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11.
Hendrik Koffijberg Koen Degeling Maarten J. IJzerman Veerle M.H. Coupé Marjolein J.E. Greuter 《Value in health》2021,24(2):206-215
ObjectivesMetamodeling can address computational challenges within decision-analytic modeling studies evaluating many strategies. This article illustrates the value of metamodeling for evaluating colorectal cancer screening strategies while accounting for colonoscopy capacity constraints.MethodsIn a traditional approach, the best screening strategy was identified from a limited subset of strategies evaluated with the validated Adenoma and Serrated pathway to Colorectal CAncer model. In a metamodeling approach, metamodels were fitted to this limited subset to evaluate all potentially plausible strategies and determine the best overall screening strategy. Approaches were compared based on the best screening strategy in life-years gained compared with no screening. Metamodel runtime and accuracy was assessed.ResultsThe metamodeling approach evaluated >40 000 strategies in <1 minute with high accuracy after 1 adaptive sampling step (mean absolute error: 0.0002 life-years) using 300 samples in total (generation time: 8 days). Findings indicated that health outcomes could be improved without requiring additional colonoscopy capacity. Obtaining similar insights using the traditional approach could require at least 1000 samples (generation time: 28 days). Suggested benefits from screening at ages <40 years require adequate validation of the underlying Adenoma and Serrated pathway to Colorectal CAncer model before making policy recommendations.ConclusionsMetamodeling allows rapid assessment of a vast set of strategies, which may lead to identification of more favorable strategies compared to a traditional approach. Nevertheless, metamodel validation and identifying extrapolation beyond the support of the original decision-analytic model are critical to the interpretation of results. The screening strategies identified with metamodeling support ongoing discussions on decreasing the starting age of colorectal cancer screening. 相似文献
12.
Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation. 总被引:2,自引:0,他引:2
Hisataka Kobayashi Koen Reijnders Sean English Alexander T Yordanov Diane E Milenic Anastasia L Sowers Deborah Citrin Murali C Krishna Thomas A Waldmann James B Mitchell Martin W Brechbiel 《Clinical cancer research》2004,10(22):7712-7720
Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies. 相似文献
13.
Anne Smets Koen Mortelé Nathalie De Wever Yves Benoit Marleen Praet Marc Kunnen 《Pediatric radiology》1998,28(5):329-331
We report a 3-year, 5-month-old boy with an adrenocortical carcinoma. These tumours are rare and highly malignant in childhood.
In most cases they are functional, secreting adrenocortical hormones. In this case there was a misleading coexistence with
a second abdominal neoplasm, which was a ganglioneuroma; this is a rare benign tumour arising from the sympathetic nervous
system. The imaging investigations and their findings are discussed and correlated with pathology.
Received: 15 January 1997 Accepted: 15 October 1997 相似文献
14.
Ulrich Hegerl Roland Mergl Christian Sander Jens Dietzel Istvan Bitter Koen Demyttenaere Ricardo Gusmão Ana González-Pinto Iñaki Zorrilla Adriana García Alocén Victor Perez Sola Eduard Vieta Georg Juckel Ulrich S. Zimmermann Michael Bauer Pascal Sienaert Sónia Quintão Marc-Andreas Edel Michael Kluge 《European neuropsychopharmacology》2018,28(1):185-194
Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605). 相似文献
15.
16.
Crowding occurs when surrounding objects (flankers) impair target perception. A key property of crowding is the weaker interference when target and flankers strongly differ on a given dimension. For instance, identification of a target letter is usually superior with flankers of opposite versus the same contrast polarity as the target (the “polarity advantage”). High performance when target-flanker similarity is low has been attributed to the ungrouping of target and flankers. Here, we show that configural cues can override the usual advantage of low target-flanker similarity, and strong target-flanker grouping can reduce – instead of exacerbate – crowding. In Experiment 1, observers were presented with line triplets in the periphery and reported the tilt (left or right) of the central line. Target and flankers had the same (uniform condition) or opposite contrast polarity (alternating condition). Flanker configurations were either upright (||), unidirectionally tilted (\\ or //), or bidirectionally tilted (\/ or /\). Upright flankers yielded stronger crowding than unidirectional flankers, and weaker crowding than bidirectional flankers. Importantly, our results revealed a clear interaction between contrast polarity and flanker configuration. Triplets with upright and bidirectional flankers, but not unidirectional flankers, showed the polarity advantage. In Experiments 2 and 3, we showed that emergent features and redundancy masking (i.e. the reduction of the number of perceived items in repeating configurations) made it easier to discriminate between uniform triplets when flanker tilts were unidirectional (but not when bidirectional). We propose that the spatial configurations of uniform triplets with unidirectional flankers provided sufficient task-relevant information to enable a similar performance as with alternating triplets: strong-target flanker grouping alleviated crowding. We suggest that features which modulate crowding strength can interact non-additively, limiting the validity of typical crowding rules to contexts where only single, independent dimensions determine the effects of target-flanker similarity. 相似文献
17.
ABSTRACT: BACKGROUND: The purpose of this correspondence article is to report opinion amongst experts in the delirium field as to why, despite on-going training for all health professionals, delirium continues to be under recognised. Consensus was obtained by means of two conference workshops and an online survey of members of the European Delirium Association.Major barriers to recognition at an individual level include ignorance about the benefit of treating delirium. At an organisational level, reflecting socio-cultural attitudes, barriers include a low strategic and financial priority and the fact that delirium is an orphan condition falling between specialties. 相似文献
18.
G. Tournel C. Cauffiez J. Leclerc I. Billaut-Laden D. Allorge D. Chevalier 《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(12):1433-1438
Since human cytochrome P450 2F1 (CYP2F1) is predominantly expressed in lung tissue and is involved in the metabolism of various pneumotoxicants with potential carcinogenic effects, variations in the nucleotidic sequence of its gene may contribute to interindividual and interethnic differences in the susceptibility to lung tumorigenesis. The aim of the current study was to compare the frequency of a previously reported frameshift mutation, namely c.14_15insC, responsible for the synthesis of a severely truncated protein, between several populations of different ethnic origins. The frequencies of this polymorphism were 26.1, 51.6, 42.7 and 22.9% in French, Gabonese, Senegalese, and Tunisian population samples, respectively, thereby representing a substantial inter ethnic variation in the CYP2F1 gene. These findings provide data for further studies that investigate the potential association of CYP2F1 haplotypes with an incidence of lung cancer genesis in respect of ethnicity. 相似文献
19.
LDL receptor cooperates with LDL receptor-related protein in regulating plasma levels of coagulation factor VIII in vivo 总被引:5,自引:1,他引:5 下载免费PDF全文
Low-density lipoprotein (LDL) receptor (LDLR) and LDLR-related protein (LRP) are members of the LDLR family of endocytic receptors. LRP recognizes a wide spectrum of structurally and functionally unrelated ligands, including coagulation factor VIII (FVIII). In contrast, the ligand specificity of LDLR is restricted to apolipoproteins E and B-100. Ligand binding to the LDLR family is inhibited by receptor-associated protein (RAP). We have previously reported that, apart from LRP, other RAP-sensitive mechanisms contribute to the regulation of FVIII in vivo. In the present study, we showed that the extracellular ligand-binding domain of LDLR interacts with FVIII in vitro and that binding was inhibited by RAP. The physiologic relevance of the FVIII-LDLR interaction was addressed using mouse models of LDLR or hepatic LRP deficiency. In the absence of hepatic LRP, LDLR played a dominant role in the regulation and clearance of FVIII in vivo. Furthermore, FVIII clearance was accelerated after adenovirus-mediated gene transfer of LDLR. The role of LDLR in FVIII catabolism was not secondary to increased plasma lipoproteins or to changes in lipoprotein profiles. We propose that LDLR acts in concert with LRP in regulating plasma levels of FVIII in vivo. This represents a previously unrecognized link between LDLR and hemostasis. 相似文献
20.
Koen Hogenelst Robert A. Schoevers Marije aan het Rot 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(8)