Pharmacokinetic–pharmacodynamic modeling of maintenance therapy for childhood acute lymphoblastic leukemia DOI Creative Commons

Anna Gebhard,

Patrick Lilienthal,

Markus Metzler

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 20, 2023

Abstract In the treatment of childhood acute lymphoblastic leukemia (ALL), current protocols combine initial high-dose multiagent chemotherapy with prolonged oral therapy 6-mercaptopurine (6MP) and low-dose methotrexate (MTX) maintenance therapy. Decades research on ALL have resulted in survival rates approximately 90%. However, dose-response relationships vary widely between patients insight into influencing factors, that would allow for improved personalized management, is insufficient. We use a detailed data set measurements thioguanine nucleotides MTX red blood cells absolute neutrophil count (ANC) to develop pharmacokinetic models 6MP MTX, as well pharmacokinetic–pharmacodynamic (PKPD) model capable predicting individual ANC levels thus contributing development strategies. Here, we show integrating metabolite full PKPD improves results when less available, but predictions are comparable those fixed availability not limited, providing further evidence quality existing models. With this comprehensive leading dynamics similar simpler models, validate suitability structure provide foundation exploration strategies through simulation optimization.

Language: Английский

Models with higher effective dimensions tend to produce more uncertain estimates DOI Creative Commons
Arnald Puy,

Pierfrancesco Beneventano,

Simon A. Levin

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(42)

Published: Oct. 19, 2022

Mathematical models are getting increasingly detailed to better predict phenomena or gain more accurate insights into the dynamics of a system interest, even when there no validation training data available. Here, we show through ANOVA and statistical theory that this practice promotes fuzzier estimates because it generally increases model's effective dimensions, i.e., number influential parameters weight high-order interactions. By tracking evolution dimensions output uncertainty at each model upgrade stage, modelers can ponder whether addition detail truly matches purpose quality fed it.

Language: Английский

Citations

46
Parton distributions need representative sampling DOI Creative Commons
Aurore Courtoy, J. Huston, Pavel Nadolsky

et al.

Physical review. D/Physical review. D., Journal Year: 2023, Volume and Issue: 107(3)

Published: Feb. 10, 2023

In global QCD fits of parton distribution functions (PDFs), a large part the estimated uncertainty on PDFs originates from choices parametric functional forms and fitting methodology. We argue that these types uncertainties can be underestimated with common PDF ensembles in high-stake measurements at Large Hadron Collider Tevatron. A fruitful approach to quantify is view them as arising sampling allowed solutions multidimensional space. This applies powerful insights gained recent statistical studies large-scale population surveys quasi-Monte Carlo integration methods. particular, may affected by big data paradox, which stipulates more experimental do not automatically raise accuracy PDFs---close attention quality possible essential. To test if an observable truly representative all acceptable solutions, we introduce technique (``a hopscotch scan'') based combination parameter scans stochastic sampling. With this technique, examine key LHC cross sections 13 TeV obtained public NNPDF4.0 code, while accounting for likelihood distribution. show charm momentum fraction $x$ gluon small are enlarged. analytic minimization (Hessian) formalism, tolerance must sufficiently complete experiments.

Language: Английский

Citations

21
Uncovering heterogeneous effects in computational models for sustainable decision-making DOI Creative Commons
Mariia Kozlova, Robert J. Moss, Julian Scott Yeomans

et al.

Environmental Modelling & Software, Journal Year: 2023, Volume and Issue: 171, P. 105898 - 105898

Published: Nov. 24, 2023

Computational modeling is frequently incorporated into environmental decision-making in order to capture inherently complex relationships and system dynamics. The complexity of such models often lies various heterogeneous effects that arise due the interaction different input factors or designed structural variation model. In past, sensitivity analysis approaches have been implemented attempts identify essential decision factors. However, existing methods fail critical information presence effects. this paper, recently introduced simulation decomposition (SimDec) visualization method extended include quantitative analysis. framework tested on several problems shown behavior. A formal definition classification for computational introduced. open-sourced a variety scientific programming languages.

Language: Английский

Citations

18
Unpacking the modelling process via sensitivity auditing DOI Creative Commons
Samuele Lo Piano, Razi Sheikholeslami, Arnald Puy

et al.

Futures, Journal Year: 2022, Volume and Issue: 144, P. 103041 - 103041

Published: Sept. 29, 2022

Acknowledging the conditionality of model-based evidence facilitates dialogue between model developers and users, especially when models are used to guide decisions at science-policy interface. In general, users have limited access verify realism a model, being only exposed plausibility trustworthiness; instead, modellers an array validation verification techniques available. end, credibility is what both aim for, also in interest shielding from possible pitfall over-interpreting results. To this contribution we discuss sensitivity auditing, extension analysis, that can help overcome communication barriers foster around modelling activities. The use auditing not restricted sense, but it be applied any policy-relevant instance quantification, including metrics, rankings indicators. We present six real-world applications instances quantification range socio-environmental systems, public health, education, water-food nexus. These examples reveal usefulness facilitating proper numbers science-policy-society interface avoiding uncertainty laundering.

Language: Английский

Citations

27
Andean headwater and piedmont streams are hot spots of carbon dioxide and methane emissions in the Amazon basin DOI Creative Commons
Gonzalo Chiriboga, Alberto Borges

Communications Earth & Environment, Journal Year: 2023, Volume and Issue: 4(1)

Published: March 16, 2023

Abstract Rivers substantially contribute to global greenhouse gas emissions, yet emissions from headwater streams are poorly constrained. Here, we report dissolved concentrations of carbon dioxide (CO 2 ), methane (CH 4 and nitrous oxide (N O) in Andean piedmont the Napo River basin Ecuador, part Amazon catchment. Concentrations increased exponentially with elevation decrease between 3990 175 m above sea level. Concentration changes scaled catchment slope, were attributed variations transfer velocity, forest cover, inundation extent, water temperature. We estimate river across whole using existing data for lowland Central Amazon. find that mountainous hotspots CO CH emission, respective areal fluxes being 1.7 4.5 higher streams, 1.2 6.6 than streams. Together, rivers represented 35% 72% scale integrated fluvial diffusive emissions. Conversely, N O low compared

Language: Английский

Citations

16
Effects of sample size, data quality, and species response in environmental space on modeling species distributions DOI
Lifei Wang, Donald A. Jackson

Landscape Ecology, Journal Year: 2023, Volume and Issue: 38(12), P. 4009 - 4031

Published: Oct. 6, 2023

Language: Английский

Citations

14
Climate change impact on sub-tropical lakes – Lake Kinneret as a case study DOI
Shajar Regev, Yohay Carmel, Dirk Schlabing

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 921, P. 171163 - 171163

Published: Feb. 23, 2024

Language: Английский

Citations

5
Using high level validation to increase lake ecosystem model reliability DOI
Shajar Regev, Yohay Carmel, Gideon Gal

et al.

Environmental Modelling & Software, Journal Year: 2023, Volume and Issue: 162, P. 105637 - 105637

Published: Feb. 1, 2023

Language: Английский

Citations

12
Impact assessment culture in the European Union. Time for something new? DOI Creative Commons
Andrea Saltelli, Marta Kuc‐Czarnecka, Samuele Lo Piano

et al.

Environmental Science & Policy, Journal Year: 2023, Volume and Issue: 142, P. 99 - 111

Published: Feb. 16, 2023

Current approaches and cultures for the economic evaluations of environmental health policies may suffer from excessive reliance on a standard neoclassic toolbox that neglects alternative perspectives. This prematurely limit spectrum available policy options. Here we show how inclusion neglected currents thought such as non-Ricardian economics, bioeconomics set qualitative-quantitative methods post-normal science leads to richer perspectives more inclusive uses quantitative evidence, opens analysis possible futures. We also present some case studies in energy, water, climate domains highlight point practical context policy-oriented audience. situate our recent calls EU social sciences humanities assessment works.

Language: Английский

Citations

12
Mathematical models: a state of exception DOI Creative Commons
Andrea Saltelli, Arnald Puy, Monica Di Fiore

et al.

International Review of Applied Economics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 18

Published: June 11, 2024

Models live in a state of exception. Their versatility, the variety their methods, impossibility falsification and epistemic authority allow mathematical models to escape, better than other cases quantification, lenses sociology humanistic disciplines. This endows with pretence neutrality that perpetuates asymmetry between developers users. are thus both underexplored overinterpreted. While retaining firm grip on policy, they reinforce entrenched culture transforming political issues into technical ones, possibly decreasing citizens' agency favouring anti-democratic policies. To combat this exception, one should question reproducibility models, foster complexity interpretation rather construction, encourage forms activism aimed at achieving reciprocal domestication society. breach solitude modellers, more actors engage practices such as assumption hunting, modelling process, sensitivity analysis auditing.

Language: Английский

Citations

4