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Institution

VU University Amsterdam

EducationAmsterdam, Noord-Holland, Netherlands
About: VU University Amsterdam is a(n) education organization based out in Amsterdam, Noord-Holland, Netherlands. It is known for research contribution in the topic(s): Population & Poison control. The organization has 33856 authors who have published 75643 publication(s) receiving 3414264 citation(s).
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Journal ArticleDOI
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Abstract: Background An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. Methods A total of 676 HLA-A*0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. Results The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Conclusions Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

11,659 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +1008 moreInstitutions (96)
TL;DR: This is the first direct detection of gravitational waves and the first observation of a binary black hole merger, and these observations demonstrate the existence of binary stellar-mass black hole systems.
Abstract: On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of $1.0 \times 10^{-21}$. It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203 000 years, equivalent to a significance greater than 5.1 {\sigma}. The source lies at a luminosity distance of $410^{+160}_{-180}$ Mpc corresponding to a redshift $z = 0.09^{+0.03}_{-0.04}$. In the source frame, the initial black hole masses are $36^{+5}_{-4} M_\odot$ and $29^{+4}_{-4} M_\odot$, and the final black hole mass is $62^{+4}_{-4} M_\odot$, with $3.0^{+0.5}_{-0.5} M_\odot c^2$ radiated in gravitational waves. All uncertainties define 90% credible intervals.These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger.

8,011 citations


Journal ArticleDOI
Jan M. M. Walboomers1, M. V. Jacobs1, M. M. Manos2, Franz X. Bosch  +6 moreInstitutions (4)
TL;DR: The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer, and the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening.
Abstract: A recent report that 93 per cent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an underestimate, due to sample inadequacy or integration events affecting the HPV L1 gene, which is the target of the polymerase chain reaction (PCR)-based test which was used. The formerly HPV-negative cases from this study have therefore been reanalyzed for HPV serum antibodies and HPV DNA. Serology for HPV 16 VLPs, E6, and E7 antibodies was performed on 49 of the 66 cases which were HPV-negative and a sample of 48 of the 866 cases which were HPV-positive in the original study. Moreover, 55 of the 66 formerly HPV-negative biopsies were also reanalyzed by a sandwich procedure in which the outer sections in a series of sections are used for histological review, while the inner sections are assayed by three different HPV PCR assays targeting different open reading frames (ORFs). No significant difference was found in serology for HPV 16 proteins between the cases that were originally HPV PCR-negative and -positive. Type-specific E7 PCR for 14 high-risk HPV types detected HPV DNA in 38 (69 per cent) of the 55 originally HPV-negative and amplifiable specimens. The HPV types detected were 16, 18, 31, 33, 39, 45, 52, and 58. Two (4 per cent) additional cases were only HPV DNA-positive by E1 and/or L1 consensus PCR. Histological analysis of the 55 specimens revealed that 21 were qualitatively inadequate. Only two of the 34 adequate samples were HPV-negative on all PCR tests, as against 13 of the 21 that were inadequate ( p< 0.001). Combining the data from this and the previous study and excluding inadequate specimens, the worldwide HPV prevalence in cervical carcinomas is 99.7 per cent. The presence of HPV in virtually all cervical cancers implies the highest worldwide attributable fraction so far reported for a specific cause of any major human cancer. The extreme rarity of HPV-negative cancers reinforces the rationale for HPV testing in addition to, or even instead of, cervical cytology in routine cervical screening.

7,930 citations


Journal ArticleDOI
TL;DR: The “Activation‐strain TS interaction” (ATS) model of chemical reactivity is reviewed as a conceptual framework for understanding how activation barriers of various types of reaction mechanisms arise and how they may be controlled, for example, in organic chemistry or homogeneous catalysis.
Abstract: We present the theoretical and technical foundations of the Amsterdam Density Functional (ADF) program with a survey of the characteristics of the code (numerical integration, density fitting for the Coulomb potential, and STO basis functions). Recent developments enhance the efficiency of ADF (e.g., parallelization, near order-N scaling, QM/MM) and its functionality (e.g., NMR chemical shifts, COSMO solvent effects, ZORA relativistic method, excitation energies, frequency-dependent (hyper)polarizabilities, atomic VDD charges). In the Applications section we discuss the physical model of the electronic structure and the chemical bond, i.e., the Kohn–Sham molecular orbital (MO) theory, and illustrate the power of the Kohn–Sham MO model in conjunction with the ADF-typical fragment approach to quantitatively understand and predict chemical phenomena. We review the “Activation-strain TS interaction” (ATS) model of chemical reactivity as a conceptual framework for understanding how activation barriers of various types of (competing) reaction mechanisms arise and how they may be controlled, for example, in organic chemistry or homogeneous catalysis. Finally, we include a brief discussion of exemplary applications in the field of biochemistry (structure and bonding of DNA) and of time-dependent density functional theory (TDDFT) to indicate how this development further reinforces the ADF tools for the analysis of chemical phenomena. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 931–967, 2001

7,613 citations


Journal ArticleDOI
Marco Dorigo1, Luca Maria Gambardella2Institutions (2)
TL;DR: The results show that the ACS outperforms other nature-inspired algorithms such as simulated annealing and evolutionary computation, and it is concluded comparing ACS-3-opt, a version of the ACS augmented with a local search procedure, to some of the best performing algorithms for symmetric and asymmetric TSPs.
Abstract: This paper introduces the ant colony system (ACS), a distributed algorithm that is applied to the traveling salesman problem (TSP). In the ACS, a set of cooperating agents called ants cooperate to find good solutions to TSPs. Ants cooperate using an indirect form of communication mediated by a pheromone they deposit on the edges of the TSP graph while building solutions. We study the ACS by running experiments to understand its operation. The results show that the ACS outperforms other nature-inspired algorithms such as simulated annealing and evolutionary computation, and we conclude comparing ACS-3-opt, a version of the ACS augmented with a local search procedure, to some of the best performing algorithms for symmetric and asymmetric TSPs.

7,152 citations


Authors

Showing all 33856 results

NameH-indexPapersCitations
Albert Hofman2672530321405
Raymond J. Dolan196919138540
Cornelia M. van Duijn1831030146009
Paul M. Thompson1832271146736
David A. Weitz1781038114182
Dorret I. Boomsma1761507136353
Brenda W.J.H. Penninx1701139119082
Kaj Blennow1601845116237
Vilmundur Gudnason159837123802
Lex M. Bouter158767103034
Wolfgang Wagner1562342123391
Frederik Barkhof1541449104982
Harry Campbell150897115457
Walter Paulus14980986252
James F. Wilson146677101883
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202274
20214,966
20204,640
20194,183
20183,507
20173,711

Top Attributes

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Institution's top 5 most impactful journals

Social Science Research Network

2K papers, 37.7K citations

PLOS ONE

785 papers, 32K citations

bioRxiv

584 papers, 3.9K citations

Research Papers in Economics

343 papers, 3.1K citations

Physical Review Letters

334 papers, 47.5K citations