Early Phase Research Articles

Abstract 1302: Development and implementation of a systematic approach to measure patient-reported outcomes in early-phase cancer trials

Abstract Background: There has been a shift in the clinical trial landscape toward early-phase studies where data from well-designed and pivotal phase I/II trials is leading to accelerated drug approval. Our goal was to develop a standardized approach to the measurement and reporting of patient-reported outcomes (PROs) in early-phase trials to improve assessment of tolerability, address noted barriers to inclusion, and enhance patient-provider communication to inform treatment decisions and ultimately improve outcomes. Methods: The Office of Patient Centered Outcomes Research (OPCORe) was established in 2022 within the Center for Cancer Research at the National Cancer Institute (NCI) with the mission to advance understanding of the clinical benefit and tolerability of cancer therapies by integrating patient-centered approaches into CCR clinical trials by fostering education and collaboration with stakeholders. Implementation of regulatory/consortia guidelines related to use of core constructs, assessment frequency, and hypothesis-driven objectives and analysis plans through protocol template, development of data capture, email-based alerts and data visualization for clinical providers was developed and standardized templates for protocol language, research staff education, tools for workflow, and tracking implemented. Results: The OPCORe protocol template includes measurement of 3 constructs, including tolerability, clinical benefit and disease-specific impact, as well as anchors of meaningful change. Core symptomatic toxicities are measured to inform understanding across trials with agent/class-specific symptomatic toxicities added to assure relevance. Baseline and standardized weekly electronic capture of tolerability during early cycles with alerts to clinical research staff if moderate-severe toxicities reported helps facilitate patient check-ins. Repeat PROs assessments in later cycles are expanded to include disease-specific assessments and align with disease evaluation to further inform clinical impact. To date, we have collaborated with 7 research groups and developed approaches for first-in-human, phase I, and phase II studies with trial start-up and data collection in process. Conclusion: The value of including PROs in cancer trials is increasingly recognized by regulators, clinicians, patients, and advocates to advance understanding of the clinical benefit & tolerability of emerging therapies. Standardization and incorporation of PROs in earlier phase trials may enable PROs to be optimized, improve later phase trial design, and help inform health policy, support drug approval, and promote shared decision making between providers and patients to inform treatment decisions. Citation Format: Amanda L. King, Jason E. Levine, Elizabeth Vera, Yuti Gandhi, Elaine Novakovich, Theresa Yu, Sefanit Berhanu, Ciara Locke, Kaelyn Julmeus, Tito Mendoza, Terri S. Armstrong. Development and implementation of a systematic approach to measure patient-reported outcomes in early-phase cancer trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1302.

Pandemic phase-related racial and ethnic disparities in COVID-19 positivity and outcomes among patients presenting to emergency departments during the first two pandemic waves in the USA

BackgroundIn many countries including the USA, the UK and Canada, the impact of COVID-19 on people of colour has been disproportionately high but examination of disparities in patients presenting to...

Spread of awareness of COVID-19 between December 2019 and March 2020 in France

During the early phase of outbreaks, awareness of the presence of the disease plays an important role in transmission dynamics. To investigate the processes of how people become aware of a disease, we conducted two complementary investigations. First, we surveyed 868 academic researchers in France, on the time and circumstances when they became aware of COVID-19 as an important event. We found that 25% did so before February 18th (first death in France), 50% did so before March 10th (first presidential allocution) and 75% did so before March 16th (announcement of the lockdown). Awareness came from nine categories of circumstances: (1) decisions taken by the government (elicited by 35.7% participants); (2) information from media or social media (24.7%); (3) conversation with friends (22.4%); (4) observed changes in their personal lives (14.0%); (5) decisions taken by the employer (9.2%); (6) observed changes at work (9.9%); (7) suspected case of COVID-19 in their entourage (3.1%); (8) fear for oneself or their entourage (2.8%) and (9) self-appraisal of scientific reports (2.8%). Second, we appraised three general media in France (a television news show, a radio news show, and a newspaper) and showed that COVID-19 became a preeminent topic only after March 1st 2020 when the epidemic is present on national soil. Our results show that multiple intricated factors prompt the awareness of an emerging infectious disease. Awareness is not solely driven by general media as they begin to focus on the topic late.

Centering artist voices: notes from a survey of artists and cultural workers in Philadelphia, PA, and Richmond, VA

ABSTRACT This essay explores our work collecting artist experiences and attending to the voices of artists themselves in two US cities. Prompted by an earlier phase of focus group research in Philadelphia with artists who voiced their needs as workers, we undertook a survey of working artists in Philadelphia and Richmond, Virginia. This survey research asks about the spatial patterns of artists living, working, and presentation locations and how that geography has changed over time, as well as how artists have weathered the pandemic in two cities. We believe this study makes innovative contributions from a methodological standpoint, given the questions we asked that supported a spatial analysis of where artists live, work, and present their work. It is also an engaged process where we centered long-neglected voices through focus groups and surveys. It is an exploration of how artists engage with space and time.

Early Validation and Verification of System Behaviour in Model-based Systems Engineering: A Systematic Literature Review

In the Systems Engineering (SE) domain there has been a paradigm shift from document-based to model-based system development artefacts; in fact, new methodologies are emerging to meet the increasing complexity of current systems and the corresponding growing need of digital workflows. In this regard, Model-Based Systems Engineering (MBSE) is considered as a key enabler by many central players of the SE community. MBSE has reached an adequate level of maturity, and there exist documented success stories in its adoption in industry. In particular, one significant benefit of utilising MBSE when compared to the traditional manual and document-centric workflows is that models are available from early phases of systems development; these enable a multitude of analyses prior any implementation effort together with other relevant capabilities, like the automation of development tasks. Nonetheless, it is noticeable there is a lack of a common understanding for how formal analyses for the verification and validation (V&V) of systems behaviour, specifically in the early phases of development, could be placed in an MBSE setting. In this article, we report on the planning, execution, and results of a systematic literature review regarding the early V&V of systems behaviour in the context of model-based systems engineering. The review aims to provide a structured representation of the state of the art with respect to motivations, proposed solutions, and limitations. From an initial set of potentially relevant 701 peer-reviewed publications we selected 149 primary studies, which we analysed according to a rigorous data extraction, analysis, and synthesis process. Based on our results, early V&V has usually the goal of checking the quality of a system design to avoid discovering flaws when parts are being concretely realised; SysML is a de facto standard for describing the system under study, while the solutions for the analyses tend to be varied; also V&V analyses tend to target varied properties with a slight predominance of functional concerns, and following the variation mentioned so far the proposed solutions are largely context specific; the proposed approaches are usually presented without explicit limitations, while when limitations are discussed, readiness of the solutions, handling of analyses simplifications/assumptions, and languages/tools integration are among the most frequently mentioned issues. Based on the survey results and the standard SE practices, we discuss how the current state-of-the-art MBSE supports early V&V of systems behaviour with a special focus on industrial adoption and identify relevant challenges to be researched further.

Enhancing the Coupling of Real-Virtual Prototypes: A Method for Latency Compensation

Currently, innovations in mechatronic products often occur at the system level, requiring consideration of component interactions throughout the entire development process. In the earlier phases of development, this is accomplished by coupling virtual prototypes such as simulation models. As the development progresses and real prototypes of certain system components become available, real-virtual prototypes (RVPs) are established with the help of network communication. However, network effects—all of which can be interpreted as latencies in simplified terms—distort the system behavior of RVPs. To reduce these distortions, we propose a coupling method for RVPs that compensates for latencies. We present an easily applicable approach by introducing a generic coupling algorithm based on error space extrapolation. Furthermore, we enable online learning by transforming coupling algorithms into feedforward neural networks. Additionally, we conduct a frequency domain analysis to assess the impact of coupling faults and algorithms on the system behavior of RVPs and derive a method for optimally designing coupling algorithms. To demonstrate the effectiveness of the coupling method, we apply it to a hybrid vehicle that is productively used as an RVP in the industry. We show that the optimally designed and trained coupling algorithm significantly improves the credibility of the RVP.

Video-mediated collaborative lesson planning in virtual exchange among transnational teams of pre-service language teachers

AbstractVirtual exchange (VE) projects in pre-service language teacher education are increasingly being recognized as an innovative practice due to their affordances for providing teacher learning opportunities in technology-rich environments. This study aims to report these opportunities based on results from a VE project consisting of diverse teacher education activities, including lectures, webinars, asynchronous tasks, and synchronous video-mediated interactions. This project provides a medium for pre-service teachers to collaboratively design a lesson to be implemented in hybrid language learning environments. We specifically deal with the video-mediated interactions of the transnational groups of pre-service language teachers using multimodal conversation analysis (CA) as the research methodology and investigate VE phases to explore how their interactions become consequential for the final pedagogical design. The findings show that the pre-service teachers retrospectively orient to shared practices in the earlier phases of the VE project, and the deployment of retrospective orientation as an interactional resource creates interactional space for collaborative decision-making related to their pedagogical designs. We argue that tracking the video-mediated pedagogical interactions of the pre-service teachers using CA is a methodological innovation that allows researchers to collect interactional evidence for the emergent teacher learning opportunities. The findings bring new insights to the role of the technology-mediated settings (e.g. VEs and telecollaboration) in language learning, teaching, and teacher education and in bridging different cultures, curricula, and physical spaces.

Feasibility of wastewater-based detection of emergent pandemics through a global network of airports.

Wastewater-based surveillance has been put into practice during the pandemic. Persistence of SARS-CoV-2 in faeces of infected individuals, and high volume of passengers travelling by air, make it possible to detect virus from aircraft wastewater, lending itself to the potential identification of a novel pathogen prior to clinical diagnosis. In this study, we estimated the likelihood of detecting the virus through aircraft wastewater from the probabilities of air travel, viral shedding, defecation, testing sensitivity, and sampling. We considered various hypothetical scenarios, with diverse sampling proportions of inbound flights, surveillance airports, and sources of outbreaks. Our calculations showed that the probability of detecting SARS-CoV-2 would increase exponentially against time in the early phase of the pandemic, and would be much higher if the 20 major airports in Asia, Europe, and North America cooperated to perform aircraft wastewater surveillance. We also found other contributors to early detection, including high sampling proportion of inbound flight at destination airports, small population size of the epicentre relative to the travel volume, and large volume of outbound travelers to major airports around the globe. We concluded that routine aircraft wastewater monitoring could be a feasible approach for early identification and tracking of an emerging pathogen with high faecal shedding rates, particularly when implemented through a global surveillance network of major airports.

Research on Optimal Cooling Landscape Combination and Configuration Based on Local Climate Zones—Fuzhou, China

The deterioration of the urban thermal environment has seriously affected the quality of life of urban residents, and studying the optimal cooling landscape combination and configuration based on local climate zones (LCZs) is crucial for mitigating the thermal environment. In this study, the LCZ system was combined to analyze the spatial and temporal changes to the thermal environment in the central area of Fuzhou, and the 159 blocks in the core area were selected to derive the optimal LCZ combination and configuration. The conclusions are as follows: (1) From 2013 to 2021, the building layout of the study area became more open and the building height gradually increased. The high-temperature areas were mainly clustered in the core area; (2) The LSTs for low-rise buildings (LCZ 3 (41.67 °C), LCZ 7 (40.10 °C), LCZ 8 (42.61 °C), and LCZ 10 (41.85 °C)) were higher than the LSTs for high-rise buildings (LCZ 1 (38.58 °C) and LCZ 4 (38.50 °C)); (3) The thermal contribution index for low building types was higher for dense buildings (LCZ 3 (0.4331), LCZ 8 (0.3149), and LCZ 10 (0.2325)) than for open buildings (LCZ 6 (0.0247) and LCZ 9 (0.0317)); (4) Blocks with an average LST of 36 °C had the most cost-effective cooling, and the combination and configuration of LCZs within such blocks were optimal. Our results can be used to better guide urban planners in managing LCZ combinations and configurations within blocks (the smallest planning unit) at an earlier phase of thermal environment design, and for appropriately adapting existing block layouts, providing a new perspective on urban thermal environment research with important implications for climate-friendly city and neighborhood planning.

National Bureau of Investigation: Towards Mitigating Women and Children Trafficking and Exploitation

The Philippines is one of the most trafficked countries. The Philippines is considered to be one of the most prominent online platforms for child sexual exploitation. This study will only focus on the aftercare services during the rescue and early recovery phase of the woman and child victims in violation of RA 9208- Anti-Trafficking in Persons Act of 2003, as amended RA 10364-Expanded Anti-Trafficking Act in Persons Act of 2012. It will not discuss the reintegration phase for it is the scope of social work and development (DSWD). Currently, there is no figure for the actual number of trafficking for there are unreported cases and it is borderless. There are also limitations in terms of women NBI agents. Rescue operations are beyond the scope of this paper for it is classified information and it varies from one operation to another. Mitigating the trafficking of women and children begins with addressing the root causes, raising public awareness, and strengthening the task forces that deal with these cases. According to the United Nations and the U.S. State Government, there are 3Ps to mitigate trafficking in persons. The researcher found 4Ps and these are: Prevent, Protect, Prosecute, and Partnership. The fight against trafficking in human beings in the Philippines remains an urgent and multifaceted challenge that requires a holistic and multi-pronged approach. Government, law enforcement, civil society, and international allies have played a key role in increasing awareness, enacting more stringent legislation, and supporting victims. Keywords: trafficking, exploitation, aftercare services, recue and early recovery phase, multi-pronged approach, women and children

A mathematical model to assess the effectiveness of test-trace-isolate-and-quarantine under limited capacities.

Diagnostic testing followed by isolation of identified cases with subsequent tracing and quarantine of close contacts-often referred to as test-trace-isolate-and-quarantine (TTIQ) strategy-is one of the cornerstone measures of infectious disease control. The COVID-19 pandemic has highlighted that an appropriate response to outbreaks of infectious diseases requires a firm understanding of the effectiveness of such containment strategies. To this end, mathematical models provide a promising tool. In this work, we present a delay differential equation model of TTIQ interventions for infectious disease control. Our model incorporates the assumption of limited TTIQ capacities, providing insights into the reduced effectiveness of testing and tracing in high prevalence scenarios. In addition, we account for potential transmission during the early phase of an infection, including presymptomatic transmission, which may be particularly adverse to a TTIQ based control. Our numerical experiments inspired by the early spread of COVID-19 in Germany demonstrate the effectiveness of TTIQ in a scenario where immunity within the population is low and pharmaceutical interventions are absent, which is representative of a typical situation during the (re-)emergence of infectious diseases for which therapeutic drugs or vaccines are not yet available. Stability and sensitivity analyses reveal both disease-dependent and disease-independent factors that impede or enhance the success of TTIQ. Studying the diminishing impact of TTIQ along simulations of an epidemic wave, we highlight consequences for intervention strategies.

5-Hydroxytryptophan acts as a gap junction inhibitor to limit the spread of chemotherapy-induced cardiomyocyte injury and mitochondrial dysfunction.

Anthracycline chemotherapeutics like doxorubicin (DOX) are widely used against various cancers but are accompanied by severe cardiotoxic effects that can lead to heart failure. Through whole transcriptome sequencing and pathological tissue analysis in a murine model, our study has revealed that DOX impairs collagen expression in the early phase, causing extracellular matrix anomalies that weaken the mechanical integrity of the heart. This results in ventricular wall thinning and dilation, exacerbating cardiac dysfunction. In this work, we have identified 5-hydroxytryptophan (5-HTP) as a potent inhibitor of gap junction communication. This inhibition is key to limiting the spread of DOX-induced cardiotoxicity. Treatment with 5-HTP effectively countered the adverse effects of DOX on the heart, preserving ventricular structure and ejection fraction. Moreover, 5-HTP enhanced mitochondrial respiratory function, as shown by the O2k mitochondrial function assay, by improving mitochondrial complex activity and ATP production. Importantly, the cardioprotective benefits of 5-HTP did not interfere with DOX's ability to combat cancer. These findings shed light on the cardiotoxic mechanisms of DOX and suggest that 5-HTP could be a viable strategy to prevent heart damage during chemotherapy, offering a foundation for future clinical development. This research opens the door for 5-HTP to be considered a dual-purpose agent that can protect the heart without compromising the oncological efficacy of anthracycline chemotherapy.

Correlation between Pre-Operative Myocardial Fibrosis and Early Post CABG Dysrhythmia

Background: Cardiac magnetic resonance (CMR) imaging combines the assessment of both the functional and structural aspects of the heart in order to identify the existence, timing, and intensity of ischemic heart disease by analyzing the function of the myocardium and the movement of the heart wall. This study aimed to investigate whether preoperative myocardial fibrosis, measured by CMR imaging, may be used to predict the incidence of rhythm disturbances in the early postoperative phase after coronary artery bypass grafting (CABG) surgery.
 Methods: Two groups of 92 patients who had CABG procedures performed were studied in this retrospective observational single site cohort study: There were 43 patients in Group A who had atrial or ventricular arrhythmia, and 49 patients in Group B who did not.
 Results: There was no correlation between arrhythmia and non-arrhythmia group and age, sex, body mass index, risk factor, CMR timing before surgery, cross clamp time, bypass time, left ventricular end-diastolic volume index (LV EDVI), LV end-systolic volume index (ESVI), stroke volume index (SVI), LV ejection fraction (EF) and territory of scar and were positive correlation between both groups and scar (P <0.001). Scar% was an independent predictor of occurrence of rhythm disturbance (P=0.002) while LV EDVI, LV EF, LV ESVI, SVI, and presence of scar were not. Group A had a statistically significantly lower LV-EF% and lower LV-SVI compared to Group B. Group A had a higher scar percentage compared with group B and this was statistically significant (P <0.001). Rhythm disturbance occurred more often in patients with a scar percentage >14.8% {P=0.0002 and area under ROC curve (AUC)=0.708}.
 Conclusions: CMR has evolved as a gold standard non-invasive imaging tool in cardiovascular medicine. Preoperative CMR imaging may be a promising tool for predicting postoperative cardiac arrhythmia after CABG. Our study showed that preoperative myocardial scarring >14.8%, as determined by CMR imaging, was predictive of early postoperative arrhythmia in patients undergoing CABG.

Chemical weathering along a one-million-year soil age gradient on the Galápagos Islands

The Galápagos archipelago, a chain of islands formed by hotspot-induced volcanism on the Nazca tectonic plate, exhibits pronounced gradients of rock age and climate. Here, we investigate chemical weathering along a soil chronosequence (1.5 to 1070 ka) and under humid vs. dry conditions. Our results show considerable loss of base cations already in the early to intermediate phases of weathering under humid conditions (e.g. 95 % of Na and 78 % of Mg lost from the topsoil after 26 ka) and almost complete loss from the entire profile in soils older than 800 ka. Depletion of Si was less pronounced, with topsoil losses of 24 % and 63–68 % after 26 ka and >800 ka, respectively. Under dry conditions, weathering rates were much lower, e.g. 33 % of Na and 1.4 % of Mg lost from the topsoil after 26 ka. Indices of chemical weathering, e.g. the Chemical Index of Alteration and the Ruxton Ratio, correlated well with indicators of pedogenic development, such as solum thickness, soil pH, or the ratio of oxalate- to dithionite-extractable Fe. Total weathering flux and associated CO2 consumption rates estimated from profile-scale element losses in this study exceeded catchment-scale estimates reported for other volcanic islands or global averages during the early weathering phase, but were much lower in the intermediate and late phases. Nevertheless, total C drawdown was dominated by soil organic C sequestration (70–90 % share) rather than inorganic, weathering-induced CO2 consumption during early pedogenesis (≤4.3 ka), and the relative importance switched in the intermediate and late phases (90–95 % share of weathering-induced C drawdown at ≥166 ka). Dust deposition derived from a nearby ocean sediment core was <20 % of total basalt mass loss at the young and intermediate-aged sites, but reached 40–60 % at the older sites (>800 ka). Our results suggest that (1) young volcanic surfaces are very efficient (inorganic and organic) C sinks, (2) the development of thick soil covers at advanced pedogenic stages effectively shields the underlying rocks and decelerates weathering, and (3) dust inputs become an increasingly important biogeochemical factor in such highly weathered environments.

3D Bioprinting and Microfluidic-Based Devices for Cancer Detection and Drug Treatment: Focus on Prostate Cancer.

The burden of increasing cancer incidence among the population, and, in particular, of prostate cancer in men living in highly developed countries, brings with it, on one hand, the need for new devices that allow a faster and earlier diagnosis, ideally in a non-invasive way and with low consumption of expensive reagents, and on the other the need for the assessment of new in vitro models that allow a more reliable assessment of cancer features, including its microenvironment and sensibility to different drugs. At the crossroads of these features, microfluidic devices are found. These, taking advantage of the chemical-physical properties of cells and human samples, have demonstrated great sensitivity and sensibility at an on-chip scale. Many fields of biomedical sciences have tried to exploit all their potentialities: from the detection of antigens in the early phases of the disease (when they are very low concentrated, but the treatment is more effective) to isolation and characterization of circulating tumor cells. However, the development of in vitro 3D models to better assess and comprehend the fundamental dynamics of tumor microenvironment and metastasis using 3D bioprinting techniques. The aim of the present review is to describe the potential of these two different cutting-edge technologies for the detection and treatment of prostate cancer, in the perspective of a possible future combination of them that allows scientists to fill the gaps present in the field to improve patient care and treatment.

Resting-state functional magnetic resonance imaging reveals functional connectivity alteration in the experimental autoimmune encephalomyelitis model of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune degenerative disease targeting white matter in the central nervous system. The most common animal model that mimics MS is experimental autoimmune encephalomyelitis (EAE) and it plays a crucial role in pharmacological research, from the identification of a therapeutic target to the in vivo validation of efficacy. Magnetic resonance imaging (MRI) is largely used to detect MS lesions, and resting-state functional MRI (rsfMRI) to investigate alterations in the brain functional connectivity (FC). MRI was mainly used in EAE studies to detect lesions in the spinal cord and brain. The current longitudinal MRI study aims to validate rsfMRI as a biomarker of the disease progression in the myelin oligodendrocyte glycoprotein 35-55 induced EAE animal model of MS. MR images were acquired 14, 25, and 50 days postimmunization. Seed-based analysis was used to investigate the whole-brain FC with some predefined areas, such as the thalamic regions, cerebellum, motor and somatosensory cortex. When compared with the control group, the EAE group exhibited a slightly altered FC and a decreasing trend in the total number of activated voxels along the disease progression. The most interesting result regards the whole-brain FC with the cerebellum. A hyperconnectivity behavior was found at an early phase and a significant reduced connectivity at a late phase. Moreover, we found a negative correlation between the total number of activated voxels during the late phase and the cumulative disease index. The results obtained provide a clinically relevant experimental platform that may be pivotal for the elucidation of the key mechanisms of accumulation of irreversible disability, as well as the development of innovative therapies for MS. Moreover, the negative correlation between the disease severity and the size of the activated area suggests a possible research pathway to follow for the resolution of the clinico-radiological paradox.

Social representations of teachers' dropout in the French context: An exploratory study

AbstractThis work aims to investigate the causes behind teachers leaving their profession in France, as well as the aspects that influence some teachers to stay in. The phenomenon of teacher dropout and abandonment is increasingly prevalent in OECD countries, particularly affecting new teachers. Taking a social psychological perspective, the research delves into the representational content of teachers' attitudes towards their profession. By distinguishing between teacher dropout and abandonment—the latter being considered an earlier phase, the results suggest that pupils play a central role in preventing teachers' dropout, along with the love and passion for teaching and the discipline they teach. Conversely, lack of consideration, inadequate resources, working conditions and classroom management challenges are identified as aspects contributing to increase teachers' dropout phenomenon. The findings provide an empirical basis for future studies and valuable insights for enhancing initial teacher training programmes. Understanding these phenomena through the lens of social representations provides valuable insights for developing supportive environments that foster teacher retention and well‐being and facilitate intervention and prevention strategies targeting key elements linked to teachers dropping out.

Tectono-Metamorphic Evolution of the Cretaceous Kluane Schist, Southwest Yukon

Abstract A wealth of information regarding the Mesozoic evolution of the Northern Canadian and Alaskan Cordillera is held within a series of variably metamorphosed and deformed rocks that formed in Jura-Cretaceous basins. Located at the interface between the pericratonic Intermontane and exotic Insular terranes, these basinal rocks are key to understanding the timing and tectonic style of Insular terrane accretion, a topic of longstanding debate. This study unravels the structural and metamorphic evolution of one of these basins, the Kluane Basin, within southwest Yukon Territory. The Kluane Schist is the primary assemblage of the Kluane Basin. It consists of metamorphosed and deformed low-Al pelites that were intruded by granodioritic plutons of the Paleocene Ruby Range batholith. Previous workers have suggested the variable metamorphic character of the Kluane Schist represents an extensive and static thermal aureole related to Ruby Range batholith emplacement. Our work, however, indicates that the Kluane Schist experienced Buchan-style metamorphism coeval with protracted deformation and can be divided into seven distinct petrologic zones, which, based on their unique combination of mineral assemblage and structure, are incompatible with static thermal metamorphism. Instead, we propose the Kluane Schist experienced two distinct metamorphic phases: (1) an early greenschist-facies phase that resulted in the development of a bedding-parallel chlorite-muscovite-titanite fabric, preserved by its lowest-grade units, and (2) a later amphibolite-facies phase that manifests as the progressive transposition of the earlier chlorite-muscovite-titanite fabric into a penetrative biotite-rich schistosity that transitions upgrade into a segregated gneissic fabric comprised of biotite-cordierite and plagioclase-quartz (± sillimanite-K-feldspar-melt). By integrating the results of detailed petrography and petrological modeling, we demonstrate that the second main metamorphic phase experienced by the Kluane Schist preserves a record of pressures and temperatures that align with other Buchan-style terranes worldwide. Our data defines a field gradient across the Kluane Schist ranging from 3.0–3.5 kbar at 375–400 °C to 4–4.5 kbar at 700–750 °C. This record of a coupled Buchan-style metamorphic-deformational evolution and tops-to-the SW non-coaxial shear structures is consistent with the override of the thermally mature Yukon-Tanana terrane as the principal driver of Kluane Schist metamorphism, with some limited heat likely contributed by the late-syn- to post-tectonic intrusion of the Ruby Range batholith.

Bridging comic art and research: lessons from an interdisciplinary collaboration project in a palliative care context

The Dutch graphic novel Naasten, about palliative family caregiving, is the product of an interdisciplinary collaboration between researchers and two comic artists. This paper aims to present lessons, reflections and...

Risk factors and a nomogram for predicting cognitive frailty in Chinese patients with lung cancer receiving drug therapy: A single-center cross-sectional study.

To identify independent factors of cognitive frailty (CF) and construct a nomogram to predict cognitive frailty risk in patients with lung cancer receiving drug therapy. In this cross-sectional study, patients with lung cancer undergoing drug therapy from October 2022 to July 2023 were enrolled. The data collected includes general demographic characteristics, clinical data characteristics and assessment of tools for cognitive frailty and other factors. Logistic regression was harnessed to determine the influencing factors, R software was used to establish a nomogram model to predict the risk of cognitive frailty. The enhanced bootstrap method was employed for internal verification of the model. The performance of the nomogram was evaluated by using calibration curves, the area under the receiver operating characteristic curve, and decision curve analysis. A total of 372 patients were recruited, with a cognitive frailty prevalence of 56.2%. Age, education background, diabetes mellitus, insomnia, sarcopenia, and nutrition status were identified as independent factors. Then, a nomogram model was constructed and patients were classified into high- and low-risk groups with a cutoff value of 0.552. The internal validation results revealed good concordance, calibration and discrimination. The decision curve analysis presented prominent clinical utility. The prevalence of cognitive frailty was higher in lung cancer patients receiving drug therapy. The nomogram could identify the risk of cognitive frailty intuitively and simply in patients with lung cancer, so as to provide references for early screening and intervention for cognitive frailty at the early phases of drug treatment.