticleDOI
TL;DR: The Clatterbridge Cancer Centre and Liverpool Heart and Chest Hospital, Liverpool; University of Aberdeen, Aberdeen, UK; Center for Medical Imaging, University of Groningen, Groningen; Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands; and Department of Thoracic Surgery, University Hospitals of Leicester NHS Trust, Leicester, UK.


Journal ArticleDOI
TL;DR: In this paper, the high thermal gradients occurring during SLM lead to a very fine microstructure with submicron-sized cells, which can be modified to a weak cube texture along the building and scanning directions when a rotation of 90° of the scanning vectors within or between the layers is applied.

BookDOI
TL;DR: The 4th edition of the Handbook of Research on Educational Communications and Technology expands upon the previous 3 versions, providing a comprehensive update on research pertaining to research pertaining tonew and emerging educational technologies.
Abstract: The 4th edition of the Handbook of Research on Educational Communications and Technology expands upon the previous 3 versions, providinga comprehensive updateon research pertaining tonew and emerging educational technologies. Chapters that are no longer pertinent have been eliminated in this edition, with most chapters being completely rewritten, expanded, and updated Additionally, new chapters pertaining to research methodologies in educational technologyhave been added due to expressed reader interest. Each chapter now contains an extensive literature review, documenting and explaining themost recent, outstanding research, including major findings and methodologies employed. TheHandbookauthorscontinue to beinternational leaders in their respective fields; thelist is cross disciplinary by designand great effortwas taken to invite authors outside of the traditionalinstructional design and technology community.

Proceedings ArticleDOI
01 Dec 2013
TL;DR: This paper introduces a new domain adaptation algorithm where the source and target domains are represented by subspaces described by eigenvectors, and seeks a domain adaptation solution by learning a mapping function which aligns the source subspace with the target one.
Abstract: In this paper, we introduce a new domain adaptation (DA) algorithm where the source and target domains are represented by subspaces described by eigenvectors. In this context, our method seeks a domain adaptation solution by learning a mapping function which aligns the source subspace with the target one. We show that the solution of the corresponding optimization problem can be obtained in a simple closed form, leading to an extremely fast algorithm. We use a theoretical result to tune the unique hyper parameter corresponding to the size of the subspaces. We run our method on various datasets and show that, despite its intrinsic simplicity, it outperforms state of the art DA methods.

Proceedings ArticleDOI
01 Dec 2013
TL;DR: This paper proposes fast super-resolution methods while making no compromise on quality, and supports the use of sparse learned dictionaries in combination with neighbor embedding methods, and proposes the anchored neighborhood regression.
Abstract: Recently there have been significant advances in image up scaling or image super-resolution based on a dictionary of low and high resolution exemplars. The running time of the methods is often ignored despite the fact that it is a critical factor for real applications. This paper proposes fast super-resolution methods while making no compromise on quality. First, we support the use of sparse learned dictionaries in combination with neighbor embedding methods. In this case, the nearest neighbors are computed using the correlation with the dictionary atoms rather than the Euclidean distance. Moreover, we show that most of the current approaches reach top performance for the right parameters. Second, we show that using global collaborative coding has considerable speed advantages, reducing the super-resolution mapping to a precomputed projective matrix. Third, we propose the anchored neighborhood regression. That is to anchor the neighborhood embedding of a low resolution patch to the nearest atom in the dictionary and to precompute the corresponding embedding matrix. These proposals are contrasted with current state-of-the-art methods on standard images. We obtain similar or improved quality and one or two orders of magnitude speed improvements.

Journal ArticleDOI
TL;DR: This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
Abstract: Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 10 × 10(-4)) In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 50 × 10(-8)), 3 of which we found after conditioning on previously identified variants Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals

Journal ArticleDOI
TL;DR: The historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique are considered, while the role ofABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined.
Abstract: Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both clinical practice and hypertension research. Although there are many guidelines that emphasize the indications for ABPM, there is no comprehensive guideline dealing with all aspects of the technique. It was agreed at a consensus meeting on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive position paper on the scientific evidence for ABPM.This position paper considers the historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique. It examines the need for selecting an appropriate device, the accuracy of devices, the additional information and indices that ABPM devices may provide, and the software requirements.At a practical level, the paper details the requirements for using ABPM in clinical practice, editing considerations, the number of measurements required, and the circumstances, such as obesity and arrhythmias, when particular care needs to be taken when using ABPM.The clinical indications for ABPM, among which white-coat phenomena, masked hypertension, and nocturnal hypertension appear to be prominent, are outlined in detail along with special considerations that apply in certain clinical circumstances, such as childhood, the elderly and pregnancy, and in cardiovascular illness, examples being stroke and chronic renal disease, and the place of home measurement of blood pressure in relation to ABPM is appraised.The role of ABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined and finally the implementation of ABPM in practice is considered in relation to the issue of reimbursement in different countries, the provision of the technique by primary care practices, hospital clinics and pharmacies, and the growing role of registries of ABPM in many countries.

Journal ArticleDOI
14 Aug 2013-PLOS ONE
TL;DR: Experience-sampling results suggest that Facebook may undermine well-being, rather than enhancing it, as Facebook use predicts negative shifts on both of these variables over time.
Abstract: Over 500 million people interact daily with Facebook. Yet, whether Facebook use influences subjective well-being over time is unknown. We addressed this issue using experience-sampling, the most reliable method for measuring in-vivo behavior and psychological experience. We text-messaged people five times per day for two-weeks to examine how Facebook use influences the two components of subjective well-being: how people feel moment-to-moment and how satisfied they are with their lives. Our results indicate that Facebook use predicts negative shifts on both of these variables over time. The more people used Facebook at one time point, the worse they felt the next time we text-messaged them; the more they used Facebook over two-weeks, the more their life satisfaction levels declined over time. Interacting with other people “directly” did not predict these negative outcomes. They were also not moderated by the size of people's Facebook networks, their perceived supportiveness, motivation for using Facebook, gender, loneliness, self-esteem, or depression. On the surface, Facebook provides an invaluable resource for fulfilling the basic human need for social connection. Rather than enhancing well-being, however, these findings suggest that Facebook may undermine it.

Journal ArticleDOI
TL;DR: The 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext
Abstract: 1. INTRODUCTION1.1 PrinciplesThe 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext

Journal ArticleDOI
TL;DR: Endurance, dynamic resistance, and isometric resistance training lower SBP and DBP, whereas combined training lowers only DBP.
Abstract: BackgroundWe conducted meta‐analyses examining the effects of endurance, dynamic resistance, combined endurance and resistance training, and isometric resistance training on resting blood pressure ...

Journal ArticleDOI
TL;DR: The use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications, as compared with warfarin, thus showing no benefit and an excess risk.
Abstract: Background Dabigatran is an oral direct thrombin inhibitor that has been shown to be an effective alternative to warfarin in patients with atrial fibrillation. We evaluated the use of dabigatran in patients with mechanical heart valves. Methods In this phase 2 dose-validation study, we studied two populations of patients: those who had undergone aortic- or mitral-valve replacement within the past 7 days and those who had undergone such replacement at least 3 months earlier. Patients were randomly assigned in a 2:1 ratio to receive either dabigatran or warfarin. The selection of the initial dabigatran dose (150, 220, or 300 mg twice daily) was based on kidney function. Doses were adjusted to obtain a trough plasma level of at least 50 ng per milliliter. The warfarin dose was adjusted to obtain an international normalized ratio of 2 to 3 or 2.5 to 3.5 on the basis of thromboembolic risk. The primary end point was the trough plasma level of dabigatran. Results The trial was terminated prematurely after the e...


Journal ArticleDOI
TL;DR: A meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, and identified 29,807 SNPs for further genotyping suggests that more than 1,000 additional loci are involved in breast cancer susceptibility.
Abstract: Breast cancer is the most common cancer among women Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC) The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)) Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility

MonographDOI
19 Jul 2013
TL;DR: This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats.
Abstract: Book file PDF easily for everyone and every device. You can download and read online Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition file PDF Book only if you are registered here. And also you can download or read online all Book PDF file that related with Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition book. Happy reading Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition Bookeveryone. Download file Free Book PDF Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition at Complete PDF Library. This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats. Here is The Complete PDF Book Library. It's free to register here to get Book file PDF Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition.


Journal ArticleDOI
TL;DR: Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer.
Abstract: Summary Background Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and bevacizumab-naive second-line metastatic colorectal cancer. We assessed continued use of bevacizumab plus standard second-line chemotherapy in patients with metastatic colorectal cancer progressing after standard first-line bevacizumab-based treatment. Methods In an open-label, phase 3 study in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain, Sweden, and Switzerland, patients (aged ≥18 years) with unresectable, histologically confirmed metastatic colorectal cancer progressing up to 3 months after discontinuing first-line bevacizumab plus chemotherapy were randomly assigned in a 1:1 ratio to second-line chemotherapy with or without bevacizumab 2·5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7·5 mg/kg every 3 weeks, intravenously). The choice between oxaliplatin-based or irinotecan-based second-line chemotherapy depended on the first-line regimen (switch of chemotherapy). A combination of a permuted block design and the Pocock and Simon minimisation algorithm was used for the randomisation. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00700102. Findings Between Feb 1, 2006, and June 9, 2010, 409 (50%) patients were assigned to bevacizumab plus chemotherapy and 411 (50%) to chemotherapy alone. Median follow-up was 11·1 months (IQR 6·4–15·6) in the bevacizumab plus chemotherapy group and 9·6 months (5·4–13·9) in the chemotherapy alone group. Median overall survival was 11·2 months (95% CI 10·4–12·2) for bevacizumab plus chemotherapy and 9·8 months (8·9–10·7) for chemotherapy alone (hazard ratio 0·81, 95% CI 0·69–0·94; unstratified log-rank test p=0·0062). Grade 3–5 bleeding or haemorrhage (eight [2%] vs one [ vs three [ vs 12 [3%]) were more common in the bevacizumab plus chemotherapy group than in the chemotherapy alone group. The most frequently reported grade 3–5 adverse events were neutropenia (65 [16%] in the bevacizumab and chemotherapy group vs 52 [13%] in the chemotherapy alone group), diarrhoea (40 [10%] vs 34 [8%], respectively), and asthenia (23 [6%] vs 17 [4%], respectively). Treatment-related deaths were reported for four patients in the bevacizumab plus chemotherapy group and three in the chemotherapy alone group. Interpretation Maintenance of VEGF inhibition with bevacizumab plus standard second-line chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer. This approach is also being investigated in other tumour types, including metastatic breast and non-small cell lung cancers. Funding F Hoffmann-La Roche.


Journal ArticleDOI
TL;DR: Overall survival data after long-term follow-up found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable liver metastases from colorectal cancer, however, the previously observed benefit in PFS means it should remain the reference treatment for this population of patients.
Abstract: Summary Background Previous results of the EORTC intergroup trial 40983 showed that perioperative chemotherapy with FOLFOX4 (folinic acid, fluorouracil, and oxaliplatin) increases progression-free survival (PFS) compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Here we present overall survival data after long-term follow-up. Methods This randomised, controlled, parallel-group, phase 3 study recruited patients from 78 hospitals across Europe, Australia, and Hong Kong. Eligible patients aged 18–80 years who had histologically proven colorectal cancer and up to four liver metastases were randomly assigned (1:1) to either perioperative FOLFOX4 or surgery alone. Perioperative FOLFOX4 consisted of six 14-day cycles of oxaliplatin 85mg/m 2 , folinic acid 200 mg/m 2 (DL form) or 100 mg/m 2 (L form) on days 1–2 plus bolus, and fluorouracil 400 mg/m 2 (bolus) and 600 mg/m 2 (continuous 22 h infusion), before and after surgery. Patients were centrally randomised by minimisation, adjusting for centre and risk score and previous adjuvant chemotherapy to primary surgery for colorectal cancer, and the trial was open label. Analysis of overall survival was by intention to treat in all randomly assigned patients. This trial is registered with ClinicalTrials.gov, number NCT00006479. Findings Between Oct 10, 2000, and July 5, 2004, 364 patients were randomly assigned to a treatment group (182 patients in each group, of which 171 per group were eligible and 152 per group underwent resection). At a median follow-up of 8·5 years (IQR 7·6–9·5), 107 (59%) patients in the perioperative chemotherapy group had died versus 114 (63%) in the surgery-only group (HR 0·88, 95% CI 0·68–1·14; p=0·34). In all randomly assigned patients, median overall survival was 61·3 months (95% CI 51·0–83·4) in the perioperative chemotherapy group and 54·3 months (41·9–79·4) in the surgery alone group. 5-year overall survival was 51·2% (95% CI 43·6–58·3) in the perioperative chemotherapy group versus 47·8% (40·3–55·0) in the surgery-only group. Two patients in the perioperative chemotherapy group and three in the surgery-only group died from complications of protocol surgery, and one patient in the perioperative chemotherapy group died possibly as a result of toxicity of protocol treatment. Interpretation We found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable liver metastases from colorectal cancer. However, the previously observed benefit in PFS means that perioperative chemotherapy with FOLFOX4 should remain the reference treatment for this population of patients. Funding Norwegian and Swedish Cancer Societies, Cancer Research UK, Ligue Nationale Contre Cancer, US National Cancer Institute, Sanofi-Aventis.