Showing papers by "Ghent University published in 2006"

Expert consensus document on arterial stiffness: methodological issues and clinical applications

Abstract: In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.

The genome of black cottonwood, Populus trichocarpa (Torr. & Gray)

Abstract: We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.

Classification criteria for psoriatic arthritis: Development of new criteria from a large international study

Abstract: Objective To compare the accuracy of existing classification criteria for the diagnosis of psoriatic arthritis (PsA) and to construct new criteria from observed data. Methods Data were collected prospectively from consecutive clinic attendees with PsA and other inflammatory arthropathies. Subjects were classified by each of 7 criteria. Sensitivity and specificity were compared using conditional logistic regression analysis. Latent class analysis was used to calculate criteria accuracy in order to confirm the validity of clinical diagnosis as the gold standard definition of “case”-ness. Classification and Regression Trees methodology and logistic regression were used to identify items for new criteria, which were then constructed using a receiver operating characteristic curve. Results Data were collected on 588 cases and 536 controls with rheumatoid arthritis (n = 384), ankylosing spondylitis (n = 72), undifferentiated arthritis (n = 38), connective tissue disorders (n = 14), and other diseases (n = 28). The specificity of each set of criteria was high. The sensitivity of the Vasey and Espinoza method (0.97) was similar to that of the method of McGonagle et al (0.98) and greater than that of the methods of Bennett (0.44), Moll and Wright (0.91), the European Spondylarthropathy Study Group (0.74), and Gladman et al (0.91). The CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria consisted of established inflammatory articular disease with at least 3 points from the following features: current psoriasis (assigned a score of 2; all other features were assigned a score of 1), a history of psoriasis (unless current psoriasis was present), a family history of psoriasis (unless current psoriasis was present or there was a history of psoriasis), dactylitis, juxtaarticular new bone formation, rheumatoid factor negativity, and nail dystrophy. These criteria were more specific (0.987 versus 0.960) but less sensitive (0.914 versus 0.972) than those of Vasey and Espinoza. Conclusion The CASPAR criteria are simple and highly specific but less sensitive than the Vasey and Espinoza criteria.

Insights into social insects from the genome of the honeybee Apis mellifera

Abstract: Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis.

Abstract: The lack of a standard definition for acute kidney injury has resulted in a large variation in the reported incidence and associated mortality RIFLE, a newly developed international consensus classification for acute kidney injury, defines three grades of severity – risk (class R), injury (class I) and failure (class F) – but has not yet been evaluated in a clinical series We performed a retrospective cohort study, in seven intensive care units in a single tertiary care academic center, on 5,383 patients admitted during a one year period (1 July 2000–30 June 2001) Acute kidney injury occurred in 67% of intensive care unit admissions, with maximum RIFLE class R, class I and class F in 12%, 27% and 28%, respectively Of the 1,510 patients (28%) that reached a level of risk, 840 (56%) progressed Patients with maximum RIFLE class R, class I and class F had hospital mortality rates of 88%, 114% and 263%, respectively, compared with 55% for patients without acute kidney injury Additionally, acute kidney injury (hazard ratio, 17; 95% confidence interval, 128–213; P < 0001) and maximum RIFLE class I (hazard ratio, 14; 95% confidence interval, 102–188; P = 0037) and class F (hazard ratio, 27; 95% confidence interval, 203–355; P < 0001) were associated with hospital mortality after adjusting for multiple covariates In this general intensive care unit population, acute kidney 'risk, injury, failure', as defined by the newly developed RIFLE classification, is associated with increased hospital mortality and resource use Patients with RIFLE class R are indeed at high risk of progression to class I or class F Patients with RIFLE class I or class F incur a significantly increased length of stay and an increased risk of inhospital mortality compared with those who do not progress past class R or those who never develop acute kidney injury, even after adjusting for baseline severity of illness, case mix, race, gender and age

Aneurysm Syndromes Caused by Mutations in the TGF-β Receptor

Abstract: Background The Loeys–Dietz syndrome is a recently described autosomal dominant aortic-aneurysm syndrome with widespread systemic involvement The disease is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is caused by heterozygous mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2, respectively) Methods We undertook the clinical and molecular characterization of 52 affected families Forty probands presented with typical manifestations of the Loeys–Dietz syndrome In view of the phenotypic overlap between this syndrome and vascular Ehlers–Danlos syndrome, we screened an additional cohort of 40 patients who had vascular Ehlers–Danlos syndrome without the characteristic type III collagen abnormalities or the craniofacial features of the Loeys–Dietz syndrome Results We found a mutation in TGFBR1 or TGFBR2 in all probands with typical Loeys–Dietz syndrome (type I) and in 12 probands presenting

Automaticity: A Theoretical and Conceptual Analysis.

Abstract: Several theoretical views of automaticity are discussed. Most of these suggest that automaticity should be diagnosed by looking at the presence of features such as unintentional, uncontrolled/uncontrollable, goal independent, autonomous, purely stimulus driven, unconscious, efficient, and fast. Contemporary views further suggest that these features should be investigated separately. The authors examine whether features of automaticity can be disentangled on a conceptual level, because only then is the separate investigation of them worth the effort. They conclude that the conceptual analysis of features is to a large extent feasible. Not all researchers agree with this position, however. The authors show that assumptions of overlap among features are determined by the other researchers’ views of automaticity and by the models they endorse for information processing in general.

Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages

Abstract: Gram-negative bacteria that replicate in the cytosol of mammalian macrophages can activate a signaling pathway leading to caspase-1 cleavage and secretion of interleukin 1beta, a powerful host response factor. Ipaf, a cytosolic pattern-recognition receptor in the family of nucleotide-binding oligomerization domain-leucine-rich repeat proteins, is critical in such a response to salmonella infection, but the mechanism of how Ipaf is activated by the bacterium remains poorly understood. Here we demonstrate that salmonella strains either lacking flagellin or expressing mutant flagellin were deficient in activation of caspase-1 and in interleukin 1beta secretion, although transcription factor NF-kappaB-dependent production of interleukin 6 or the chemokine MCP-1 was unimpaired. Delivery of flagellin to the macrophage cytosol induced Ipaf-dependent activation of caspase-1 that was independent of Toll-like receptor 5, required for recognition of extracellular flagellin. In macrophages made tolerant by previous exposure to lipopolysaccharide, which abrogates activation of NF-kappaB and mitogen-activated protein kinases, salmonella infection still activated caspase-1. Thus, detection of flagellin through Ipaf induces caspase-1 activation independently of Toll-like receptor 5 in salmonella-infected and lipopolysaccharide-tolerized macrophages.

Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3

Abstract: Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle-Wells syndrome and neonatal-onset multiple-system inflammatory disease. Cryopyrin (also called Nalp3), the product of CIAS1, is a member of the NOD-LRR protein family that has been linked to the activation of intracellular host defence signalling pathways. Cryopyrin forms a multi-protein complex termed 'the inflammasome', which contains the apoptosis-associated speck-like protein (ASC) and caspase-1, and promotes caspase-1 activation and processing of pro-interleukin (IL)-1beta (ref. 4). Here we show the effect of cryopyrin deficiency on inflammasome function and immune responses. Cryopyrin and ASC are essential for caspase-1 activation and IL-1beta and IL-18 production in response to bacterial RNA and the imidazoquinoline compounds R837 and R848. In contrast, secretion of tumour-necrosis factor-alpha and IL-6, as well as activation of NF-kappaB and mitogen-activated protein kinases (MAPKs) were unaffected by cryopyrin deficiency. Furthermore, we show that Toll-like receptors and cryopyrin control the secretion of IL-1beta and IL-18 through different intracellular pathways. These results reveal a critical role for cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1, and provide insights regarding the pathogenesis of autoinflammatory syndromes.

Content analysis schemes to analyze transcripts of online asynchronous discussion groups: a review

Abstract: Research in the field of Computer Supported Collaborative Learning (CSCL) is based on a wide variety of methodologies. In this paper, we focus upon content analysis, which is a technique often used to analyze transcripts of asynchronous, computer mediated discussion groups in formal educational settings. Although this research technique is often used, standards are not yet established. The applied instruments reflect a wide variety of approaches and differ in their level of detail and the type of analysis categories used. Further differences are related to a diversity in their theoretical base, the amount of information about validity and reliability, and the choice for the unit of analysis. This article presents an overview of different content analysis instruments, building on a sample of models commonly used in the CSCL-literature. The discussion of 15 instruments results in a number of critical conclusions. There are questions about the coherence between the theoretical base and the operational translation of the theory in the instruments. Instruments are hardly compared or contrasted with one another. As a consequence the empirical base of the validity of the instruments is limited. The analysis is rather critical when it comes to the issue of reliability. The authors put forward the need to improve the theoretical and empirical base of the existing instruments in order to promote the overall quality of CSCL-research.

Comet 81P/Wild 2 under a microscope.

Abstract: The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.

Continuous Electricity Generation at High Voltages and Currents Using Stacked Microbial Fuel Cells

Abstract: Connecting several microbial fuel cell (MFC) units in series or parallel can increase voltage and current; the effect on the microbial electricity generation was as yet unknown Six individual continuous MFC units in a stacked configuration produced a maximum hourly averaged power output of 258 W m(-3) using a hexacyanoferrate cathode The connection of the 6 MFC units in series and parallel enabled an increase of the voltages (202 V at 228 W m(-3)) and the currents (255 mA at 248 W m(-3)), while retaining high power outputs During the connection in series, the individual MFC voltages diverged due to microbial limitations at increasing currents With time, the initial microbial community decreased in diversity and Gram-positive species became dominant The shift of the microbial community accompanied a tripling of the short time power output of the individual MFCs from 73 W m(-3) to 275 W m(-3), a decrease of the mass transfer limitations and a lowering of the MFC internal resistance from 65 +/- 10 to 39 +/- 05 omega This study demonstrates a clear relation between the electrochemical performance and the microbial composition of MFCs and further substantiates the potential to generate useful energy by means of MFCs

Investigating the Impact of Firm Size on Small Business Social Responsibility: A Critical Review

Abstract: The impact of smaller firm size on corporate social responsibility (CSR) is ambiguous. Some contend that small businesses are socially responsible by nature, while others argue that a smaller firm size imposes barriers on small firms that constrain their ability to take responsible action. This paper critically analyses recent theoretical and empirical contributions on the size-social responsibility relationship among small businesses. More specifically, it reviews the impact of firm size on four antecedents of business behaviour: issue characteristics, personal characteristics, organizational characteristics and context characteristics. It concludes that the small business context does impose barriers on social responsibility taking, but that the impact of the smaller firm size on social responsibility should be nuanced depending on a number of conditions. From a critical analysis of these conditions, opportunities for small businesses and their constituents to overcome the constraining barriers are suggested.

Reactive Oxygen Species in Plant Cell Death

Abstract: Paradoxically, death is an integral part of life. Cell death is essential for growth and development of eukaryotes, by maintaining tissue and organ homeostasis in concert with cell proliferation, growth, and differentiation. Until recently, the wide variety of cell death types reported in the

Cell cycle regulation in plant development.

Abstract: Cell cycle regulation is of pivotal importance for plant growth and development. Although plant cell division shares basic mechanisms with all eukaryotes, plants have evolved novel molecules orchestrating the cell cycle. Some regulatory proteins, such as cyclins and inhibitors of cyclin-dependent kinases, are particularly numerous in plants, possibly reflecting the remarkable ability of plants to modulate their postembryonic development. Many plant cells also can continue DNA replication in the absence of mitosis, a process known as endoreduplication, causing polyploidy. Here, we review the molecular mechanisms that regulate cell division and endoreduplication and we discuss our understanding, albeit very limited, on how the cell cycle is integrated with plant development.

Transcriptomic Footprints Disclose Specificity of Reactive Oxygen Species Signaling in Arabidopsis

Abstract: Reactive oxygen species (ROS) are key players in the regulation of plant development, stress responses, and programmed cell death. Previous studies indicated that depending on the type of ROS (hydrogen peroxide, superoxide, or singlet oxygen) or its subcellular production site (plastidic, cytosolic, peroxisomal, or apoplastic), a different physiological, biochemical, and molecular response is provoked. We used transcriptome data generated from ROS-related microarray experiments to assess the specificity of ROS-driven transcript expression. Data sets obtained by exogenous application of oxidative stress-causing agents (methyl viologen, Alternaria alternata toxin, 3-aminotriazole, and ozone) and from a mutant (fluorescent) and transgenic plants, in which the activity of an individual antioxidant enzyme was perturbed (catalase, cytosolic ascorbate peroxidase, and copper/ zinc superoxide dismutase), were compared. In total, the abundance of nearly 26,000 transcripts of Arabidopsis (Arabidopsis thaliana) was monitored in response to different ROS. Overall, 8,056, 5,312, and 3,925 transcripts showed at least a 3-, 4-, or 5-fold change in expression, respectively. In addition to marker transcripts that were specifically regulated by hydrogen peroxide, superoxide, or singlet oxygen, several transcripts were identified as general oxidative stress response markers because their steady-state levels were at least 5-fold elevated in most experiments. We also assessed the expression characteristics of all annotated transcription factors and inferred new candidate regulatory transcripts that could be responsible for orchestrating the specific transcriptomic signatures triggered by different ROS. Our analysis provides a framework that will assist future efforts to address the impact of ROS signals within environmental stress conditions and elucidate the molecular mechanisms of the oxidative stress response in plants.

Grating Couplers for Coupling between Optical Fibers and Nanophotonic Waveguides

Abstract: Nanophotonic waveguides and components are promising for use in the large-scale integration of photonic circuits. Coupling light between nanophotonic waveguides and a single-mode fiber is an important problem and many different solutions have been proposed and demonstrated in recent years. In this paper, we discuss a grating coupler approach. Grating couplers can be placed anywhere on a circuit and can easily be integrated. We have experimentally demonstrated >30% coupling efficiency with a 1 dB bandwidth of 40 nm on standard wafers. Theoretically, the coupling efficiency can be improved to >90% using an optimized grating design and layer stack. The fabrication of the couplers in silicon-on-insulator and in indium phosphide membranes is also discussed.

Differentiation of chronic sinus diseases by measurement of inflammatory mediators.

Abstract: Background: Chronic rhinosinusitis (CRS) clinically is a heterogeneous group of sinus diseases, which may cover different disease entities, or may represent a disease continuum. Studying inflammatory cells and mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases. Methods: Sinonasal mucosal tissue from 10 nasal polyp (NP) patients, 13 cystic fibrosis patients (CF-NP), eight CRS subjects without polyps, and nine control patients were stained for CD3, CD25, CD68, CD20, myeloperoxidase (MPO), CD138 and tissue homogenates were assayed for eotaxin, interleukin (IL)-1 beta, IL-2sR alpha, IL-5, interferon (IFN)-gamma, IL-8, transforming growth factor (TGF)-beta 1, tumor necrosis factor-alpha, and MPO by enzyme-linked immunosorbent assay or UNICAP system. Results: Nasal polyp and CF-NP showed increased numbers and activation of T cells, while only NP displayed an increase in plasma cells. Nasal polyp had significantly higher levels of eosinophilic markers [eosinophils, eotaxin, and eosinophil cationic protein (ECP)] compared with CRS, controls and CF-NP. Chronic rhinosinusitis was characterized by a Th1 polarization with high levels of IFN-gamma and TGF-beta, while NP showed a Th2 polarization with high IL-5 and immunoglobulin (Ig) E concentrations. Nasal polyp and CF-NP were discriminated by edema from CRS and controls, with CF-NP displaying a very prominent neutrophilic inflammation. Conclusions: Based on cellular and mediator profiles, we suggest that CRS, NP, and CF-NP are distinct disease entities within the group of chronic sinus diseases.

35 years of studies on business failure: an overview of the classic statistical methodologies and their related problems

Abstract: Over the last 35 years, business failure prediction has become a major research domain within corporate finance. Numerous corporate failure prediction models have been developed, based on various modelling techniques. The most popular are the classic cross-sectional statistical methods, which have resulted in various ‘single-period’ or static models, especially multivariate discriminant models and logit models. To date, there has been no clear overview and discussion of the application of classic statistical methods to business failure prediction. Therefore, this paper extensively elaborates on the application of (1) univariate analysis, (2) risk index models, (3) multivariate discriminant analysis, and (4) conditional probability models in corporate failure prediction. In addition, because there is no clear and comprehensive analysis in the existing literature of the diverse problems related to the application of these methods to the topic of corporate failure prediction, this paper brings together all problem issues and enlarges upon each of them. It discusses all problems related to: (1) the classical paradigm (i.e. the arbitrary definition of failure, non-stationarity and data instability, sampling selectivity, and the choice of the optimisation criteria); (2) the neglect of the time dimension of failure; and (3) the application focus in failure prediction modelling. Further, the paper elaborates on a number of other problems related to the use of a linear classification rule, the use of annual account information, and neglect of the multidimensional nature of failure. This paper contributes towards a thorough understanding of the features of the classic statistical business failure prediction models and their related problems.

Probing the Lewis acidity and catalytic activity of the metal-organic framework [Cu3(btc)2] (BTC=benzene-1,3,5-tricarboxylate).

Abstract: An optimized procedure was designed for the preparation of the microporous metal-organic framework (MOF) [Cu3(btc)2] (BTC=benzene-1,3,5-tricarboxylate). The crystalline material was characterized by X-ray diffraction, optical microscopy, SEM, X-ray photoelectron spectroscopy, N2 sorption, thermogravimetry, and IR spectroscopy of adsorbed CO. CO adsorbs on a small number of Cu2O impurities, and particularly on the free CuII coordination sites in the framework. [Cu3(btc)2] is a highly selective Lewis acid catalyst for the isomerization of terpene derivatives, such as the rearrangement of alpha-pinene oxide to campholenic aldehyde and the cyclization of citronellal to isopulegol. By using the ethylene ketal of 2-bromopropiophenone as a test substrate, it was demonstrated that the active sites in [Cu3(btc)2] are hard Lewis acids. Catalyst stability, re-usability, and heterogeneity are critically assessed.

Quenching and partitioning martensite-a novel steel heat treatment

Abstract: A novel concept for the heat treatment of martensite, different to customary quenching and tempering, is described. This involves quenching to below the martensite-start temperature and directly ageing, either at, or above, the initial quench temperature. If competing reactions, principally carbide precipitation, are suppressed by appropriate alloying, the carbon partitions from the supersaturated martensite phase to the untransformed austenite phase, thereby increasing the stability of the residual austenite upon subsequent cooling to room temperature. This novel treatment has been termed ‘quenching and partitioning’ (Q&P), to distinguish it from quenching and tempering, and can be used to generate microstructures with martensite/austenite combinations giving attractive properties. Another approach that has been used to produce austenite-containing microstructures is by alloying to suppress carbide precipitation during the formation of bainitic structures, and interesting comparisons can be made between the two approaches. Moreover, formation of carbide-free bainite during the Q&P partitioning treatment may be a reaction competing for carbon, although this could also be used constructively as an additional stage of Q&P partitioning to form part of the final microstructure. Amongst the ferrous alloys examined so far are medium carbon bar steels and low carbon formable TRIP-assisted sheet steels.

Chemical composition of secondary organic aerosol formed from the photooxidation of isoprene

Abstract: Recent work in our laboratory has shown that the photooxidation of isoprene (2-methyl-1,3-butadiene, C(5)H(8)) leads to the formation of secondary organic aerosol (SOA) In the current study, the chemical composition of SOA from the photooxidation of isoprene over the full range of NO(x) conditions is investigated through a series of controlled laboratory chamber experiments SOA composition is studied using a wide range of experimental techniques: electrospray ionization-mass spectrometry, matrix-assisted laser desorption ionization-mass spectrometry, high-resolution mass spectrometry, online aerosol mass spectrometry, gas chromatography/mass spectrometry, and an iodometric-spectroscopic method Oligomerization was observed to be an important SOA formation pathway in all cases; however, the nature of the oligomers depends strongly on the NO(x) level, with acidic products formed under high-NO(x) conditions only We present, to our knowledge, the first evidence of particle-phase esterification reactions in SOA, where the further oxidation of the isoprene oxidation product methacrolein under high-NO(x) conditions produces polyesters involving 2-methylglyceric acid as a key monomeric unit These oligomers comprise approximately 22-34% of the high-NO(x) SOA mass Under low-NO(x) conditions, organic peroxides contribute significantly to the low-NO(x) SOA mass (approximately 61% when SOA forms by nucleation and approximately 25-30% in the presence of seed particles) The contribution of organic peroxides in the SOA decreases with time, indicating photochemical aging Hemiacetal dimers are found to form from C(5) alkene triols and 2-methyltetrols under low-NO(x) conditions; these compounds are also found in aerosol collected from the Amazonian rainforest, demonstrating the atmospheric relevance of these low-NO(x) chamber experiments

The relationship between peak height velocity and physical performance in youth soccer players.

Abstract: Longitudinal changes in height, weight and physical performance were studied in 33 Flemish male youth soccer players from the Ghent Youth Soccer Project. The players' ages at the start of the study...

Inactivation of the p53 pathway in retinoblastoma

Abstract: Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma.