Published Literature Values Research Articles

A systematic review of allometric scaling exponents for IgG mAbs

Increasing complexity of mAbs in development creates challenges in predicting human pharmacokinetic (PK) parameters from preclinical data. The aim of this analysis was to identify optimal allometric scaling exponents. Data were extracted from literature to create a central database (currently the largest available published database) of two-compartment model parameters for mAbs (n = 59) in cynomolgus monkey (CM) and human. Global allometric exponents were calculated and drug-dependent factors were investigated as potential variables in determining the optimal scaling factor. The global exponents for scaling CM mAb PK data were 0.74 (CL), 0.80 (CL with Fc-modified mAbs excluded), 0.44 (CL with Fc-modified mAbs only), 0.71 (Q), 1.12 (V1), and 0.99 (V2). These values are in line with previously published literature values.

Understanding the Magnetic Activity of M Dwarfs: Optical and Near-Infrared Spectroscopic Studies

We present here preliminary results of stellar activities on three active M dwarfs having strong magnetic fields using optical and Near-Infrared (NIR) (0.38 μm − 2.5 μm) spectroscopic observational data using HFOSC on the 2-m HCT and TANSPEC on the 3.6-m DOT. The sample includes new observations of AD Leo, EV Lac, and Stkm2-809 M dwarfs, including published literature values of 89 M dwarfs. To understand the magnetic field activity on those dwarfs, we used the equivalent widths of spectral features Ca IRT triplet (0.850 μm, 0.854 μm, 0.866 μm), which are generally chromospheric and coronal indicators in M dwarfs, and investigate the correlation between those line strengths with Rossby number, which is defined as the ratio of rotation period (Prot) to convective turnover time (τconv). We find a strong correlation between the equivalent widths of Ca IRT b and Ca IRT c and Rossby number (R0). The correlation shows an increasing trend of equivalent widths of those lines with decreasing R0, and saturation of the equivalent widths of those at lower R0 ≤0.1. To estimate R0, we estimate the rotation periods of three observed M dwarfs in our sample from TESS data, and in the case of other M dwarfs, we used the literature values. Interestingly, in TESS light curves of AD Leo, EV Lac, and Stkm2-809 M dwarfs, we find several flare events. We estimated the bolometric flared energy in a range of 1034 to 1037 erg, which is in the superflare range (more than 1032 erg). We estimate the highest flared energy of 1.22 × 1037 erg for EV Lac in TESS sector 57. To produce such kind of high superflare event, we have estimated the required magnetic field strength of 10.53 kG, which will have an impact on the life habitability of planets around such M dwarfs.

A fast Monte Carlo cell-by-cell simulation for radiobiological effects in targeted radionuclide therapy using pre-calculated single-particle track standard DNA damage data.

We developed a new method that drastically speeds up radiobiological Monte Carlo radiation-track-structure (MC-RTS) calculations on a cell-by-cell basis. The technique is based on random sampling and superposition of single-particle track (SPT) standard DNA damage (SDD) files from a "pre-calculated" data library, constructed using the RTS code TOPAS-nBio, with "time stamps" manually added to incorporate dose-rate effects. This time-stamped SDD file can then be input into MEDRAS, a mechanistic kinetic model that calculates various radiation-induced biological endpoints, such as DNA double-strand breaks (DSBs), misrepairs and chromosomal aberrations, and cell death. As a benchmark validation of the approach, we calculated the predicted energy-dependent DSB yield and the ratio of direct-to-total DNA damage, both of which agreed with published in vitro experimental data. We subsequently applied the method to perform a superfast cell-by-cell simulation of an experimental in vitro system consisting of neuroendocrine tumor cells uniformly incubated with 177Lu. The results for residual DSBs, both at 24 and 48 h post-irradiation, are in line with the published literature values. Our work serves as a proof-of-concept demonstration of the feasibility of a cost-effective "in silico clonogenic cell survival assay" for the computational design and development of radiopharmaceuticals and novel radiotherapy treatments more generally.

Drug-drug interactions and dose management of BTK inhibitors when initiating nirmatrelvir/ritonavir (paxlovid) based on physiologically-based pharmacokinetic models

ObjectiveCo-administration of Bruton's tyrosine kinase (BTK) inhibitors with nirmatrelvir/ritonavir is challenging because of potential drug-drug interactions (DDIs). However, clinical trials specifically evaluating such DDIs are absent. To evaluate and quantify the DDIs between them and provide rational dose management strategies of BTK inhibitors, we conducted this study using physiologically-based pharmacokinetic (PBPK) models. MethodsPhysicochemical properties and pharmacokinetic parameters were acquired from the published literature and databases. The PBPK models were developed using Simcyp® software. These models were validated by comparing with published literature values. The successfully validated PBPK models were used to simulate the plasma concentration-time profiles and DDIs in a virtual healthy population receiving BTK inhibitors alone or with ritonavir. ResultsSimulated plasma concentration-time profiles and pharmacokinetic parameters of each drug were in agreement with clinically observed values from literatures. Ritonavir increased ibrutinib maximum plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC) 33- and 53.88-fold, respectively, increased zanubrutinib Cmax and AUC 2.57- and 3.18-fold, respectively, and increased acalabrutinib Cmax and AUC 3.85- and 6.54-fold, respectively. Based on our simulations, dose-adjustment strategies may consist of ibrutinib at 25 mg q48h, zanubrutinib at 80 mg twice-daily and acalabrutinib at 25 mg twice-daily with nirmatrelvir/ritonavir. ConclusionsThe PBPK models predicted the in vivo pharmacokinetics and the DDIs of BTK inhibitors and ritonavir. The prospective simulations not only provided scientific evidence regarding rational dosing management strategies when initiating nirmatrelvir/ritonavir therapy but also provided a reference for the design of clinical DDIs study that may save resources and time. SummaryPaxlovid could increase Cmax and AUC0-τ of BTK inhibitors (ibrutinib, zanubrutinib and acalabrutinib), and dose adjustment strategy of ibrutinib (25 mg q48h), zanubrutinib (80 mg q12h) and acalabrutinib (25 mg q12h) should be considered when combination with nirmatrelvir/ritonavir.

Uncertainty analysis and performance evaluation of thermophysical property measurement of liquid Au in microgravity

A new method for quantifying facility performance has been discussed in this study that encompasses uncertainties associated with thermophysical property measurement. Four key thermophysical properties: density, volumetric thermal expansion coefficient, surface tension, and viscosity of liquid Au have been measured in microgravity environment using two different levitation facilities. Levitation experiments were conducted using the Electrostatic Levitation Furnace (ELF) onboard the ISS in Argon and air, and the TEMPUS Electromagnetic Levitation (EML) facility on a Novespace Zero-G aircraft parabolic flight in Argon. The traditional Maximum Amplitude method was augmented through the use of Frequency Crossover method to identify the natural frequency for oscillations induced on a molten sample during Faraday forcing in ESL. The EML tests were conducted using a pulse excitation method where two techniques, one imaging and one non-imaging, were used to study surface oscillations. The results from both facilities are in excellent agreement with the published literature values. A detailed study of the accuracy and precision of the measured values has also been presented in this work to evaluate facility performance.

Viscosity of methyl and ethyl esters: Experiments and modeling

Viscosity and density have been measured for a number of ethyl esters (ethyl ethanoate, ethyl butanoate, ethyl dodecanoate and ethyl tetradecanoate) at four temperatures between 288.15 and 323.15 K at 101.3 kPa. The measurements are also reported for four of their binary mixtures, over the whole range of compositions, as well as for a single, equimolar ternary and one equimolar, quaternary mixture. The viscosity was measured with a Stabinger viscometer, whilst the density was measured by means of a vibrating U-tube densimeter. The combined expanded uncertainty (k ≈ 2) for the density is 1.7 kg⋅m−3, and relative one for the viscosity is 0.014.The measured viscosity of pure ethyl esters, together with the published literature values, were correlated by means of the extended hard-sphere (EHS) model that has its basis in kinetic theory and the molecular description of the fluid. A separate correlation was developed for methyl esters, based only on the published viscosity values. The correlations, for both families of esters, are valid in the temperature range 283 to 373 K and pressures up to 200 MPa, for all the esters up to and including methyl tetracosanotae and ethyl eicosanoate. The EHS model was used to predict the viscosity of mixture of esters. The measured viscosity data were represented with the average absolute deviation of 2.5% and a maximum deviation of 6.4%.

PSAT087 A de Novo Model for Measuring Long-Term Health Effects of Modified-Release Hydrocortisone Capsules in Adult and Adolescent Patients With Classic Congenital Adrenal Hyperplasia

Abstract Objectives Classic congenital adrenal hyperplasia (C-CAH) is a rare condition caused by enzyme deficiency in cortisol biosynthesis. The condition is characterised by adrenal insufficiency and androgen excess and is associated with numerous disease- and treatment-related comorbidities that impact the length and quality of a patient's life. A de novo model was developed to investigate the long-term health effects of modified-release hydrocortisone capsules (Efmody® / MR-HC) compared to the standard glucocorticoid replacement therapies (including immediate-release hydrocortisone, dexamethasone, and prednisolone) currently used to treat patients with C-CAH. Methods The model is structured as a series of sub-models reflecting key comorbidities in C-CAH: adrenal crisis, cardiovascular disease, bone health, height (adolescents only), obesity, diabetes and infertility. Effects of both disease, i.e. where cortisol and/or androgen levels are too high or low, and the impact of treatment, i.e. physiological or supraphysiological steroid dosing, on each comorbidity are considered where relevant. The model captures accumulating health outcomes from each sub-model and allows quantification of overall impact on health-related quality of life (HRQoL) and mortality. The population is adolescent (>12 years onwards) and adult patients with C-CAH. The intervention is MR-HC, and comparator is standard glucocorticoid replacement therapies currently used in C-CAH. Model inputs, which were composed of MR-HC clinical trial data, published literature values, and clinical opinion, and the modelling approach were validated with seven European clinical experts. The model accumulates the health effect, which is measured as life-years (LYs) and quality-adjusted life years (QALYs), over a lifetime time horizon, from the ages of 12 to 100 years old. Results The model demonstrates that the treatment of C-CAH with standard glucocorticoid replacement therapies known to provide poor hormonal disease control and exposure to supraphysiological steroid dosing long-term have a substantial negative impact on HRQoL and life-expectancy in C-CAH, with modelled outcomes lower than those published for general population. Improved hormonal disease control and physiological steroid dosing with MR-HC compared to standard glucocorticoid replacement therapies result in improvements across the key comorbidities in patients with C-CAH. Quality-adjusted life year (QALY) gains are particularly driven by the reduction in adrenal crises, along with improved growth in the adolescent population and better weight control. Overall, the model demonstrates that long-term treatment of patients with C-CAH with MR-HC, compared to standard glucocorticoid replacement therapies, is expected to extend life by 7.58 years, and results in an additional 3.21 QALYs. Conclusion The model demonstrates that better hormonal disease control without exposing patients to supraphysiological steroid dosing with MR-HC improves key comorbidities in C-CAH resulting in improvement in both the length and the quality of life of patients with C-CAH. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Comments on “Investigation of the inter-ionic interactions of an imidazolium-based ionic liquid with the aqueous solutions of tripotassium citrate and trisodium citrate through volumetric, acoustic and FTIR routes”

A polemic is given concerning the volumetric properties reported for binary aqueous-1-butyl-3-methylimidazolum chloride mixtures in the published paper by Pattanaik and coworkers. The reported limiting values of the apparent molal volumes of 1-butyl-3-methylimidazolium differ significantly from the published literature values of ten independent research groups. Reported limiting values of the apparent molal volumes of trisodium citrate and tripotassium citrate in water were also found to differ significantly from published literature values.

Comments on excess molar volumes reported in “Study of short range and long range molecular interactions in binary liquid mixtures of N,N-dimethylformamide (DMF) and 1-propanol”

• V m E values of Prajapati and coworkers compared to published literature data of ten other researchers. • Published V m E values are much smaller in absolute magnitude than values of Prajapati and coworkers. • Published V m E versus mole fraction curves show simple parabolic behavior. • V m E versus mole fraction curves of Prajapati and coworkers show several local minima and maxima. A polemic is given concerning the volumetric properties reported for binary N,N-dimethylformamide + 1-propanol mixtures in the published paper by Prajapati and coworkers. The reported excess molar volumes differ significantly from the published literature values of ten independent research groups, all of which are much smaller in absolute magnitude than the values reported by Prajapati and coworkers.

Characterization of the AARTFAAC-12 aperture array: radio source counts at 42 and 61 MHz

ABSTRACT Dense aperture arrays provide key benefits in modern astrophysical research. They are flexible, employing cheap receivers, while relying on the ever more sophisticated compute back end to deal with the complexities of signal processing required for optimal use. Their advantage is that they offer very large fields of view and are readily scalable to any size, all other things being equal. Since they represent ‘software telescopes’, the science cases these arrays can be applied to are quite broad. Here, we describe the calibration and performance of the AARTFAAC-12 instrument, which is composed of the twelve centrally located stations of the LOFAR array. We go into the details of the data acquisition and pre-processing, we describe the newly developed calibration pipeline as well as the noise properties of the resulting images and present radio source counts at 41.7 MHz and 61 MHz. We find that AARTFAAC-12 is confusion limited at 0.9 Jy/PSF at 61 MHz with a PSF size of 17 × 11 arcmin and that the normalized source counts agree with the scaled VLSSr and 6C survey counts. The median spectral index of the sources between the two frequencies we observed at is -0.78. Further, we have used the derived source counts to estimate any excess cosmic radio background, and we do not find evidence for it at our observing frequencies compared to published literature values.

Double cantilever beam fracture toughness measurement method for glass

AbstractA simple method of measuring Mode I fracture toughness, KIC, of glass using the double cantilever beam (DCB) geometry is presented. An inert atmosphere is created at the crack tip to prevent subcritical crack growth and enable “pinning” the crack while the specimen is loaded to failure. This was achieved experimentally using liquid toluene or a glovebox with dry argon. KIC values measured by this method showed good agreement with published literature values for selected glasses. Applicability of the analytical stress intensity factor solution based on crack length, crack front curvature, and the height of the crack guiding groove are confirmed through experimental data and finite element analysis. The experimentally observed crack front curvature, which leads near the edges for small groove heights and leads in the center for larger groove heights, is predicted from the geometry of the DCB specimen for a linear elastic solid through finite element modeling.

Pharmacokinetics of 40 kDa Polyethylene glycol (PEG) in mice, rats, cynomolgus monkeys and predicted pharmacokinetics in humans

Conjugation with polyethylene glycol (PEG), PEGylation, has been considered a useful tool to improve drug-like properties of novel small molecules and biologics in drug discovery. PEG40 or 40 kDa PEG is a double-branched PEG, routinely employed to improve the pharmacokinetics (PK) of therapeutics, including successful marketed products such as Pegasys® and Omontys®. However, less is known about the extent of contribution of PEG40 to the overall PK of the PEGylated product. Considering the half-life of PEG40 conjugated PEGylated products ranges from 1 to 14 days in human, this information is immensely valuable. After successfully developing a high sensitivity NMR based analytical method to quantitate PEG40 in mice serum after intravenous (IV) administration (Khandelwal et al., 2019), here, we extend its application to measure PEG40 in serum after IV administration and subcutaneous (SC) absorption in routinely employed non-clinical species in drug discovery, namely, mice, rats and cynomolgus monkeys. We utilized non-compartmental analysis and compartmental modeling to characterize the PK of PEG40 in these non-clinical species. Finally, we employed allometric scaling and Wajima (MRT-Css) method to predict the PK of PEG40 in human after IV administration and SC absorption. In general, our data shows that intrinsic PK parameters of PEG40 in mice, rats and cynomolgus monkeys are in the range of published literature values for PEG40-conjugated products, unless saturable clearance mechanisms are involved. We observed a bioavailability (F) of ~68% in CD-1 mice after SC administration of PEG40. In rats, the clearance (CL) and volume of distribution at steady state (Vss) after IV infusion of PEG40 were 0.079 mL/min/kg and 0.19 L/kg, respectively; and SC bioavailability was ~20%. In cynomolgus monkeys, after IV infusion, CL and Vss of PEG40 were 0.037 mL/min/kg and 0.20 L/kg, respectively; and SC bioavailability was ~69%. In addition, our findings indicate flip-flop kinetics of PEG40 in rodents, but not in cynomolgus monkeys. Finally, in human, intrinsic CL and Vss of PEG40 were projected to be 0.02 mL/min/kg (0.084 L/h) and 0.22 L/kg, respectively. This comprehensive report of PK of PEG40 in non-clinical species and its subsequent prediction in humans is expected to be useful to drug discovery and development scientists for efficient decision-making and optimal resource utilization.

Validation of deterministic code DRAGON5 for the fuel depletion analysis of a PWR pin-cell benchmark

The purpose of this paper is to investigate the DRAGON5 accuracy for studying a PWR pin-cell benchmark, using the ENDF/B-VIII.0 nuclear data library based on 172 energy groups, in DRAGLIB format. This paper focuses on the neutronic and burn-up analysis of the Uranium fuel using DRAGON5 transport code. The precision of the deterministic Code DRAGON5 was validated by comparing Results obtained from analysis of the UO2 pin cell high burn-up benchmark with previously published literature values. The results of a study showed good agreement. Maximum absolute difference in infinite multiplication factor between DRAGON5 and CASMO-4 is found to be 0.23% for UO2 pin cell benchmark. Furthermore, the isotopic inventories and activities have been calculated/evaluated versus the fuel burn-up (BU) time for the natural UO2 fuel, and the enriched UO2 fuel at 1.2%.

Phytochemical Characterization of Native New Mexico Hops

Neomexicanus hops (Humulus lupulus var. neomexicanus) are receiving increased attention within the craft beer and nutraceutical industries. Characterization of bittering acids and essential oils in two neomexicanus varieties revealed wide ranges of bittering acid compositions and distinct essential oil profiles compared with ‘Cascade’ common hops (H. lupulus). Total phenolic content (TPC), expressed as gallic acid equivalent (GAE), in neomexicanus hops ranged from 50 to 100 mg·g−1 GAE, consistently higher than published literature values for hop TPC (2 to 50 mg·g−1 GAE). Results indicate that, compared with ‘Cascade’, neomexicanus hops have unique phytochemical characteristics, which may lead to new applications in brewing and nutraceutical fields.

Comments regarding “Acoustical and physico-chemical study of binary azeotropes (aniline)”

A polemic is given regarding the volumetric data reported in the recent paper by Palaniappan and Nithiyantham. The authors' measured excess molar volumes are found to differ significantly from previously published literature values for four of the six systems studied.

The Bovine Metabolome.

From an animal health perspective, relatively little is known about the typical or healthy ranges of concentrations for many metabolites in bovine biofluids and tissues. Here, we describe the results of a comprehensive, quantitative metabolomic characterization of six bovine biofluids and tissues, including serum, ruminal fluid, liver, Longissimus thoracis (LT) muscle, semimembranosus (SM) muscle, and testis tissues. Using nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography–tandem mass spectrometry (LC–MS/MS), and inductively coupled plasma–mass spectrometry (ICP–MS), we were able to identify and quantify more than 145 metabolites in each of these biofluids/tissues. Combining these results with previous work done by our team on other bovine biofluids, as well as previously published literature values for other bovine tissues and biofluids, we were able to generate quantitative reference concentration data for 2100 unique metabolites across five different bovine biofluids and seven different tissues. These experimental data were combined with computer-aided, genome-scale metabolite inference techniques to add another 48,628 unique metabolites that are biochemically expected to be in bovine tissues or biofluids. Altogether, 51,801 unique metabolites were identified in this study. Detailed information on these 51,801 unique metabolites has been placed in a publicly available database called the Bovine Metabolome Database.

Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials.

To characterize hydroxychloroquine (HCQ) exposure in patients with rheumatic disease receiving longterm HCQ compared to target concentrations with reported antiviral activity against the coronavirus disease 2019 caused by SARS-CoV-2 (COVID-19). We evaluated total HCQ concentrations in serum and plasma from published literature values, frozen serum samples from a pediatric systemic lupus erythematosus trial, and simulated concentrations using a published pharmacokinetic model during pregnancy. For each source, we compared observed or predicted HCQ concentrations to target concentrations with reported antiviral activity against SARS-CoV-2. The average total serum/plasma HCQ concentrations were below the lowest SARS-CoV-2 target of 0.48 mg/l in all studies. Assuming the highest antiviral target exposure (total plasma concentration of 4.1 mg/l), all studies had about one-tenth the necessary concentration for in vitro viral inhibition. Pharmacokinetic model simulations confirmed that pregnant adults receiving common dosing for rheumatic diseases did not achieve target exposures; however, the models predict that a dosage of 600 mg once a day during pregnancy would obtain the lowest median target exposure for most patients after the first dose. We found that the average patient receiving treatment with HCQ for rheumatic diseases, including children and non-pregnant/pregnant adults, are unlikely to achieve total serum or plasma concentrations shown to inhibit SARS-CoV-2 in vitro. Nevertheless, patients receiving HCQ long term may have tissue concentrations far exceeding that of serum/plasma. Because the therapeutic window for HCQ in the setting of SARS-CoV-2 is unknown, well-designed clinical trials that include patients with rheumatic disease are urgently needed to characterize the efficacy, safety, and target exposures for HCQ.

Determining the surface magnetic field strength of neutron stars using x-ray observations

This paper introduces the physics surrounding accretion onto a magnetised neutron star in a binary system. It focuses on the use of experimentally observed cyclotron spectral features to estimate the surface magnetic field strength of the neutron star. A semi-classical description of the cyclotron spectral lines is given, allowing the magnetic field close to the surface of the neutron star to be estimated without recourse to sophisticated quantum mechanics. The estimated values are compared to published literature values for a selection of five accreting binary systems and shown to agree to within 13%. The limitations of the semi-classical approach are also discussed. The work presented here is accessible to undergraduate university students and is suitable for inclusion into introductory undergraduate courses on the subject.

Volcanic conduit controls on effusive-explosive transitions and the 2010 eruption of Merapi Volcano (Indonesia)

Individual volcanoes can produce both effusive and explosive eruptions. A transition between these two eruption styles dramatically changes the hazards and can occur either between distinct eruption events or within one eruption episode. The causes of these transitions are difficult to determine due to the number of system parameters that can influence whether or not magma fragments in a runaway process. We apply a numerical model of magma ascent in a volcanic conduit to isolate and test the effects of key parameters related to magma rheology and system geometry. We find that for a given volcanic system, parameters that control magma viscosity, such as initial water mass fraction, initial crystal volume fraction, and temperature, have the greatest influence on whether or not magma fragments during ascent and erupts explosively. We also define a ‘critical condition’ for the full set of initial parameters under which a transition in eruption style, from effusive to explosive or the reverse, is more likely to occur. Under these conditions, small heterogeneities in the water or crystal content of the magma, or small perturbations to the conduit pressure gradient due to magma chamber overpressure or dome growth or collapse, can disrupt the magmatic conditions and cause a transition in eruption style. The 2010 VEI 4 eruption of Merapi Volcano included both effusive and explosive phases and was larger by an order of magnitude than its eruptions during the previous century. We constrain our model for the Merapi system using published literature values and show that between the previous eruption in 2006 and the 2010 eruption, the shallow magmatic system at Merapi reached critical conditions due to the ascent from depth of a large, hotter, more volatile-rich magma. Under these critical conditions and according to our model results, small changes in the volatile content of the magma, small dome collapses, subtle changes in degassing rate, or the addition of CO2 to the magma through decarbonation of the bedrock, are all feasible mechanisms for triggering rapid transitions between effusive and explosive activity during the 2010 eruption period.

Analysis of the H.E.S.S. public data release with ctools

The ctools open-source software package was developed for the scientific analysis of astronomical data from Imaging Air Cherenkov Telescopes (IACTs), such as H.E.S.S., VERITAS, MAGIC, and the future Cherenkov Telescope Array (CTA). To date, the software has been mainly tested using simulated CTA data; however, upon the public release of a small set of H.E.S.S. observations of the Crab nebula, MSH 15–52, RX J1713.7–3946, and PKS 2155–304 validation using real data is now possible. We analysed the data of the H.E.S.S. public data release using ctools version 1.6 and compared our results to those published by the H.E.S.S. Collaboration for the respective sources. We developed a parametric background model that satisfactorily describes the expected background rate as a function of reconstructed energy and direction for each observation. We used that model, and tested all analysis methods that are supported by ctools, including novel unbinned and joint or stacked binned analyses of the measured event energies and reconstructed directions, and classical On-Off analysis methods that are comparable to those used by the H.E.S.S. Collaboration. For all analysis methods, we found a good agreement between the ctools results and the H.E.S.S. Collaboration publications considering that they are not always directly comparable due to differences in the datatsets and event processing software. We also performed a joint analysis of H.E.S.S. and Fermi-LAT data of the Crab nebula, illustrating the multi-wavelength capacity of ctools. The joint Crab nebula spectrum is compatible with published literature values within the systematic uncertainties. We conclude that the ctools software is mature for the analysis of data from existing IACTs, as well as from the upcoming CTA.