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Background Pharmacogenetics (PGx), especially in regard to CYP2D6, is gaining more importance in routine clinical settings. Including phenoconversion effects (PC) in result interpretation could maximize its potential benefits. However, studies on genetics of pharmacokinetic genes including the functional enzyme status are lacking. Aim The retrospective analyses of clinical routine data aimed to investigating how the CYP2D6 functional enzyme status affects serum concentrations and metabolite-to-parent ratios of seven common psychotropic drugs and allows an evaluation of the relevance of this information for patient care. Method Two patient cohorts (total n = 316; 44.2 ± 15.4 years) were investigated for the CYP2D6 functional enzyme status and its associations with drug exposure and metabolism of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone and quetiapine. Results We found an increase in intermediate and poor metabolizers, as well as a decrease in normal metabolizers of CYP2D6 when including PC. Moreover, we found associations between amitriptyline exposure with the phenoconversion-corrected activity score of CYP2D6 (Spearman correlation; p = 0.03), and risperidone exposure with CYP2D6 functional enzyme status (Kruskal–Wallis test; p = 0.01), as well as between metabolite-to-parent ratio of venlafaxine and risperidone with CYP2D6 functional enzyme status (Kruskal–Wallis test; p p = 0.05). Conclusion The data stress the relevance of PC-informed PGx in psychopharmacological treatment and suggest that PC should be included in PGx result interpretation when PGx is implemented in routine clinical care, especially before initiating amitriptyline- or risperidone-treatment, to start with a dose adequate to the respective CYP2D6 functional enzyme status. Moreover, PGx and therapeutic drug monitoring should be used complementary but not alternatively.

Figure 2 of the original article contained an error in the location of some of the radiocarbon dates in Cores 1 and 2. This does not change the main findings of the paper. The corrected figure is below.

Zusammenfassung Ziel der Studie Die FACT-PGx Studie sollte Barrieren bei der Implementierung von pharmakogenetischen Testungen auf Station einer psychiatrischen Klinik aufdecken, um sie in Folge überwinden zu können, so dass die flächendeckende Implementierung schneller erfolgen kann. Methodik 104 Patienten (50% Frauen) mit F32.x oder F33.x wurden genotypisiert. 67 Patienten (64%; 57% Frauen) beantworteten den selbstentwickelten Fragebogen. Der Einfluss demografischer Daten wie Bildungsstand, Alter und Vorbehandlungen die Antworten des Fragebogens wurden mittels t-Test (kategorial) Wilcoxon-Rank-Test (kontinuierlich) untersucht. Ergebnisse Kein Patient lehnte eine Genotypisierung ab. 99% glaubten, dass PGx ihren Aufenthalt verkürzen könne. Patienten >40 Jahre und mit höherem Bildungsgrad waren eher bereit, Geld für eine Genotypisierung auszugeben (beides p=0.009). Durchschnittlich waren die Patienten bereit, im Mittel 117,42 € +/- 140,49 € auszugeben und 15,83+/- 8,92 Tage auf Befunde zu warten. Die Prozessabläufe für eine Genotypisierung in der Klinik unterscheiden sich von dem Routinelabor. Schlussfolgerung Patienten stellen bei der Implementierung keine Barriere dar, sondern befördern eher die Implementierung. Prozessabläufe können Barrieren darstellen, die jedoch durch Optimierung überwunden werden können.

This study contributes to the call for influencing practice by increasing attention to how learning environments can be designed to support learning in statistical inference. We report on a design experiment in secondary school (students 14–16 years old), that resulted in a set of lessons with the learning goal of teaching students how to apply concepts and principles of hypothesis testing for making an inference as to whether or not students in secondary school can taste the difference between two brands of cola soda. The design experiment resulted in four design principles for a simulation-based approach for learning hypothesis testing in secondary school. The design principles highlight the combination of practical and digital simulations of samplings. They stress the need for using random generators that allow for high reliability in collecting sample data and introduce a simulation-based method for determining p-values, i.e. to quantify how likely or surprising a sample result, or a result more extreme, is under a null hypothesis.

The purpose of this study is to further our understanding of orchestrating math-talk with digital technology. The technology used is common in Swedish mathematics classrooms and involves personal computers, a projector directed towards a whiteboard at the front of the class and software programs for facilitating communication and collective exploration. We use the construct of instrumental orchestration to conceptualize a teacher’s intentional and systematic organization and use of digital technology to guide math-talk in terms of a collective instrumental genesis. We consider math-talk as a matter of inferential reasoning, taking place in the Game of Giving and Asking for Reasons (GoGAR).The combination of instrumental orchestration and inferential reasoning laid the foundation of a design experiment that addressed the research question: How can collective inferential reasoning be orchestrated in a technology-enhanced learning environment? The design experiment was conducted in lower-secondary school (students 14–16 years old) and consisted of three lessons on pattern generalization. Each lesson was tested and refined twice by the research team. The design experiment resulted in the emergence of the FlexTech orchestration, which provided teachers and students with opportunities to utilize the flexibility to construct, switch and mark in the orchestration of an instrumental math-GoGAR.

Summary Understanding the cement hardening process and determining the development of the state of stress in the cement under specific downhole conditions are challenging but fundamental requirements to perform an accurate prediction of wellbore integrity. As an essential component of the state of stress, the temporal variation of cement pore pressure is a critical factor that affects the occurrence of cement failure. In this study, we present a novel laboratory setup to measure the cement pore pressure variation during hardening under representative downhole conditions, including the pressure, temperature, and water exchange between the cement and formation. The pore pressure measurements are further incorporated with a staged finite element analysis (FEA) approach to investigate the state of stress development during cement hardening and to evaluate cement failure under different operations and after different wait-on-cement (WOC) periods. The laboratory measurements show that the external water supply from the formation significantly impedes the pore pressure drop in the cement. The numerical results indicate that the accelerated pore pressure decrease obtained without considering downhole conditions elevates the contact pressure at the cement-formation interfaces significantly and moderately increases the von Mises stress in the cement. The numerical results further predict that the accelerated pore pressure decrease leads to an overestimation of shear failure during pressure testing and steamflooding operations but an underestimation of debonding failure during severe fluid loss and injection-related cooling processes. Based on the results of the integrated laboratory and numerical approach, qualitative and quantitative suggestions are provided for field operations to inhibit wellbore integrity risk during the wellbore life cycle.

We analyzed sediment cores from coastal Lake Izabal, Guatemala, to infer Holocene biogeochemical changes in the lake. At ca. 8370 calibrated yr B.P. (cal. yr B.P.), marine waters entered the lake, which presently lies ~38 km from the Caribbean coast. Temporal correlation between Early Holocene drainage of high-latitude Lakes Agassiz and Ojibway (in North America) and marine flooding of Lake Izabal suggests a causal link between the two processes. Our data indicate a relative sea-level jump of 2.60 ± 0.88 m, which is larger than previous estimates of sea-level rise during the 8.2 ka event. The inferred sea-level jump, however, cannot be explained solely by the volume of water released during drainage of Lakes Agassiz and Ojibway. Instead, we propose that previous studies underestimated the magnitude of Lakes Agassiz and Ojibway discharge, or that additional meltwater sources contributed to global sea-level rise at that time.

Die Innovationskraft von Forschungsleistungen wird oft an Inputs wie Forschungsmitteln oder Outputs wie Patentanmeldungen gemessen. Hier wird ein neuartiger Indikator für pharmazeutische Innovationskraft vorgestellt, der sich auf die weltweiten medizinischen Durchbrüche und die assoziierten Patente konzentriert. Demnach sind US-Unternehmen von 2010 bis 2019 für 55 % der weltweiten medizinischen Durchbrüche verantwortlich, ihre deutschen Konkurrenten für rund 9 %. Bei den zugrundeliegenden Ankerpatenten ist die Dominanz der USA mit 62 % noch größer - aus Deutschland kommen nur 7 % der Ankerpatente. US-Universitäten halten 3,8 % aller Ankerpatente - deutsche Universitäten keine. Die Schwäche der deutschen Universitäten kann nicht durch die deutschen außeruniversitären Forschungsinstitute ausgeglichen werden. The innovative strength of research performance is often measured in terms of inputs such as research funds or outputs such as patent applications. We present a novel indicator of pharmaceutical innovativeness that focuses on global medical breakthroughs and associated patents. According to this indicator, US companies account for 55 % of global medical breakthroughs from 2010 to 2019, and their German competitors account for about 9 %. In terms of underlying anchor patents, the dominance of the US is even larger, at 62 %, while only 7 % of anchor patents come from Germany. US universities hold 3.8 % of all anchor patents; German universities hold none. The weakness of German universities cannot be compensated by German non-university research institutes.

Cet article part de l’observation que la « question du travail », presque disparue des etudes africaines depuis les annees 1980, est de retour. La renaissance actuelle de cette thematique, liee a l’interet profond suscite par le travail informel et precaire, va de pair avec la consideration d’une grande variete de formes de travail, depuis celui des femmes qui executent des tâches domestiques jusqu’aux activites de contrebande. Il s’agit, dans cet essai, de reflechir sur l’etat de la recherche sur le travail et les travailleurs en Afrique, en se basant sur les evolutions majeures qui ont marque les relations et les pratiques de travail depuis la decolonisation.

ABSTRACT: Wellbore integrity to ensure efficient, economical, and environmentally friendly operations is a significant and fundamental challenge for CO2 sequestration wells. The carbonation reaction between Portland cement and CO2 can change the microstructure of the cement skeleton, change the cement mechanical properties, damage the annular seal, and finally induce CO2 leakage. This study utilizes an integrated approach including a CO2-cement degradation test, mechanical tests for strength and elastic properties, X-Ray Fluorescence (XRF) and X-Ray Diffraction (XRD) for composition analysis, and finite element analysis for failure evaluation. The mechanical test results show that the carbonation reaction can improve the sealing effect of the cement during the early stage of degradation (~2 weeks). Mechanical and geochemistry test results show that the carbonation reaction would fundamentally change the composition and microstructure of the cement matrix after long-term CO2 degradation, thereby inducing significant decreases in strength, and enhanced porosity, and permeability. The numerical results indicate that during long-term CO2 injection, the sealing effect of the cement would decrease gradually, and the cement sheath is more likely to fail under external loads arising from wellbore pressure and temperature variations. The mechanical and geochemical test results also show that the temporal variations of cement strength and Ca2+ composition have a strong similarity, which should be further analyzed for possible correlation. In summary, this study provides an integrated approach to qualitatively and quantitatively evaluate the cement degradation and predict failure of CO2 sequestration wells. The allowable wellbore pressure and temperature ranges can be provided for different degrees of cement sheath degradation to assist the field operations and cement slurry design of CO2 sequestration wells. 1. INTRODUCTION The unwanted leakage from the CO2-injection wells impedes the stable and economic industrialization of the CO2 geological sequestration. Therefore, maintaining wellbore integrity becomes a priority task to ensure a successful CO2 sequestration project (Zhang et al. 2019, Xu et al. 2022). For CO2-injection wells, the carbonation reaction between Portland cement and CO2 is a complicated process controlled by CO2 concentration, presence of water, age of the cement, pressure, temperature, and the level of intactness of the cement matrix (Zhang et al. 2021, 2022a). Oilwell cement and CO2 reaction have been extensively investigated by various laboratory studies, including the influence of pressure and temperature (Barlet-Gouedard et al. 2006; Omosebi et al. 2017), reaction period (Barlet-Gouedard et al. 2006), and presence of various additives (Barlet-Gouedard et al. 2006). The major chemical reactions between CO2 and different compositions in the cement are presented in Figure 1 and Equation 1 to 5 (Kashef-Haghighi et al. 2015).

ABSTRACT: Conducting safe and effective waste disposal and sequestration processes relies on an accurate determination of the reservoir extent and the prevailing boundary conditions. Due to the limitations surrounding the acquisition and analysis of the reservoir geometry, waste disposal, cuttings re-injection, and CO2 sequestration studies are based on simplifying assumptions regarding the lateral and vertical fluid flow boundary conditions. These assumptions can jeopardize the study’s outcomes, especially for green fields. Common boundary conditions considered are limited to either open (steady-state) or closed (semi-steady state) lateral boundaries, alongside a complete or partially sealing caprock. This study uses pressure transient analysis to provide a quantitative tool to assess a wider variety of fluid flow boundary conditions. We show that a short drawdown followed by a pro-longed buildup test can identify the fluid flow boundary condition, including closed, open, semi-open, and infinite systems. The significant difference in CO2 storage capacity and the different geomechanical risks associated with various fluid flow boundary conditions suggest that the presented methodology should be considered prior to fluid injection scenarios. 1 INTRODUCTION Geologic sequestration is an increasingly important strategy to dispose of drilling fluids, saltwater, and hazardous waste and to reduce the CO2 concentration in the atmosphere (Mortezaei et al., 2021). The most viable CO2 sequestration targets include deep saline aquifers and mature hydrocarbon fields (Garcia et al., 2010; Sarhosis et al., 2018; Bachu, 2003; Holloway, 2001; Holloway and Savage, 1993; Klara et al., 2003). The fluid flow boundary conditions of the target storage medium need to be known to predict the target formation’s storage capacity, the spreading of the injected plume, and the geomechanical risks associated with the pore pressure increase. The current practices commonly consider an assortment of simplified boundary conditions that include open and closed boundaries when it comes to sequestration.

Sandro Salamone,1 Sara Spirito,2 Maurizio Simmaco,2 Marius Unger,1 Saskia Preissner,3 Björn-Oliver Gohlke,1 Andreas Eckert,1 Robert Preissner1 1Science-IT and Institute of Physiology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany; 2Department of Neurosciences, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University and Laboratory of Clinical Biochemistry, Sant’Andrea Hospital, Rome, Italy; 3Department Oral and Maxillofacial Surgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, GermanyCorrespondence: Robert Preissner, Science-IT and Institute of Physiology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Philippstr. 12, Berlin, 10115, Germany, Tel +49 30 450 655 208, Fax +49 30 450 655 300, Email robert.preissner@charite.dePurpose: Pharmacogenetic counselling is a complex task and requires the efforts of an interdisciplinary team, which cannot be implemented in most cases. Therefore, simple rules could help to minimize the risk of medications incompatible with each other or with frequent genetic variants.Patients and Methods: One hundred and eighty-four multi-morbid Caucasian patients suffering from side effects or inefficient therapy were enrolled and genotyped. Their medication was analyzed by a team of specialists using Drug-PIN® (medication support system) and individual recommendations for 34 drug classes were generated.Results: In each of the critical drug classes, 50% of the drugs cannot be recommended to be prescribed in typical drug cocktails. PPIs and SSRI/SNRIs represent the most critical drug classes without showing a single favorable drug. Among the well-tolerated drugs (not recommended for less than 5% of the patients) are metamizole, celecoxib, olmesartan and famotidine. For each drug class, a ranking of active ingredients according to their suitability is presented.Conclusion: Genotyping and its profound analysis are not available in many settings today. The consideration of frequent alterations of metabolic elimination routes and drug–drug–gene interactions by using simple rankings can help to avoid many incompatibilities, side effects and inefficient therapies.Keywords: single nucleotide polymorphisms, personalized medicine, precision medicine, DDGIs, CYPs, transporter

[Abstract The Lake Izabal Basin in Guatemala is a major pull‐apart basin along the sinistral Polochic Fault, which is part of the North American and Caribbean plate boundary. The basin infill contains information about the tectonic and sedimentological processes that have imparted a significant control on its sedimentary section. The inception of the basin has been linked to the relative importance of the Polochic Fault in the tectonic history of the plate boundary; yet, its sedimentological record and its inception age have been poorly documented. This study integrates diverse datasets, including industry reports, well logs and reports, well cuttings, vintage seismic data, outcrop observations and geochronological data to constrain the initial infill and age of inception of the basin. The integrated data show that during the Oligocene–Miocene, a marine carbonate platform was established in the region which was later uplifted and eroded in the early Miocene. The fluvial–lacustrine deposits above this carbonate platform are part of the initial infill of the basin and are constrained with zircon weighted‐mean 206Pb/238U ages of 12.060 ± 0.008 from a volcanic tuff ~30 m above the unconformity. Sandstone, mudstone and coal dominate the interval from 12 to 4 Ma, with an increase in conglomerate correlating to the uplift of the Mico Mountains and San Gil Hill at 4 Ma. Fault switch activity between the Polochic and Motagua faults has been hypothesized to explain total offset along the Polochic Fault and the geologic and geodetic slip rates along the two faults. The 12 Ma age determined for the initial infill of the basin confirms this hypothesis. Consequently, our study confirms that at ~12 Ma the Polochic Fault served as the main fault of the plate boundary with inferred slip rates ranging from 13 to 21 mm/yr with a strong possibility that the Polochic Fault was, at some point between 15 Ma and 7 Ma, the only active fault of the plate boundary. The results of this study show that tectonic records preserved in sediments of strike‐slip basins improve the understanding of the relative significance of individual faults and the implications with respect to strain partitioning throughout its tectonic history., The Lake Izabal Basin initiated at 12 Ma. The Polochic Fault was the main plate boundary in the Miocene. Fault switch activity must have occurred along the plate boundary. ]

Aim of the study Botanicals used in Traditional Chinese Medicine (TCM) are a rich source for drug discovery and provide models for multi-component drug development. To facilitate the studies of the actions of TCM drugs and expand their applications, a comprehensive database is urgently required. Methods One online resource connects all the relevant data from multiple scientific sources and languages. Drug information from published TCM databases and the official Chinese Pharmacopoeia as well as specialized meta-websites such as Kew's Medicinal Plant Names Service was integrated on a higher level. Results Our database, SuperTCM, covers the aspects of TCM derived from medicinal plants, encompassing pharmacological recipes up to chemical compounds. It provides the information for 6516 TCM drugs (or "herbs") with 5372 botanical species, 55,772 active ingredients against 543 targets in 254 KEGG pathways associated with 8634 diseases. SuperTCM is freely available at http://tcm.charite.de/supertcm.

Marina Borro,1 Giovanna Gentile,1 Sally H Preissner,2 Leda Marina Pomes,1 Björn-Oliver Gohlke,3 Antonio Del Casale,4 Andreas Eckert,3 Paolo Marchetti,5 Saskia Preissner,2 Robert Preissner,3,6 Maurizio Simmaco1 1Department of Neurosciences, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University and Laboratory of Clinical Biochemistry, Sant’Andrea Hospital, Rome, Italy; 2Department Oral and Maxillofacial Surgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany; 3Science-IT and Institute of Physiology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany; 4Department of Clinical and Dynamic Psychology, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy; 5Medical Oncology Unit, Sant’Andrea Hospital, Rome, Italy; 6Drug-PIN AG, Lugano, SwitzerlandCorrespondence: Marina BorroDepartment of Neurosciences, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University and Laboratory of Clinical Biochemistry, Sant’Andrea Hospital, Via di Grottarossa 1035, Rome, ItalyTel +390633775457Fax +390633776664Email marina.borro@uniroma1.itPurpose: Inefficacy and safety concerns are main medications’ problems, especially in the case of poly-therapies, when drug–drug interactions may alter the expected drug disposition. Ongoing efforts are aimed to establish drug selection processes aimed to preemptive evaluation of a plethora of factors affecting patient’s specific drug response, including pharmacogenomic markers, in order to minimize prescription of improper medications. In previous years, we established at the University Hospital Sant’Andrea of Rome, Italy, a Precision Medicine Service based on a multi-disciplinary experts’ team. The team is in charge to produce a drug therapy counselling report, including pharmacogenomic, pharmacokinetic and pharmacodynamic considerations. In this study, we aimed to evaluate the performance of this established “manual” process of therapy selection with a novel bioinformatic tool, the Drug-PIN system.Patients and Methods: A total of 200 patients diagnosed with Major Depressive Disorders or a depressive episode in Bipolar Disorder, with at least three previous failed treatments, who underwent pharmacogenomic profiling and therapy counselling in the Sant’Andrea Hospital from 2017 to 2020. The baseline poly-therapy of these patients was re-evaluated and optimized by Drug-PIN. Results of the Drug-PIN poly-therapy evaluation/optimization were compared with the results of the original poly-therapy evaluation/optimization by therapy counselling. To compare the results between the two processes, the risk associated with each poly-therapy was classified as low, moderate, or high.Results: The number of baseline poly-therapies classified in low-, moderate- or high-risk did not change significantly between manual system or Drug-PIN system. As the counselling process, also the Drug-PIN system produces a significant decrease in the predicted treatment-associated risk.Conclusion: Drug-PIN substantially replicates the output of the counselling process, allowing a substantial reduction in the time needed for therapy evaluation. Availability of an effective bioinformatic tool for proper drug selection is expected to exponentially increase the actuation of targeted therapy strategies.Keywords: poly-therapy, pharmacogenomics, Precision Medicine, Drug-PIN, drug–drug interactions

BackgroundNumerous clinical trials have considered the potential linkages between statins and cancer. Despite some evidence for reduced mortality associated with statin use, the results thus far have been somewhat inconclusive and not easily comparable, thus hampering the emergence of a consensus. We suspect that this uncertainty would be reduced, and greater clarity achieved (e.g. regarding clinical best practices and standards-of-care), were we to have a reliable, causal biomarker that could help identify those individual patients who might benefit from statin use during cancer treatment.Methods and FindingsIn the joint experimental and statistical analysis reported here, we assessed the inhibitory potential of various statins on the expression of a tumor enhancer known as MACC1, taking into account the molecular functions of this key metastasis-associated protein. To assess any effects of statins in cancer prevention (observationally), we also performed a retrospective, two-center, nested case-control study, focusing on medical centers in Berlin, Germany and Virginia, USA. Among nearly a half-million patient visits, over a decade-long period, cancer patients were identified and analyzed in comparison to patients without cancer diagnoses. Odds ratios (OR) and hazard ratios (HR) for cancer were computed for patients with and without statin intake, accounting for potential confounders. Finally, we also extended these analyses of our trans-Atlantic cohort by utilizing real-world data from 132,072 cancer patients with statins available on the TriNetX platform.Experimental work revealed that statins inhibit MACC1 mRNA levels and protein expression, resulting in reduced MACC1-induced phenotypic functions, such as motility and proliferation. Moreover, we found that statins restrict colorectal cancer (CRC) growth and metastasis in xenografted mice. The cohort data that we gathered at the German and U.S. centers enabled analysis of 53,113 cancer patients and matched controls. These were extracted, aggregated, and 1:1 matched (by age/gender) in order to build propensity-score matched sub-cohorts, to mitigate confounder bias. Based on this real-world evidence (RWE), we found that atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin were associated with a 50% reduced overall risk for developing cancer (OR 0.5, CI 0.48-0.51). The strongest association of reduced cancer risk was found for (i) liver cancer (OR 0.35, 0.29-0.43), (ii) secondary neoplasms of respiratory and digestive organs (OR 0.42, 0.34-0.45), and (iii) colorectal cancer (OR 0.44, 0.39-0.5). The effect of atorvastatin (OR 0.3, 0.28-0.32) exceeded other considered statins, even after exclusion of aspirin as the strongest confounder (OR 0.63, CI 0.57-0.7). Additionally, we note that those patients taking statins have a 38% decreased risk of death (HR 0.64, 0.48-0.86).ConclusionsOur data, which offer evidence for cancer-preventative and anti-metastatic effects of statins, lead us to suggest that these medications should be considered in treating some types of cancers. In addition, MACC1 may serve as a potentially helpful biomarker for purposes of patient stratification (and personalized treatment). A more definitive test of these proposed ideas could come from prospective, randomized clinical trials.

Reliance on π-diagrams and tangent plots to describe fold geometry has created an unwarranted status for conical folds at the expense of periclines. Analysis of virtual periclines using synthetic stereograms, tangent diagrams, and geologic curvature analysis demonstrates small portions of periclines are “cylindrical.” The more significant “non-cylindrical” portion of periclines allows for a mathematically permissible, but unrealistic, geometrical representation as portions of cones. We demonstrate cones are an extremely poor geometric representation of both the virtual periclines and examples of natural non-cylindrical folds. “Conical folds,” if they exist, terminate at a point; the amplitude to width ratio and the plunge of the crestal line must remain constant towards the fold terminus, with a Gaussian curvature of zero. In contrast, the amplitude to width ratio, plunge along the crestal line, and Gaussian curvature of periclines vary towards the fold terminus. These differences have important implications for the rheological modeling of folds, and while realistic dynamic models for periclines exist, models for conical fold formation remain conceptual. We suggest that in order to advance our understanding of how folds form, it may be “pointless” to continue the misconception of conical folds as an accurate geometric representation of how folds end.

Flexural slip has long been recognized as a crucial mechanism during the development of chevron folds and a conceptual understanding of its role has been presented by analogue and kinematic models and field studies. This study uses 2D finite element analysis to provide a thorough quantitative evaluation of flexural slip based on buckling of effective single layers1 and true multilayers1. The analysis of the results describes the spatial and temporal evolution of flexural slip and documents the resulting fold shapes. The results show that effective single layer buckle folds amplifying the dominant wavelength, λd, do not result in chevron folds in any of the situations considered - varying initial perturbation, viscosity contrast and friction coefficient. Slip initiates early, and a transition from sinusoidal or parabolic to box folds is common. Reducing the amplified wavelength (~10% of λd), results in systematic chevron folds. For true multilayer buckle folds, systematic chevron folds featuring hinge collapse develop regardless of the initial perturbation used. The ratio of incompetent to competent layer thickness, s/h, is a crucial parameter: for s/h > 1, flow dominates and slip is not initiated; for s/h 53°) and that sinusoidal or parabolic folds nearly “instantaneously” change shape to chevron folds during a short period of slip initiation and termination, thus confirming the phenomenon of limb lock up. For models incorporating permeability contrasts, the development of deformation induced overpressure leads to an earlier initiation of flexural slip.

Graphical abstract, High-resolution visualization of surfaces of geologic interest, at a multitude of scales, using 3D point cloud technologies provides an opportunity to analyze spatial relationships of surfaces using orientation data. We present a MATLAB® script that produces planar geologic attitude data (e.g., strike, dip, and dip-direction data) from 3D datasets (e.g., point clouds, 3D scanning). The method utilizes Cartesian coordinates of triangular planar surfaces and converts them into matrices of conventional geologic attitude data. Spatial relationships among data points can be investigated, using polar tangent diagrams, stereographic analysis, or geologic curvature analysis. We utilize this script to create “synthetic” graphical plots (e.g., stereograms, tangent diagrams) from geomechanically realistic, virtual, folded surfaces produced by dynamic modeling. Synthetic graphical diagrams are of considerable usefulness in interpreting graphical plots (e.g., stereograms) of attitude data from natural folded rock surfaces, particularly in locations with poor exposure. • This script outputs attitude data (strike, dip, and dip direction) in a spreadsheet and as a text file for use in other visualization software. • A tangent diagram is created and displayed in this script for rapid visualization and fold shape assessment. • The MATLAB script is readily modified to accept multiple data formats for input (e.g., MATLAB variables, *.csv files, etc.) and output (e.g., *.csv files, *.txt files, etc.).

The characterization of folds is often limited to two-dimensional cross-sectional views where folds are approximated as cylindrical. This enables simplification of fold shape analysis (using principles such as dip isogons, stereographs, tangent diagrams, and Bezier curve analysis), allows for a simplified analysis of the distribution of stress and strain, and enables and the analysis and visualization of folding associated fractures. However, in a heterogenous medium folds have to terminate somewhere, resulting in more complex three-dimensional geometries. In this study, a 3D finite element modeling approach using a Maxwell visco-elastic rheology is utilized to simulate 3D periclinal folds resulting from single layer buckle folding. With respect to fold shape analysis, we use the forward modeled pericline geometries to demonstrate that geometrical attitude data collected for various cross sections and plotted using traditional 2D methods such as stereographs and tangent diagrams may lead to the misinterpretation of the fold shape as conical. In contrast 3D geometric data such as Gaussian curvature can describe and quantify the 3D fold geometry in its entirety. With respect to folding associated fracture analysis, the 3D modeling results show that shear fractures of various orientations in the fold limb, which cannot be intuitively explained by the strain/stress regimes during 2D buckling and require unrealistic boundary conditions, are feasible to occur during a single deformation event during the development of a pericline. In summary, accounting for the true 3D geometry of buckle fold structures will lead to a better classification of folds, a better understanding of the processes and parameters affecting their development, and enable post-folding failure analysis.