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Hintergrund: Die Perspektive von Betroffenen ist wesentlich für eine Berücksichtigung von patientenrelevanten Fragen und die Identifikation von Versorgungslücken bei der Auswahl der Ziele einzelner Forschungsprojekte. Faktisch ist allerdings eine konsequente Umsetzung der Patientenbeteiligung insbesondere dann schwierig, wenn bereits zu Beginn der Partizipation wesentliche Eckpunkte des Projekts wie die Forschungsfrage gesetzt sind. Während Patientenbeteiligung an der Entwicklung und Durchführung von Forschungsvorhaben im Gesundheitswesen mittlerweile vielfach akzeptiert ist, scheint patienteninitiierte Forschung weiterhin eher selten zu sein. Material und Methoden: Narrative Übersichtsarbeit. Ergebnisse und Diskussion: Patientenbeteiligung ist nicht nur ein ethisch und sozial gebotenes Desiderat; es profitieren unmittelbar auch die Forschung und die Forschenden selbst. Selbsthilfegruppen könnten gezielt dazu beitragen, Bottom-up-Forschungsbedarf und -fragen zu identifizieren, zu sammeln und weiterzugeben. Die Arbeitsgemeinschaft Prävention und Integrative Onkologie (PRiO) konnte zusammen mit den beiden Arbeitsgemeinschaften für Soziale Arbeit (ASO) und Konferenz der Onkologischen Krankenpflege (KOK) im Rahmen von Doktorandenprojekten in den vergangenen Jahren viele kleine patienteninitiierte Forschungsarbeiten durchführen. Die systematische Integration von patienteninitiierter Forschung sowie eine strukturierte Themensuche könnten ein lohnenswertes Ziel sein. Auch wenn es viele Ressourcen erfordern wird und die Gefahr einer Überregulierung mit sich bringen könnte, die den „einfachen“ Menschen nicht mehr zum Zuge kommen lässt. Dem gegenüber steht eine zielgerichtete Ausrichtung von Fragestellungen in realen Versorgungssituationen durch Fragestellungen von betroffenen Personen.

An efficient synthesis of the novel {6-[1,1-di(pyridin-2-yl)ethyl]pyridine-2-yl}2-methyl-1,3-propanediamine (2) is reported, as well as a reliable large-scale synthesis (of the order of 100 g) of previously known 2,2’-[1-(6-chloropyridin-2-yl)ethane-1,1-diyl]dipyridine (4); the latter is the starting material for the preparation of the former, as well as a multitude of other polypodal polyamine/polyimine ligands. Both materials, as well as the intermediates in their multi-step syntheses, have been fully characterised. Ligand 2, in conjunction with ligands 2,2’-(pyridine-2,6-diyl)bis(2-methylpropane-1,3-diamine) (1) and 2,6-bis(1,1-di(pyridin-2-yl)ethyl)pyridine (3), establishes a series of tetrapodal pentadentate N5ligands Lof like scaffold, and thus coordination geometry, but graded primary amine/imine donor atom ratios. The iron(II) complexes [Fe(L)NCCH3](OTf)2(L= 1: A; L= 2: B; L= 3: C; OTf = triflate) have been prepared and fully characterised, including X-ray single-crystal structure analyses. The metal-centred one-electron oxidation/reduction potential (FeII/FeIII) depends sensitively on the electron donor capacity of the capping ligand used, as demonstrated by cyclic voltammetry. Whereas the acetonitrile ligand in Aand Cis readily exchanged for a methanol ligand in methanol solution, the resulting complexes showing variable-temperature spin crossover (SCO) in solution, Bhas been found to be inert to this type of ligand exchange.

ABSTRACTWhen Derrida translated and commented on Husserl’s manuscript The Origin of Geometryin 1962, he gave a central place to what Husserl called the Idea “in the Kantian sense”. This article reflects on the use and function of this Idea in Derrida’s reading of Husserl. It critically interrogates the relationship between the Idea in the Kantian sense and mathematical ideality, as well as the use of this Idea in the interpretation of the Thing (Ding) and the stream of experience (Erlebnisstrom). In the centre of the discussion stands what Derrida calls “pure thinking”, on which he tries to ground the Idea in the Kantian sense.

ABSTRACTCeratonia siliquaL. belonging to the Leguminosae(Fabaceae) family, has been cultivated for millennia and is recognized as a valuable botanical resource. However, global production of this tree is rapidly declining. This paper aims to examine the primary uses of carob trees and highlight their value in the landscape by developing a systematic review of Scopus documents from 1980 to 2023. The resulting 2130 documents revealed that the main studied uses of carob trees are in human medicine and food. Additionally, 3.85% of these documents studied the landscape value of carob trees, emphasizing their role in improving landscape resilience, preserving rural identities, and fostering the development of geo-specific strategies for slow tourism. This systematic review underscores the multifaceted importance of Ceratonia siliquaL. in both cultural and environmental contexts, advocating for its preservation and sustainable use.

Neuronale Netze ermöglichen eine flexible und anpassungsfähige Verarbeitung von Informationen. Daher eignen sie sich besonders für komplexe Aufgaben wie Bilderkennung oder Erstellung von Prognosemodellen. Durch den Einsatz dieser Konzepte kann künstliche Intelligenz (KI) dazu beitragen, präzisere Diagnosen zu stellen, individuelle Behandlungspläne zu erstellen und die Effizienz der Therapie zu verbessern. Vielversprechend ist die Anwendung der KI in der bildgebenden Diagnostik zur Detektion von Lungenrundherden und der Einsatz im Bereich des Lungenkrebs-Screenings. Neben der Vorhersage von Nebenwirkungswahrscheinlichkeiten ist der Einsatz von KI auch für die Prädiktion des Ansprechens auf die Strahlentherapie und in der Nachsorge von Interesse. Beispielsweise erwies sich in der individualisierten Therapienachsorge von Patienten mit Lungenkarzinom die Verwendung einer webbasierten Applikation mit integriertem Risikobewertungsalgorithmus auf der Grundlage einer wöchentlichen Symptomerfassung durch die Patienten als vorteilhaft gegenüber der nichtindividualisierten Nachsorge, da ein längeres Gesamtüberleben durch frühere Rezidiverkennung und ein besserer klinischer Allgemeinzustand erreicht wurden.

We present a practical approach to intercompare a range of candidate digital elevation models (DEMs) based on predefined criteria and a statistically sound ranking approach. The presented approach integrates the randomized complete block design (RCBD) into a novel framework for DEM comparison. The method presented provides a flexible, statistically sound, and customizable tool for evaluating the quality of any raster—in this case, a DEM—by means of a ranking approach, which takes into account a confidence level and can use both quantitative and qualitative criteria. The users can design their own criteria for the quality evaluation in relation to their specific needs. The application of the RCBD method to rank six $1''$ global DEMs, considering a wide set of study sites, covering different morphological and land cover settings, highlights the potentialities of the approach. We used a suite of criteria relating to the differences in the elevation, slope, and roughness distributions compared to reference DEMs aggregated from 1- to 5-m light detection and ranging (LiDAR)-derived DEMs. Results confirmed the significant superiority of Copernicus DEM (CopDEM) $1''$ and its derivative forests and buildings removed DEM (FABDEM) as the overall best $1''$ global DEMs. They are slightly better than Advanced Land Observing Satellite (ALOS) and clearly outperform NASADEM and SRTM, which are, in turn, much better than advanced spaceborne thermal emission and reflection radiometer (ASTER).

Die Partizipation von Patient*innen an der Planung, Durchführung und Evaluation versorgungsrelevanter Forschungsvorhaben zielt auf die Optimierung der onkologischen Versorgung. Sie kann in allen Phasen des gesamten Forschungsprozesses oder punktuell erfolgen. Die Aufgaben, die im Rahmen der Partizipation anstehen, sollten frühzeitig konkretisiert werden, um geeignete Personen für die Zusammenarbeit zu gewinnen. Als weitere Voraussetzung für das Gelingen der Zusammenarbeit sind potenzielle personelle und strukturelle Barrieren zu identifizieren und zu adressieren. Alle Beteiligten sollten auf die Zusammenarbeit vorbereitet sein. Auch sollte die Finanzierung der Projekte die erforderlichen finanziellen Mittel für die Einbeziehung der Patient*innen berücksichtigen. Ein Beitrag aus der Praxis zeigt, wie Partizipation gelingen kann.

AbstractSituated in the context of the climate crisis this research examines the LVMH Corporation’s 2020 and 2021 Social and Environmental Responsibility Reports through the lens of the narrative structure found in fairy tales. Central characters and the trajectory of the narrative are consistent with this literary form, and counter narratives that provide context to the corporate narrative also emerge. This analysis suggests the significance of narratives to corporate communications, their application extending beyond the brand communication or user-generated content generally investigated in the marketing and consumer research literature. Moreover, the article elaborates on how luxury corporations, like LVMH, communicate their efforts to counter climate crisis in ways that meet the expectations of stakeholders, especially investors and consumers. The findings have implications for future research on how narratives impact stakeholder perceptions of luxury corporations.

Single-molecule Förster-resonance energy transfer (smFRET) experiments allow the study of biomolecular structure and dynamics in vitro and in vivo. We performed an international blind study involving 19 laboratories to assess the uncertainty of FRET experiments for proteins with respect to the measured FRET efficiency histograms, determination of distances, and the detection and quantification of structural dynamics. Using two protein systems with distinct conformational changes and dynamics, we obtained an uncertainty of the FRET efficiency ≤0.06, corresponding to an interdye distance precision of ≤2 Å and accuracy of ≤5 Å. We further discuss the limits for detecting fluctuations in this distance range and how to identify dye perturbations. Our work demonstrates the ability of smFRET experiments to simultaneously measure distances and avoid the averaging of conformational dynamics for realistic protein systems, highlighting its importance in the expanding toolbox of integrative structural biology.

4-(2,6-Di(2H-indazol-2-yl)pyridin-4-yl)benzoic acid (1) and 10-(2,6-di(1H-pyrazol-1-yl)pyridin-4-yl)anthracene-9-carboxylic acid (2) were required for adsorption studies on Ag(111), with a view to subsequent iron(II) complexation and formation of well-ordered spin-responsive self-assembled monolayers. While the generation of these compounds has remained elusive, several intermediates and by-products were obtained, potentially useful as dipyrazolylpyridine-related derivatives and for metal ion coordination. 3,5-Dichloro-2,6-diindazolylpyridine-4-amine, which forms as a mixture of regioisomers, was synthesised, the mixture separated, and the components characterised (3,5-dichloro-2,6-di(2H-indazol-2-yl)pyridin-4-amine; 3,5-dichloro-2-(1H-indazol-1-yl)-6-(2H-indazol-2-yl)pyridin-4-amine; 3,5-dichloro-2,6-di(1H-indazol-1-yl)pyridin-4-amine). Their iron(II) complexes have been prepared and fully characterised, including single crystal X-ray structure determination. The complexes are instructive examples of the influence of ligand design (“steric jamming”) on the spin-crossover (SCO) activity of FeIIcentres. Bulky substitution, which entails twisted ligand conformation, increases intramolecular crowding. This prevents contraction of the metal coordination sphere, which would be a prerequisite for thermally inducible SCO. Mössbauer spectroscopy has revealed that the complexes remain predominantly high-spin (HS) between 20 and 200 K, and that a mixture of conformational HS isomers is present in the microcrystalline solid.

Ribosomal RNA (rRNA) maturation in archaea is a complex multistep process that requires well-defined endo- and exoribonuclease activities to generate fully mature linear rRNAs. However, technical challenges prevented detailed mapping of rRNA processing steps and a systematic analysis of rRNA maturation pathways across the tree of life. In this study, we used long-read (PCR)-cDNA and direct RNA nanopore-based sequencing to study rRNA maturation in three archaeal model organisms, namely the Euryarchaea Haloferax volcaniiand Pyrococcus furiosusand the Crenarchaeon Sulfolobus acidocaldarius. Compared to standard short-read protocols, nanopore sequencing facilitates simultaneous readout of 5′- and 3′-positions, which is required for the classification of rRNA processing intermediates. More specifically, we (i) accurately detect and describe rRNA maturation stages by analysis of terminal read positions of cDNA reads and thereupon (ii) explore the stage-dependent installation of the KsgA-mediated dimethylations in H. volcaniiusing base-calling and signal characteristics of direct RNA reads. Due to the single-molecule sequencing capacity of nanopore sequencing, we could detect hitherto unknown intermediates with high confidence, revealing details about the maturation of archaea-specific circular rRNA intermediates. Taken together, our study delineates common principles and unique features of rRNA processing in euryarchaeal and crenarchaeal representatives, thereby significantly expanding our understanding of rRNA maturation pathways in archaea.

Over the last five years, all major cloud platform providers have increased their serverless offerings. Many early adopters report significant benefits for serverless-based over traditional applications, and many companies are considering moving to serverless themselves. However, currently there exist only few, scattered, and sometimes even conflicting reports on when serverless applications are well suited and what the best practices for their implementation are. We address this problem in the present study about the state of serverless applications. We collect descriptions of 89 serverless applications from open-source projects, academic literature, industrial literature, and domain-specific feedback. We analyze 16 characteristics that describe why and when successful adopters are using serverless applications, and how they are building them. We further compare the results of our characterization study to 10 existing, mostly industrial, studies and datasets; this allows us to identify points of consensus across multiple studies, investigate points of disagreement, and overall confirm the validity of our results. The results of this study can help managers to decide if they should adopt serverless technology, engineers to learn about current practices of building serverless applications, and researchers and platform providers to better understand the current landscape of serverless applications.

Tryptophan hydroxylases catalyze the first and rate-limiting step in the synthesis of serotonin. Serotonin is a key neurotransmitter in the central nervous system and, in the periphery, functions as a local hormone with multiple physiological functions. Studies in genetically altered mouse models have shown that dysregulation of peripheral serotonin levels leads to metabolic, inflammatory, and fibrotic diseases. Overproduction of serotonin by tumor cells causes severe symptoms typical for the carcinoid syndrome, and tryptophan hydroxylase inhibitors are already in clinical use for patients suffering from this disease. Here, we describe a novel class of potent tryptophan hydroxylase inhibitors, characterized by spanning all active binding sites important for catalysis, specifically those of the cosubstrate pterin, the substrate tryptophan as well as directly chelating the catalytic iron ion. The inhibitors were designed to efficiently reduce serotonin in the periphery while not passing the blood–brain barrier, thus preserving serotonin levels in the brain.

Background: The aim is to assess the levels of fatty acids (FAs) in pregnancies with small for gestational age (SGA) and adequate for gestational age (AGA) fetuses, constituting an association between FAs and fetal growth; according to the role of FA, lower levels were expected in SGA. Materials and Methods: This was an analytical cross-sectional study including pregnant women with gestational ages of 26–36 weeks with AGA and constitutionally SGA fetuses diagnosed by ultrasonography. The levels of saturated, trans, monounsaturated, and polyunsaturated fatty acids were measured using centrifugation and liquid chromatography. Student’s ttest and general linear model using gestational age as covariant were used to compare the levels of FAs and the groups (AGA and SGA). Chi-square was used to evaluate the association between groups and studied variables. Pearson correlation coefficient and linear regression were used to evaluate the correlation between the levels of FAs and gestational age. Results: Peripheral blood was collected from 67 pregnant women, 3 of whom were excluded from the study. No significant statistical differences were observed between SGA (n= 40) and AGA (n= 24) in relation to saturated, trans, monounsaturated, and polyunsaturated fatty acids (p> 0.05). There was not significant correlation between saturated, trans, monounsaturated, and polyunsaturated FAs and gestational age (p> 0.05). Conclusion: The levels of saturated, trans, monounsaturated, and polyunsaturated FAs were similar in constitutionally SGA and AGA fetuses.

We report the chelation-assisted oxidative CH2extrusion from a PtII-coordinated dipyridylmethane, resulting in the formation of a 2,2′-bipyridyl ligand. This unusual one-pot reaction (solvent: dimethylformamide, DMF), which is quantitative, proceeds in air at mildly elevated temperature, with CH2→ C=O conversion, decarbonylation, and ipso-ipsoC–C coupling of the two pyridyl residues (“fragment coupling”). It constitutes, in effect, a chelate ring contraction by one member.

Mortality rates in all phases of pork production have increased over the past several years. Decreasing mortality rate is of utmost economic importance to producers, especially in weaning-to-finishing pigs where additional investment in feed, medications, and other inputs are expended. A novel analytical method was used to identify sequences of days of increased mortality, defined as mortality episodes, within cohorts of weaning-to-finishing pigs. Cubic smoothing spline regression equations were estimated between days post placement (DPP) and mortality (total daily number of dead and euthanized pigs) for 42 groups of pigs placed in 12 rooms within 6 barns (2 rooms per barn) in Illinois and Iowa from December 2020 to July 2022 (n = 5,676 observation days). For each group, the instantaneous slope between DPP and mortality from spline regression was calculated and used to identify changepoints [i.e., peaks (negative instantaneous slope at DPPtand positive instantaneous slope at DPPt-1) and valleys (positive instantaneous slope at DPPtand negative instantaneous slope at DPPt-1)]. Within each mortality sequence, the maximum and minimum instantaneous slope were considered the start and end of the mortality episode, respectively. Mortality episodes were only considered high mortality episodes if the following metrics were satisfied: 1) greater than or equal to 1 mortality per day, or 2) greater than or equal to 1/3 of the days in the mortality sequence had at least 1 mortality. Days were classified as “start days” if they were within 1 d from the maximum instantaneous slope; likewise, we classified a day as “end days” if it was 1 d from the minimum instantaneous slope. Any day in between the start and end of a mortality episode were defined as “peak days”, and a “normal day” was all other days that did not fall within the start, peak, or end of a high mortality episode. Least-squares means for predicted mortality from a negative binomial generalized linear model showed that mortality was highest and lowest for peak days and normal days, respectively (3.475 ± 0.1729 and 0.591 ± 0.0156 pigs, respectively; P< 0.05; Table 1). Mortality during start or end days of an episode did not differ from each other (2.185 ± 0.1973 and 2.069 ± 0.1881 pigs, respectively; P> 0.05; Table 1) but were significantly greater and lower than a normal or peak day, respectively (P< 0.05; Table 1). The proposed analytical method provides more precise classification of mortality episodes in pig cohorts than previously proposed methods. Results from this method can be used in models to predict the start of mortality episodes, providing ample time for intervention to reduce the overall number of dead pigs in wean-to-finish pig production.

There is sufficient evidence that adequate feed and water consumption during the lactation period positively influences sow body condition at weaning. Optimum body condition score after the lactation period decreases sow wean-to-estrus interval and non-productive sow days and promotes sow reproductive performance in the following reproductive cycle, in general. However, feed and water intake patterns have not been extensively studied in commercial sow research; thus, the objective of this study was to determine the effect of feed and water consumption patterns in the lactation period on wean-to-estrus interval in weaned sows. This trial was conducted in a commercial sow farm located in southwestern Minnesota in March 2023. Each lactation feeder was outfitted with a MealMeter 2.0 device (PigEasy, LLC, Templeton, IA), which uses a rotating feed dispenser to release feed ad libitum at the request of each sow. In addition, the MealMeter 2.0 device utilizes sensors to track the number of times feed and water were accessed at 15-min time intervals across the entire lactation period. Average daily feed (ADF) and water accessions (ADW) were summarized for each sow during the lactation period (n = 84 sows). Root mean squared error (RMSEFand RMSEWfor feed and water accessions, respectively) was calculated from the residuals of the regression between days post-farrowing and ADF and ADW for each sow and was considered a measure of variation in feed and water accessions during the lactation period. Moreover, the number of days from weaning to the first estrus was recorded and defined as the wean-to-estrus interval (WTE). Due to the distribution of WTE, sows with a WTE ≤ 5 d and WTE > 5 d were separated into a binary classifier (0 = WTE ≤ 5 d and 1 = WTE > 5 d). The relationship between each feed and water measurement and WTE class was estimated using a logistic regression model fit with R Statistical Software. Average daily feed and water accessions were negatively associated with WTE class (P- = 0.07 and 0.04, respectively; Table 1), indicating that as feed and water accessions increase, the probability of observing a WTE greater than 5 d decreases. In addition, RMSEFand RMSEWwere also negatively associated with WTE class, which suggests that as the variation in each measure across the lactation period increases, the probability of observing a WTE greater than 5 d is reduced. This result was not expected and, thus, requires further investigation. Nonetheless, results from this study suggest that the mean and variation of daily feed and water accessions are associated with WTE and sufficient consumption of nutrients during the lactation period is critical to reducing the number of days to first estrus in weaned sows.

In the swine industry, boar nutritional requirements are not well characterized; thus, boars are typically fed to maintain a specific body condition score (BCS). Assessing body condition with subjective scoring can lead to over or underfeeding, which may have repercussions on sperm production and(or) quality. There are objective tools to assess body condition in live boars, like backfat (BF) thickness measured with real-time ultrasound, the Knauer caliper, and flank-to-flank (F2F) length. The relationship of sperm production and quality with BCS has not been reported in modern genetics and modern boar studs. The purpose of this study was to evaluate the relationship of body condition measures with boar reproductive performance. Data collected in March 2023 on commercial boars (n = 147) included a BCS ranging from 2.25 to 3.5, ultrasound backfat (13.7 ± 4.37 mm) performed by a trained technician, body weight (BW; 222 ± 30.2 kg) estimated using heart girth and body length from poll to tailhead, F2F length (106.03 ± 5.94 cm) and Knauer caliper score (17.5 ± 2.37). Additional variables considered were boar genetic line, age, and collection frequency. Sperm production data (total motility, 92.1 ± 7.22%; concentration, 36.7 ± 12.10 mil/mL; ejaculate volume, 231.1 ± 73.72 mL; normal cells, 83.4 ± 11.27%) were obtained from the six collections immediately prior to body condition evaluation. Data were evaluated with the glmmTMB package of R Statistical Software using a generalized linear mixed model. There were no significant relationships between motility or ejaculate volume and boar body condition. Backfat depth was related to percentage of normal cells (P= 0.029) and inversely related to sperm concentration (P= 0.035). There was a tendency for boars with greater F2F to have greater sperm concentration (P= 0.090). Generally, the percentage of normal cells decreased with increasing BCS, though due to the low number of observations in the lower categories, only BCS 3.25 and BCS 3.5 boars were found to have a significant relationship with the trait (P= 0.004 and P= 0.022, respectively). Caliper measure was not related with any sperm parameters. While accessible tools are necessary for consistent management of boars, BF thickness measured by ultrasound was the only objective tool in this study with a significant relationship to any sperm parameters assessed. Measuring BF with ultrasound may not be practical for everyday use. More research should be done to further assess body condition measurements, objective measuring tools, and boar sperm production.

High-throughput sequencing dramatically changed our view of transcriptome architectures and allowed for ground-breaking discoveries in RNA biology. Recently, sequencing of full-length transcripts based on the single-molecule sequencing platform from Oxford Nanopore Technologies (ONT) was introduced and is widely used to sequence eukaryotic and viral RNAs. However, experimental approaches implementing this technique for prokaryotic transcriptomes remain scarce. Here, we present an experimental and bioinformatic workflow for ONT RNA-seq in the bacterial model organism Escherichia coli, which can be applied to any microorganism. Our study highlights critical steps of library preparation and computational analysis and compares the results to gold standards in the field. Furthermore, we comprehensively evaluate the applicability and advantages of different ONT-based RNA sequencing protocols, including direct RNA, direct cDNA, and PCR-cDNA. We find that (PCR)-cDNA-seq offers improved yield and accuracy compared to direct RNA sequencing. Notably, (PCR)-cDNA-seq is suitable for quantitative measurements and can be readily used for simultaneous and accurate detection of transcript 5′ and 3′ boundaries, analysis of transcriptional units, and transcriptional heterogeneity. In summary, based on our comprehensive study, we show nanopore RNA-seq to be a ready-to-use tool allowing rapid, cost-effective, and accurate annotation of multiple transcriptomic features. Thereby nanopore RNA-seq holds the potential to become a valuable alternative method for RNA analysis in prokaryotes.

Chronic kidney disease (CKD) is a major health-care burden. Increasing evidence suggests that a considerable proportion of patients are affected by a monogenic kidney disorder.

Why do so many companies adopt serverless? When are serverless applications well suited? How are they currently implemented? To address these questions, we analyze 89 serverless applications from open source projects, industrial sources, academic literature, and scientific computing-presenting the most extensive study to date.

As vixotrigine (1) entered a later clinical phase for trigeminal neuralgia (Zakrzewska, J. M.; et al. Lancet Neurol.2017, 16, 291−300), the development of a sustainable late-stage process was required to meet the supply needs for formulation optimization, phase 3 clinical trials, and registration stability batches (this is the expected commercial formulation). In this article, we describe how the process was streamlined from the early supply route (Giblin, G.; et al. Org. Process Res. Dev.2020, DOI: 10.1021/acs.oprd.0c00382) and a comprehensive control strategy was established. Process improvements included improving safety and scalability for a temperature-sensitive Grignard reaction, simplifying unit operations, removal of heterogenous conditions, and route redesign to afford a high yielding, one-pot sequential alkylation and amidation. Improvement in the salt formation step, combined with wet milling, resulted in improved particle properties with enhanced flow properties of the final active pharmaceutical ingredient. The process mass intensity was improved 65% while maintaining drug substance purity at more than 99.8%. This new process has been scaled up to generate metric ton quantities of drug substance.

This article introduces the Seshat: Global History Databank, its potential, and its methodology. Seshat is a databank containing vast amounts of quantitative data buttressed by qualitative nuance for a large sample of historical and archaeological polities. The sample is global in scope and covers the period from the Neolithic Revolution to the Industrial Revolution. Seshat allows scholars to capture dynamic processes and to test theories about the co-evolution (or not) of social scale and complexity, agriculture, warfare, religion, and any number of such Big Questions. Seshat is rapidly becoming a massive resource for innovative cross-cultural and cross-disciplinary research. Seshat is part of a growing trend to use comparative historical data on a large scale and contributes as such to a growing consilience between the humanities and social sciences. Seshat is underpinned by a robust and transparent workflow to ensure the ever growing dataset is of high quality.

This study aimed to evaluate, histomorphometrically, the use of collagen matrix (CM) and/or enamel matrix derivative (EMD) for the treatment of dehiscence‐type recession defects in minipigs. Eight healthy, male, young BR‐1 minipigs, with no periodontal disease were treated. Bilateral dehiscence‐type defects were surgically created on the buccal of the mandibular premolars (PI and PII). After 30 days, the defects were randomly assigned to four groups: coronally advanced flap (CAF); CAF + CM; CAF + EMD; and CAF + CM + EMD (split‐mouth design). The evaluated parameters (mm): total defect length; new cementum (NC); new bone (NB); gingival margin position; total epithelium length; epithelium on the root; connective tissue adaptation; and soft tissue thickness (STT). The EMD‐treated groups showed a superior length of NC [4.13 ± 1.22 (CAF + EMD); 3.95 ± 1.11 (CAF + CM + EMD); 2.94 ± 0.77 (CAF + CM); 2.72 ± 0.81 (CAF), P= 0.02] and NB [3.21 ± 0.68 (CAF + CM + EMD); 3.01 ± 0.56 (CAF + EMD); 2.15 ± 0.47 (CAF + CM); 2.29 ± 0.82 (CAF), P= 0.005]. The CAF and CAF + CM groups showed a superior epithelial length when compared to EMD‐treated groups after 3 months. A superior STT was observed for CAF + CM + EMD group (1.5 ± 0.33) when compared with the other groups [1.09 ± 0.26 (CAF + EMD); 1.04 ± 0.34 (CAF + CM); and 1.14 ± 0.29 (CAF), P= 0.03]. The results of the present study indicate that EMD application, irrespective of the combination with CM, may improve the periodontal regeneration of dehiscence‐type defects in this animal model.