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PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

In this work, we simulate barchan swarms using the Two-Flank Agent-Based Model and investigate how changes to model parameters and environmental drivers lead to different swarm dynamics. In particular, we explore how the parameter qshift, which controls the rate of equilibration between the flanks of an asymmetric dune and thereby the stability of an asymmetric morphology, influences the frequencies of different collision types in the swarm and can be adjusted to produce swarms with dune sizes that are longitudinally homogeneous. Such size stability has been observed in real-world swarms but has not been obtained by previous agent-based models. We also find that, for certain densities of newly added barchans, the dune number density remains constant with downwind distance, something which has also been reported in nature but not in previous agent-based models. We also investigated how boundary condition changes propagate through swarms, something which will become increasingly important in the face of human infrastructure expansion and anthropogenic climate change. Finally, we are able to investigate how asymmetry and spatially patterning in the swarms are influenced by bimodal wind regimes. Since these simulations produce many more realistic phenomena than previous models, this work represents a significant step forward in the our understanding of the interplay between environmental conditions and dune interactions in shaping the dynamics of barchan swarms.

Giulia Zago,1,2,* Mirte Muller,1,* Michel van den Heuvel,1 Paul Baas1 1Department of Thoracic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek (NKI-AvL), Amsterdam, the Netherlands; 2Medical Oncology 2, Istituto Oncologico Veneto (IOV), Padova, Italy *These authors contributed equally to this work Abstract: Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017) and non-squamous NSCLC (CheckMate 057). In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively). Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors. Keywords: nivolumab, advanced non-small-cell lung cancer, immunotherapy, anti-PD-1

Students exit calculus with understandings of change that want for conceptual depth and are disconnected from real-world contexts. In this paper, we present a problem that will develop their skills in using "change" concepts for learning differential equations through modelling. The problem comes from a qualitative study of how STEM majors approach and think about differential equations as models for real-world scenarios. Our purpose is to inform faculty who are using open, authentic, scenario-driven instructional materials about the ways their students think about what are often taken-for-granted concepts in advanced mathematics and to support faculty in ensuring their students get the most from their innovative instructional materials.

Abstract Striated grooves in tool marks are common at the base of sandstones, especially in deep‐marine successions, but their use in physical‐process and environmental reconstruction is underdeveloped. To fill this gap in knowledge, striations in the central groove of chevron marks and in chevron‐less groove marks were formed in the laboratory by dragging tools armoured with silt, sand or gravel across muddy substrates. These experiments simulated the formation of striated grooves by armoured mud clasts carried at the base of quasi‐laminar and fully laminar debris flows, aiming to: (1) delineate the bed shear strengths for the formation of striated grooves at different armour sediment sizes; (2) examine how the preservation potential of striated grooves depends on clay bed rheology and size of armour sediment and (3) discuss how the pre‐lithification clay bed consolidation state and size of armour sediment can be reconstructed from striated grooves in the geological record. The experimental results revealed that tools with small‐diameter silt and sand armours dragged along soft beds lack striations or, at best, leave poorly defined striations, whereas firm beds and gravel armours exhibit well‐defined striations. The spacing of striations formed by gravel clasts corresponds well with the clast diameter, implying that striation spacing is a good proxy for the diameter of armoured gravel under natural conditions. In contrast, the spacing of striae formed by sand armours is greater than the grain diameter, suggesting that the spacing of fine striations can only be used to predict a maximum armour sand size. A comparison of different processes of formation of armoured mud clasts demonstrated that the armouring of mud clasts most probably happens after incorporation of the clasts by erosion into the head of the debris flow and subsequent movement across a loose sandy or gravelly bed surface.

Abstract A precise quantification of mitral regurgitation (MR) severity is essential for treatment and outcome of patients with MR. 3D echocardiography facilitates estimation of MR but selection of patients with necessity of invasive treatment remains challenging. We investigate effective regurgitation orifice area (EROA) quantification by 3D compared to 2D echocardiography in patients with MR and highlight the improved discrimination of MR severity. We consecutively enrolled fifty patients with primary or secondary and at least moderate MR undergoing 2D and 3D colour Doppler echocardiography prior to transcatheter edge-to-edge repair (TEER). Improved accuracy of MR grading using 3D vena contracta area (VCA) as an estimate of EROA was compared to 2D proximal isovelocity surface area (PISA) quantification method and a multiparameter reference standard. Quantification of EROA remarkably varies between 2D and 3D echocardiography and the discrimination between moderate and severe MR was significantly (p = 0.001) different using 2D PISA or 3D VCA, respectively. 3D VCA correlated significantly (r = 0.501, p

(Series Information) European Papers - A Journal on Law and Integration, 2024 9(1), 209-228 | Article | (Table of Contents) I. Introduction. – II. The two-step accession to Schengen. – II.1. Schengen accession under primary law. – II.2. Schengen accession under secondary law. – III. Application of the Schengen acquis in Schengen candidate states. – III.1. Binding but not applicable. – III.2. Defining Schengen’s external borders. – III.3. The legal regime at the Schengen state’s border with Schengen candidate countries. – IV. Participation without full membership. – V. Conclusion. | (Abstract) This Article looks at the practical and legal implications of the Schengen “waiting room”. It examines the rules that apply to the verification of readiness in preparation of a Council decision on full accession and the extent to which the rules of the Schengen acquis apply to Schengen Candidate Countries prior to the lifting of internal border controls. It pays particular attention to the legal regime that applies at the borders between “old” and “new” Member States, more specifically Schengen members and Schengen Candidate Countries, and the borders between the Schengen Candidate Countries and third countries. It is argued that the prolonged exclusion from the Schengen area has resulted in a de facto duplication of the EU’s external border, accompanied with an incremental, near full application of the Schengen acquis, short of lifting internal border controls. As a result, for already well over fifteen years, Romania and Bulgaria have been part of the accompanying measures that should allow for free travel, yet its nationals have not been able to enjoy the benefits of their EU citizenship in full.

Background: Glycoprotein (GP)VI is a platelet-specific collagen receptor required for platelet activation during hemostasis. Platelet reactivity toward collagen is routinely assessed during diagnostic workup of platelet disorders. GPVI can be activated by inducing receptor clustering with suspensions of fibrillar collagen or synthetic cross-linked collagen-related peptide (CRP-XL). However, these suspensions are poorly standardized or difficult to produce. Nanobodies are small recombinant camelid-derived heavy-chain antibody variable regions. They are highly stable, specific, and ideal candidates for developing a stable GPVI agonist for diagnostic assays. Objectives: Develop a stable nanobody-based GPVI agonist. Methods: Nanobody D2 (NbD2) was produced as dimers and purified. Tetramers were generated via C-terminal fusion of dimers with click chemistry. Nanobody constructs were functionally characterized with light transmission aggregometry (LTA) in platelet-rich plasma and whole blood flow cytometry. Diagnostic performance was assessed in patients with inherited platelet function disorders with LTA and flow cytometry. Results: NbD2 was specific for human platelet GPVI. Dimers did not result in platelet activation in LTA or flow cytometry settings and fully inhibited CRP-XL-induced P-selectin expression and fibrinogen binding in whole blood and attenuated collagen-induced platelet aggregation in platelet-rich plasma. However, NbD2 tetramers caused full platelet aggregation, as well as P-selectin expression and fibrinogen binding. NbD2 tetramers were able to discriminate between inherited platelet function disorder patients and healthy controls based on fibrinogen binding, similar to CRP-XL. Conclusion: Nanobody tetramers to GPVI induce platelet activation and can be used to assess the GPVI pathway in diagnostic assays.

Background During military deployment, stress regulation is vital to protect against the development of anxiety and trauma-related symptoms. Brain endocannabinoids play an important role in stress regulation and previous research has shown that genetic variations in the FAAH rs324420 polymorphism demonstrate protective effects during stress. In addition, this polymorphism shows interactions with the CRHR1 and CNR1 polymorphisms on anxiety. The present study examines whether genetic variations of the FAAH, CRHR1 and CNR1 polymorphisms interact with the development of anxiety and trauma related symptoms in military veterans. Methods Veterans (N = 949) who went on military deployment and experienced a stressful event were genotyped for FAAH rs324420, CRHR1 rs110402 and CNR1 rs2180619. Anxiety and trauma symptoms were measured pre-deployment and 6 months after deployment. Anxiety was measured with the anxiety subscale of the Symptom Checklist-90 (SCL-90) and trauma with the Self-Rating Inventory for PTSD (SRIP). Results Covariance Pattern Models demonstrated no significant relation of genetic variations in FAAH rs324420 on anxiety and PTSD symptoms from pre-deployment to 6 months after military deployment. Additionally, we investigated interactions between the FAAH s324420, CRHR1 rs110402 and CNR1 rs2180619 polymorphisms. This also demonstrated no significant effects on anxiety and PTSD symptoms pre- to post deployment. However, the covariate of childhood trauma that was included in the models was significant in all these models. Conclusion Genetic variations in FAAH rs324420 and its interactions with CRHR1 rs110402 and CNR1 rs2180619 are not related to the development of anxiety and trauma-related symptoms. The study however, indicates the importance of considering childhood trauma in the investigation of the effects of polymorphisms that are related to the endocannabinoid system on the development of anxiety and PTSD symptoms.

In an acute contact test with bees the compound of interest is dissolved in a carrier solvent (frequently acetone) and then a droplet of the solution is placed on the dorsal thorax of the bee. The volume of the droplet is standardised to 1 µL for honeybees and to 2 µL for bumblebees. In practice the same droplet volume is used for bees with very different sizes. In this research the effect of the droplet volume was evaluated with acute contact tests with dimethoate for the alfalfa leafcutter bee, the red mason bee, the honeybee and the bumblebee. The results were analysed with a ToxicoKinetic ToxicoDynamic (TKTD) model to separate kinetic from dynamic effects. This allows to compare the sensitivity of the bee based on the effect threshold and not on the time, species and test dependent LD50s. The analysis of the test results indicates that the magnitude of the response of the bees increased with increasing droplet size. The results also showed that the manifestation of effects over time is slower for the red mason bee and the bumblebee compared to the honeybee and the alfalfa leafcutter bee. This implies that the result of a 2 day test with a fixed dosing volume results in different response for a bumblebee compared to the alfalfa leafcutter bee, not because of different sensitivities of the bees involved but due to the difference of relative dosed surface ratio. So comparing the sensitivity of bee species, based on standardised tests is biased and amplifies the sensitivity for the smaller bee species.

Abstract Background Obstetrician-Gynaecologists (ObGyns) frequently face work-related adverse events such as severe obstetric complications and maternal or neonatal deaths. In 2014, the WATER-1 study showed that ObGyns are at risk of developing work-related posttraumatic stress disorder (PTSD), while many hospitals lacked a professional support system. The aim of the present study is to evaluate the current prevalence of work-related traumatic events and mental health problems among Dutch ObGyns, as well as to examine the current and desired support. Methods In 2022, an online questionnaire was sent to all members of the Dutch Society of Obstetrics and Gynaecology (NVOG), including resident and attending ObGyns. The survey included questions about experienced work-related events, current and desired coping strategies, and three validated screening questionnaires for anxiety, depression, and PTSD (HADS, TSQ, and PCL-5). Results The response rate was 18.8% and 343 questionnaires were included in the analysis. Of the respondents, 93.9% had experienced at least one work-related adverse event, 20.1% had faced a complaint from the national disciplinary board, and 49.4% had considered leaving the profession at any moment in their career. The prevalence rates of clinically relevant anxiety, depression, and psychological distress were 14.3, 4.4, and 15.7%, respectively. The prevalence of work-related PTSD was 0.9% according to DSM-IV and 1.2% according to DSM-5. More than half of the respondents (61.3%) reported the presence of a structured support protocol or approach in their department or hospital, and almost all respondents (92.6%) rated it as sufficient. Conclusions The percentages of anxiety, depression, psychological distress and PTSD are comparable to the similar study performed in 2014. Most Dutch ObGyns experience adverse events at work, which can be perceived as traumatic and, in certain cases, may lead to the development of PTSD. Structured support after adverse work-related events is now available in almost two-thirds of workplaces, and was mostly experienced as good. Despite substantial improvements in the availability and satisfaction of professional support after work-related adverse events, the prevalence rates of mental problems remain considerable, and it is imperative to sustain conversation about the mental well-being of ObGyns.

Well-preserved silicified woods are common in the Pacific Northwest, USA. Localities near the town of Post, Oregon, provide insights into the late Eocene vegetation and climate ca. 36 million years ago and data for comparing both older and younger wood floras of the region. New investigations of the late Eocene Dietz Hill locality (UF 278) revealed woods belonging to the families Pinaceae (Keteleeria farjonii sp. nov.), Cupressaceae (Taxodioxylon sp.), Magnoliaceae (Magnolia hansnooteboomii sp. nov.), Lauraceae (Laurinoxylon sp. A and B), Platanaceae (Platanoxylon haydenii (Felix) Süss and Müller-Stoll, 1977), Fabaceae (cf. Styphonolobium sp.), Fagaceae (Fagus dodgei Wheeler and Manchester, 2021, Quercus sp., Red Oak type), Juglandaceae (Carya leroyii sp. nov.), Ulmaceae (Ulmus woodii Wheeler and Manchester, 2007), Sapindaceae (Aesculus constabularisii sp. nov., Klaassenoxylon wilkinsonii gen. et sp. nov.), and Araliaceae (Plerandreoxylon oskolskii sp. nov.). Some woods could be assigned to order, but not to family, Rosales (Urticaleoxylon stevensii gen. et sp. nov., and two unnamed woods with features of  Cannabaceae and Moraceae), Sapindales (cf. Fagaroxylon sp.). There also is a Hamamelidoxylon sp., which has features found in both the Theaceae and Hamamelidaceae. These woods, together with taxa identified from co-occurring silicified fruits and seeds represent a diverse assemblage of warm temperate to subtropical woody plants, some with East Asian affinities. Comparing the wood functional traits of the Dietz Hill assemblage to the older Clarno Nut Beds (mid-Eocene) woods and to the younger woods associated with Oligocene Bridge Creek flora attests to increased seasonality and cooling climate.

The affordances of Open Educational Resources (OER) have resulted in various initiatives around the world, but most of them cease to exist once the initial project funding stops. Communities might be a means to create sustainable practices, yet, such communities can only function if their members perceive these communities as valuable. We applied the value creation framework of Wenger, Trayner, and De Laat to examine the value teachers ascribe to their engagement with an inter-institutional community on OER. In this community, 15 universities of applied sciences collaborated on sharing knowledge and resources across their institutional barriers. We collected data through user statistics, an online questionnaire, and semi-structured interviews. Major value creation occurred from teachers' personal needs, with dominant immediate and potential values. Findings on applied and realized values denote that it became easier for teachers to connect with peers, and to initiate collaboration projects across institutes. The framework we used is helpful to inform actions to further promote value creation in communities on OER. Recommendations relating to communities' aspirations, its relations with the wider organization, and adoption of OER are formulated to inform sustainable practices of inter-institutional communities.

Brokers are individuals who facilitate transfer of knowledge and resources, and coordinate efforts across boundaries of organizations. They are defined by their role rather than their organizational position. Brokers might be imperative for the formation and maintenance of inter-institutional relationship as they have the responsibility and the necessary structural position to connect otherwise separate groups. In the context of this study, brokers had the role to cultivate an inter-institutional community around open educational resources (OER) by connecting groups of teachers across higher education institutes. OER provide higher education institutes with an aid to face the challenges of improving teaching and learning. Yet most OER users encounter challenges that relate to finding resources that are relevant, up-to-date, and of good quality. Communities could minimize this issue, but many OER initiatives fizzle out as expanding their impact is an arduous task. This qualitative descriptive study draws upon cultural-historical activity theory to understand the complexities associated with the role of brokers in creating sustainable collaboration on OER across 15 higher education institutes in the Netherlands. Data was collected from project documents, process reports, reflections reports, and a retrospective focus group. The findings show that brokers engaged in a wide variety of actions but that a small-scale, personal, and content-oriented approach to encourage teachers to engage with the OER repository and the online community was perceived as the most valuable. Brokers also experienced conflicts due to the demanding context they were operating in, the ambiguity of their role, and the organizational constraints they were confronted with. Practical implications refer to supporting higher education institutes that wish to initiate sustainable collaboration across institutes.

Besides being an essential structural component of plasma membranes and the precursor of many functional compounds and signaling molecules, cholesterol was also proposed to play a role in the etiology and/or manifestation of Parkinson’s disease (PD). However, so far systematic investigations on the role of cholesterol and its metabolites present in the brain for the etiology of PD are missing. Here, we investigate for the first time the association of PD with SNPs in the genes of four cytochromes P450 (P450), CYP46A1, CYP39A1, CYP27A1 and CYP7B1, which are critical for the degradation of cholesterol in the brain. Analyzing 1,349 individuals from the PPMI data base, we found 24 SNPs in these four genes, which are significantly over- or under-represented in patients suffering from idiopathic PD (IPD). Studying each of the 362 IPD patients individually, we found that most patients (45%) showed only one associated SNP in one of the four P450 genes, while 31% displayed two associated SNPs and 18% three associated SNPs. The occurrence of some associated SNPs is in the same order of magnitude as SNPs in the GBA (beta-glucocerebrosidase) and thus might reflect a genetic predisposition for PD. As all 24 SNPs were located in introns and 3′ untranslated regions, we evaluated the prospective regulatory impact of the surrounding genomic regions by using transcriptome and epigenome data from the Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD). FOUNDIN-PD provides gene expression, open chromatin and DNA methylation data in a cohort of 89 induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons derived from people in the PPMI study. Indeed, two of the 24 SNPs, one in CYP7B1 (rs118111353) and the other one in CYP27A1 (rs74446825), were localized within a region of open chromatin in differentiated neurons. Interestingly, all iPSC lines with open chromatin in rs118111353 showed the reference allele. As all four P450, CYP46A1, CYP39A1, CYP27A1 and CYP7B1, are expressed in dopaminergic neurons, we discuss further functional studies to connect SNPs in regulatory regions with gene expression levels. Finally, potential possibilities for personalized therapeutic treatment of patients with SNPs in the four investigated P450 are discussed.

Chicán es una pequeña comunidad rural de origen maya ubicada en la península de Yucatán, conocida como “el pueblo de los sordos” por la alta prevalencia de sordera profunda. El objetivo de este estudio fue determinar el coeficiente de consanguinidad en la comunidad de Chicán utilizando el método de isonimia marital como estrategia para explicar la estructura poblacional y la alta prevalencia de sordera congénita profunda. El registro de los datos se realizó mediante encuestas a 219 individuos residentes de Chicán. Se registraron 40 apellidos diferentes, de ellos 30 son de origen maya. El 23,3% de la muestra presentó apellidos isonímicos, siendo Collí (94,1%) el más frecuente. La consanguinidad total observada fue de 0,0585, mientras que el componente aleatorio (Fr = 0,0571) fue 38 veces mayor que el componente no aleatorio (Fn = 0,0015). Se registraron 18 personas con sordera congénita profunda, de las cuales 11 fueron isonímicas para el apellido Collí. Los resultados indican que las uniones consanguíneas en Chicán se deben principalmente al pequeño tamaño de la población y a su relativo aislamiento. La alta prevalencia de sordera profunda en Chicán puede ser consecuencia de la consanguinidad, la cual predispone a la aparición de trastornos hereditarios recesivos.

Background and purpose: Chronic postsurgical pain after total knee arthroplasty (TKA) is frequent and may be reduced by pain neuroscience education (PNE), teaching people about pain from a neurobiological perspective. This study investigated primarily the effectiveness of 2 individual sessions of PNE versus usual care on pain levels 3 months postoperatively in patients undergoing TKA. Secondary outcomes were physical functioning, stiffness, health-related quality of life, pain catastrophizing, attention to pain, and levels of anxiety and depression. Methods: A prospective single-center, parallel-group randomized controlled trial was undertaken including patients aged 18 years or older scheduled for primary TKA. 68 patients were randomly assigned to PNE or usual care. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score 3 months postoperatively. Outcomes were measured preoperatively, at 2 weeks (acute phase), and at 3 and 12 months postoperatively. Results: We found no statistically significant difference (0.4 points; 95% confidence interval [CI] –1.7 to 2.4) in WOMAC pain scores 3 months after TKA between the PNE and control group. We found a statistically significant difference between the 2 groups for attention to pain at 3 months in favor of PNE (P = 0.02). Conclusion: This RCT showed that PNE was not superior to usual care in terms of reducing pain at 3 months after TKA. Attention to pain, as a secondary outcome, was significantly lower in the PNE group compared with usual care. Other secondary outcome measures showed no significant differences.

Background: Malignant pleural mesothelioma (MPM) is a rare thoracic malignancy with poor prognosis and limited treatment options. Immunotherapy shows potential for improved outcomes; however, real-world evidence on its use will take time to accumulate. This study examined patient characteristics, treatment patterns, overall survival (OS), and predictors of mortality among patients diagnosed with MPM in Denmark prior to the introduction of newer treatments. Methods: This historical cohort study based on routinely collected Danish National Registry data included adults newly diagnosed with MPM between 01 January 2011 and 31 May 2018. Summary statistics were used to describe patient characteristics and initial treatment. OS was estimated using Kaplan-Meier methods; Cox regression was used to compare patient mortality against the (age/sex-matched) general population and to investigate mortality predictors. Results: Overall, 880 patients were included; 44% had advanced MPM, 37% had non-advanced MPM, and 19% had unknown MPM stage. Median age at diagnosis was 71.9 years, and 82% of the patients were male. Within 180 days of diagnosis, no treatment was recorded for 215 patients (54%) with advanced MPM and 150 (46%) with non-advanced MPM. Median time-to-initial treatment (interquartile range) was 47 days (31–111) overall, 40 days (28–77) in patients with advanced MPM, and 53 days (35–121) with non-advanced MPM. Median OS was 13.7 months overall (non-advanced MPM: 18.0 months vs. advanced MPM: 10.0 months). Predictors of higher mortality were older age at diagnosis, histology, and advanced MPM stage. Interpretation: These findings provide a baseline upon which to evaluate MPM epidemiology as newer treatments are adopted in routine practice.

Despite decades of extensive research on creativity, the field still combats psychometric problems when measuring individual differences in creative ability and people's potential to achieve real-world outcomes that are both original and useful. We think these seemingly technical issues have a conceptual origin. We therefore propose a minimal theory of creative ability (MTCA) to create a consistent conceptual theory to guide investigations of individual differences in creative ability. Building on robust theories and findings in creativity and individual differences research, our theory argues that creative ability, at a minimum, must include two facets: intelligence and expertise. So, the MTCA simply claims that whenever we do something creative, we use most of our cognitive abilities combined with relevant expertise to be creative. MTCA has important implications for creativity theory, measurement, and practice. However, the MTCA is not necessarily true; it is a minimal theory. We discuss and reject several objections to the MTCA.