Pharmaco-invasive strategy and dosing of tenecteplase in STEMI patients 60 to <75 years: An inter-trial comparison of the STREAM-1 and STREAM-2 trials

Background Previous studies indicate a safety risk with full-dose TNK in elderly patients. In a study of patients >= 60 years STREAM-2 (STrategic Reperfusion Early After Myocardial infarction-2), a pharmaco-invasive (PI) strategy with half-dose TNK was similar (in efficacy and safety) to primary percutaneous coronary intervention (PPCI) in ST-elevation myocardial infarction (STEMI) patients presenting = 50% (71.2% vs 68.7%, P = . 519): their ICH risks were 2.1% vs 1.5%, P = . 605 respectively). Following angiography, PI patients had nominally better ST resolution >= 50% compared to their PPCI counterpart (STREAM-1: 87.7% vs. 83.2%, P = . 120; STREAM-2: 88.2% vs. 81.0%, P = . 048) with similar primary composite outcome at 30 days (STREAM-1: 14.4% vs. 16.3%, 0.90 [0.62, 1.31]; STREAM-2: 9.0% vs 8.1%, 1.29 [0.64, 2.61]). Major (nonICH) bleeding markedly declined in STREAM-2 compared to STREAM-1 in both treatment groups (STREAM-1: 7.1%vs. 6.0%; STREAM-2: 0.3% vs. 0.7%). Conclusions In STEMI patients 60 to < 75 years presenting within 3 hours of symptoms, half-dose PI treatment appears as efficacious as a full-dose PI strategy with a low systemic bleeding risk. Half-dose PI treatment deserves consideration when timely PPCI is not attainable in this important STEMI sub-group. Clinicaltrials.gov registration numbers NCT00623623, NCT02777580.Funding This investigator-initiated trial received funding from the Department of Research and Development of KU Leuven, Life Science Research Partners, and Boehringer Ingelheim. Acknowledgments The authors gratefully acknowledge Dr. Leiah Luoma, PhD and Lisa Soulard for providing editorial assistance

Schema Matching with Large Language Models: an Experimental Study

Large Language Models (LLMs) have shown useful applications in a variety of tasks, including data wrangling. In this paper, we investigate the use of an off-the-shelf LLM for schema matching. Our objective is to identify semantic correspondences between elements of two relational schemas using only names and descriptions. Using a newly created benchmark from the health domain, we propose different so-called task scopes. These are methods for prompting the LLM to do schema matching, which vary in the amount of context information contained in the prompt. Using these task scopes we compare LLM-based schema matching against a string similarity baseline, investigating matching quality, verification effort, decisiveness, and complementarity of the approaches. We find that matching quality suffers from a lack of context information, but also from providing too much context information. In general, using newer LLM versions increases decisiveness. We identify task scopes that have acceptable verification effort and succeed in identifying a significant number of true semantic matches. Our study shows that LLMs have potential in bootstrapping the schema matching process and are able to assist data engineers in speeding up this task solely based on schema element names and descriptions without the need for data instances.S. Vansummeren was supported by the Bijzonder Onderzoeksfonds (BOF) of Hasselt University under Grant No. BOF20ZAP02. This research received funding from the Flemish Government under the “Onderzoeksprogramma Artificiële Intelligentie (AI) Vlaanderen” programme. This work was supported by Research Foundation—Flanders(FWO)forELIXIRBelgium(I002819N).Theresources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research FoundationFlanders (FWO) and the Flemish Government

Is Intravenous and Oral Topotecan in Small-Cell Lung Cancer Truly Equal? A Case Report

Introduction: Treatment with topotecan is standard-of-care therapy for relapsed small-cell lung cancer (SCLC). Both oral and intravenous administrations of topotecan have been extensively researched and are found to be equally effective with less adverse events in the oral group. Case Presentation: We report a case of a patient with SCLC, who had previously received oral topotecan, with radiological stable disease with no changes in tumor or metastasis diameter size after two administrations. Subsequently, this patient received intravenous topotecan instead of oral due to supply difficulties. After one administration of intravenous topotecan, we saw significant disease regression. Conclusion: This is to our knowledge the first reported case of better response of intravenous topotecan than oral topotecan. Multiple extrinsic (e.g., food, medication) factors were investigated but could not deliver an explanation

Deconstructing Binaries: Demolition and the limits of reuse

Contemporary architectural practice – in Western Europe at least – is by necessity moving away from previously dominant, tabula rasa models of demolition and reconstruction, towards approaches based on the care, repair and transformation of existing buildings. In this transition, it is important not to fall into the trap of viewing practices of adaptive reuse through the reductive lens of a preservation/demolition binary. If anything, reuse projects call precisely such ‘either/or’ binary oppositions into question, deconstructing absolute dualities like past/future, old/new, and finished/open-ended to create spaces characterised by hybridity and ambiguity. Likewise, “Ne jamais démolir”, a manifesto for reuse as an ecologically and socially sustainable alternative to wholesale demolition, does not aim to rule out or preclude localised acts of surgical demolition that contribute to maintaining, transforming and extending the life of a building. On the contrary, Lacaton & Vassal insist that nothing should prevent the architect from “‘doing just what is needed’. In other words, what is essential for the project”. Determining exactly what is needed most often relies not on one single, overarching strategy, but on a whole series of decisions linked to specific architectural interventions or gestures that combine to realise the project. Like all architecture, projects of adaptive reuse are dictated and shaped by an array of limiting factors. Some – such as financial or legislative constraints – fluctuate over time and can therefore be more easily navigated. Others are more structural: for example, the buildings currently most threatened with destruction are those built during the last 50 years, since neoliberal maximisation of profit at any cost has seen floor areas and ceiling heights become much less generous and therefore less easily adaptable. Targeted approaches of partial demolition and deconstruction offer a way to transgress both physical and nonmaterial limits by permitting the investigation, unlocking and resetting of spaces without resorting to wholesale demolition. Such operations face their own set of challenges: on one hand, heritage concerns that insist on preservation over adaptation impose an stranglehold on buildings that could otherwise find a new lease of life through critical and careful interventions. At the other extreme, valid questions should be raised regarding how much original fabric can be demolished and removed before a building ceases to be a project of reuse but in essence represents a new construction. Furthermore, deeply-ingrained, narrow societal expectations of what constitutes ‘new’ or ‘finished’ architecture often mean experimental projects featuring hybrid constructions or material juxtapositions are resisted and even rejected on aesthetic grounds. This paper examines the extent to which the preservation/demolition binary represents a false dichotomy that hinders adaptive reuse by unnecessarily limiting the options available to practitioners. It draws on current research undertaken as part of the PhD project Adapt, Reuse, a hybrid, embodied practice of reuse that engages equally with theory and practice in a reciprocal relay. Combining first-hand experience, conversations with practitioners and critical analysis of selected built projects, the paper investigates the work of a number of practices whose creative demolitions trace and identify the limits of reuse in order to test how they might be pushed further. This ongoing research focuses on reference cases at the scale of the architectural intervention rather than at the scale of the project, as a way of identifying approaches, attitudes or gestures that taken together might suggest and enable the development of a wider conceptual framework for adaptive reuse

Polymer dynamics under tension: mean first passage time for looping

This study deals with polymer looping, an important process in many chemical and biological systems. We investigate basic questions on the looping dynamics of a polymer under tension using the freely-jointed chain (FJC) model. Previous theoretical approaches to polymer looping under tension have relied on barrier escape methods, which assume local equilibrium, an assumption that may not always hold. As a starting point we use an analytical expression for the equilibrium looping probability as a function of the number of monomers and applied force, predicting an inverse relationship between looping time and looping probability. Using molecular dynamics simulations the predictions of this theoretical approach are validated within the numerical precision achieved. We compare our predictions to those of the barrier escape approach, by way of a calculation of the mean first passage time (MFPT) for the ends of a polymer to cross. For this purpose, we derive the exact free energy landscape, but resulting temporal predictions do not agree with the observed inverse scaling. We conclude that the traditional barrier escape approach does not provide satisfactory predictions for polymer looping dynamics and that the inverse scaling with looping probability offers a more reliable alternative

Exploring Expert Behavior of Process Mining Analysts

Within the field of Process Mining, the research topic known as Process of Process Mining emerged. Process of Process Mining seeks to comprehend process mining analysts' thought processes and behavioral patterns. A better understanding of the analysts' behavior allows for the design of more effective process mining tools and the construction of more efficient process mining training. The behavioral differences between expert and non-expert process mining analysts have not yet been studied within this domain. Therefore, my PhD research aims to conceptualize behavior in Process of Process Mining research and identify expertise-related behavioral differences among process mining analysts

Review of European Guidelines on Palliative Sedation: A Foundation for the Updating of the European Association for Palliative Care Framework

In 2009, the European Association for Palliative Care (EAPC) developed a framework on palliative sedation, acknowledging this practice as an important and ethically acceptable intervention of last resort for terminally ill patients experiencing refractory symptoms. Before and after that, other guidelines on palliative sedation have been developed in Europe with variations in terminology and concepts. As part of the Palliative Sedation project (Horizon 2020 Funding No. 825700), a revision of the EAPC framework is planned. The aim of this article is to analyze the most frequently used palliative sedation guidelines as reported by experts from eight European countries to inform the discussion of the new framework. The three most reported documents per country were identified through an online survey among 124 clinical experts in December 2019. Those meeting guideline criteria were selected. Their content was assessed against the EAPC framework on palliative sedation. The quality of their methodology was evaluated with the Appraisal Guideline Research and Evaluation (AGREE) II instrument. Nine guidelines were included. All recognize palliative sedation as a last-resort treatment for refractory symptoms, but the criterion of refractoriness remains a matter of debate. Most guidelines recognize psychological or existential distress as (part of) an indication and some make specific recommendations for such cases. All agree that the assessment should be multiprofessional, but they diverge on the expertise required by the attending physician/team. Regarding decisions on hydration and nutrition, it is proposed that these should be independent of those for palliative sedation, but there is no clear consensus on the decision-making process. Several weaknesses were highlighted, particularly in areas of rigor of development and applicability. Theidentified points of debate and methodological weaknesses should be considered in any update or revision of theguidelines analyzed to improve the quality of their content and the applicability of their recommendations

The role of the exposome in biological ageing and appetite regulation across youth - The relation of the external exposome with telomeres and appetite hormones

Noncommunicable diseases (NCDs) are chronic conditions that are not directly transmissible between individuals (e.g. cancers, cardiovascular diseases, obesity, diabetes type 2). These diseases represent a major global health burden as they significantly contribute to mortality worldwide, causing 41 million deaths each year. NCDs emerge from a complex interplay between the individual’s genetic predisposition, surrounding environment (e.g. work and living conditions) and personal lifestyle choices (e.g. smoking, diet, physical activity). However, the exact underlying mechanisms remain to be explored. While genetic makeup is fixed, environmental and lifestyle factors are modifiable, offering opportunities for intervention. To address these modifiable contributors, the concept of the exposome has been developed, encompassing the totality of environmental exposures throughout an individual's life, starting from conception. While previous research has largely focused on the effects of single exposures or lifestyle factors on disease development, the exposome opens opportunities for understanding the interplay between exposures, their combined effects, and the underlying mechanisms which are crucial for effective prevention. Although most research has focused on adults’ lifestyle and exposures, early life may represent a critical period for the onset of NCDs, underscoring the need to investigate early-life mechanisms and exposures. This dissertation aims to tackle these knowledge gaps by focusing on two potential underlying mechanisms (biological ageing and appetite regulation) through which the exposome may contribute to the early-life development of NCDs using population-based research. As many NCDs are linked with ageing, this dissertation investigates the link between the exposome and telomere attrition, a biomarker for biological ageing. Shorter telomeres have been linked to several NCDs, providing valuable insight into early biological effects and offering an ideal model to study the exposome's impact on ageing from early life onward. The second focus of this dissertation is on exploring underlying mechanisms of obesity, which is not only an NCD in itself but also a significant risk factor for the development of other NCDs, effectively acting as a double burden. Since obesity is often linked to increased appetite and impaired appetite hormone levels, this work explores appetite regulation as an underlying mechanism. It pioneers research concerning the exposome's impact on appetite-regulating hormones during childhood and the prenatal period, specifically focusing on ghrelin, leptin, peptide yy, glucagon-like-peptide 1 and pancreatic polypeptide. This dissertation includes population-based research that was performed using the data of two Flemish cohorts, a birth cohort ENVIRONAGE (ENVIRonmental influence ON early AGEing) and a child/adolescent cohort IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS). In both cohorts data was collected on multiple exposures of the children and newborns. These exposures, could be combined by creating a multi-exposure score reflecting the exposome of the children, to assess the overall effect of a combination of exposures towards both outcomes, telomere attrition and appetite hormones. The original research findings are presented in two parts (Part II–III). In Part II the relation between the exposome and telomere attrition is assessed in children (2–10 years old at baseline) (Chapter 1). Part III shifts focus to appetite regulation and its link to the exposome. Chapter 2 explores the relationship between the exposome and appetite-regulating hormones in children and adolescents (aged 4–16 years). Chapter 3 investigates the health relevance of appetite hormones in cord blood by examining their associations with early-life growth trajectories and body composition, key risk factors for later obesity. Chapter 4 assesses the influence of prenatal exposures on cord blood appetite hormone levels. In summary, we observed that a combination of a healthy lifestyle and a green environment is associated with reduced telomere attrition over 5 to 7 years in childhood. Specifically, exposure to residential green space, particularly vegetation taller than 3 meters, was linked to slower telomere shortening, with part of this association mediated by smaller waist circumference. Environmental exposures at study (i.e. air pollution and residential green space), were also associated with fasting appetite hormone levels in children, potentially contributing to obesity development early in life. Similarly, prenatal exposure to air pollution was found to influence appetite hormone levels in cord blood. Interestingly, these cord blood appetite hormone levels were associated with postnatal growth trajectories and body composition. Collectively, these results highlight that the exposome influences internal processes related to biological ageing and appetite regulation as early as the prenatal and childhood periods. This dissertation strengthens the existing literature on how lifestyle factors and environmental exposures are linked to biological processes, emphasizing that both lifestyle and environmental factors play critical roles in health starting from conception. It also provides new insights, particularly into the relationship between the exposome and appetite hormones early in life, and is the first to show associations between specific cord blood appetite hormones and postnatal growth and body composition. Therefore, this work can serve as a starting point for further exploration of appetite hormones, telomeres, and their potential contribution to the development of NCDs. Future research should verify these results in other (larger) study populations, especially populations with a higher obesity prevalence and lower socio-economic status. Experimental studies are necessary to establish causality of the observed associations. Finally, methodological improvements are suggested to minimize bias. From a public health perspective, this dissertation underscores the importance of early-life interventions targeting both lifestyle and environmental factors to reduce the risk of NCDs. By linking the exposome to biological ageing and appetite regulation, this work contributes to the growing body of evidence advocating for preventive strategies to address the NCD burden, particularly the obesity crisis, from an early age onwards. Ultimately, the research conducted in this dissertation emphasizes prevention as the cornerstone for sustainable health improvements, aligning with the adage: "Prevention is better than cure