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Abstract Music is a promising (adjunctive) treatment for both acute and chronic pain, reducing the need for pharmacological analgesics and their side effects. Yet, little is known about the effect of different types of music. Hence, we investigated the efficacy of five music genres (Urban, Electronic, Classical, Rock and Pop) on pain tolerance. In this parallel randomized experimental study, we conducted a cold pressor test in healthy volunteers (n = 548). The primary outcome was pain tolerance, measured in seconds. No objective (tolerance time) or subjective (pain intensity and unpleasantness) differences were found among the five genres. Multinomial logistic regression showed that overall genre preference positively influenced pain tolerance. In contrast, the music genres that participants thought would help for pain relief did not. Our study was the first to investigate pain tolerance at genre level and in the context of genre preference without self-selecting music. In conclusion, this study provides evidence that listening to a favored music genre has a significant positive influence on pain tolerance, irrespective of the kind of genre. Our results emphasize the importance of individual music (genre) preference when looking at the analgesic benefits of music. This should be considered when implementing music in the clinical setting.

Abstract The standard method for identifying active Brown Adipose Tissue (BAT) is [18F]-Fluorodeoxyglucose ([18F]-FDG) PET/CT imaging, which is costly and exposes patients to radiation, making it impractical for population studies. These issues can be addressed with computational methods that predict [18F]-FDG uptake by BAT from CT; earlier population studies pave the way for developing such methods by showing some correlation between the Hounsfield Unit (HU) of BAT in CT and the corresponding [18F]-FDG uptake in PET. In this study, we propose training convolutional neural networks (CNNs) to predict [18F]-FDG uptake by BAT from unenhanced CT scans in the restricted regions that are likely to contain BAT. Using the Attention U-Net architecture, we perform experiments on datasets from four different cohorts, the largest study to date. We segment BAT regions using predicted [18F]-FDG uptake values, achieving 23% to 40% better accuracy than conventional CT thresholding. Additionally, BAT volumes computed from the segmentations distinguish the subjects with and without active BAT with an AUC of 0.8, compared to 0.6 for CT thresholding. These findings suggest CNNs can facilitate large-scale imaging studies more efficiently and cost-effectively using only CT.

Global warming is amplified in the Arctic. However, numerical models struggle to represent key processes that determine Arctic weather and climate. To collect data that help to constrain the models, the HALO–(𝒜𝒞)3 aircraft campaign was conducted over the Norwegian and Greenland seas, the Fram Strait, and the central Arctic Ocean in March and April 2022. The campaign focused on one specific challenge posed by the models, namely the reasonable representation of transformations of air masses during their meridional transport into and out of the Arctic via northward moist- and warm-air intrusions (WAIs) and southward marine cold-air outbreaks (CAOs). Observations were made over areas of open ocean, the marginal sea ice zone, and the central Arctic sea ice. Two low-flying and one long-range, high-altitude research aircraft were flown in colocated formation whenever possible. To follow the air mass transformations, a quasi-Lagrangian flight strategy using trajectory calculations was realized, enabling us to sample the same moving-air parcels twice along their trajectories. Seven distinct WAI and 12 CAO cases were probed. From the quasi-Lagrangian measurements, we have quantified the diabatic heating/cooling and moistening/drying of the transported air masses. During CAOs, maximum values of 3 K h−1 warming and 0.3 g kg−1 h−1 moistening were obtained below 1 km altitude. From the observations of WAIs, diabatic cooling rates of up to 0.4 K h−1 and a moisture loss of up to 0.1 g kg−1 h−1 from the ground to about 5.5 km altitude were derived. Furthermore, the development of cloud macrophysical (cloud-top height and horizontal cloud cover) and microphysical (liquid water path, precipitation, and ice index) properties along the southward pathways of the air masses were documented during CAOs, and the moisture budget during a specific WAI event was estimated. In addition, we discuss the statistical frequency of occurrence of the different thermodynamic phases of Arctic low-level clouds, the interaction of Arctic cirrus clouds with sea ice and water vapor, and the characteristics of microphysical and chemical properties of Arctic aerosol particles. Finally, we provide a proof of concept to measure mesoscale divergence and subsidence in the Arctic using data from dropsondes released during the flights.

Designing exotic structures in low dimensions is key in today’s quest to tailor novel quantum states in materials with unique symmetries. Particularly intriguing materials in this regard are low dimensional aperiodic structures with non-conventional symmetries that are otherwise forbidden in translation symmetric crystals. In our work, we focus on the link between the structural and electronic properties of aperiodically ordered aromatic molecules on a quasicrystalline surface, which has largely been neglected so far. As an exemplary case, we investigate the self-assembly and the interfacial electronic properties of the nano-graphene-like molecule coronene on the bulk truncated icosahedral (i) Al–Pd–Mn quasicrystalline surface using multiple surface sensitive techniques. We find an aperiodically ordered coronene monolayer (ML) film on the i-Al–Pd–Mn surface that is characterized by the same local motifs of the P1 Penrose tiling model as the bare i-Al–Pd–Mn surface. The electronic valence band structure of the coronene/i-Al–Pd–Mn system is characterized by the pseudogap of thebare i-Al–Pd–Mn, which persists the adsorption of coronene confirming the quasiperiodic nature of the interface. In addition, we find a newly formed interface state of partial molecular character that suggests an at least partial chemical interaction between the molecule and the quasicrystalline surface. We propose that this partial chemical molecule–surface interaction is responsible for imprinting the quasicrystalline order of the surface onto the molecular film.

Abstract When different researchers study the same research question using the same dataset they may obtain different and potentially even conflicting results. This is because there is often substantial flexibility in researchers’ analytical choices, an issue also referred to as “researcher degrees of freedom”. Combined with selective reporting of the smallest p-value or largest effect, researcher degrees of freedom may lead to an increased rate of false positive and overoptimistic results. In this paper, we address this issue by formalizing the multiplicity of analysis strategies as a multiple testing problem. As the test statistics of different analysis strategies are usually highly dependent, a naive approach such as the Bonferroni correction is inappropriate because it leads to an unacceptable loss of power. Instead, we propose using the “minP” adjustment method, which takes potential test dependencies into account and approximates the underlying null distribution of the minimal p-value through a permutation-based procedure. This procedure is known to achieve more power than simpler approaches while ensuring a weak control of the family-wise error rate. We illustrate our approach for addressing researcher degrees of freedom by applying it to a study on the impact of perioperative $$paO_2$$ p a O 2 on post-operative complications after neurosurgery. A total of 48 analysis strategies are considered and adjusted using the minP procedure. This approach allows to selectively report the result of the analysis strategy yielding the most convincing evidence, while controlling the type 1 error—and thus the risk of publishing false positive results that may not be replicable.

How air masses transform during meridional transport into and out of the Arctic is not well represented by numerical models. The airborne field campaign HALO-(𝒜𝒞)3 applied the High Altitude and Long-range Research Aircraft (HALO) within the framework of the collaborative research project on Arctic amplification (𝒜𝒞)3 to address this question by providing a comprehensive observational basis. The campaign took place from 7 March to 12 April 2022 in the North Atlantic sector of the Arctic, a main gateway of atmospheric transport into and out of the Arctic. Here, we investigate to which degree the meteorological and sea ice conditions during the campaign align with the long-term climatology (1979–2022). For this purpose, we use the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis v5 (ERA5), satellite data, and measurements at Ny-Ålesund, including atmospheric soundings. The observations and reanalysis data revealed two distinct periods with different weather conditions during HALO-(𝒜𝒞)3: the campaign started with a warm period (11–20 March 2022) where strong southerly winds prevailed that caused poleward transport of warm and moist air masses, so-called moist and warm air intrusions (WAIs). Two WAI events were identified as atmospheric rivers (ARs), which are narrow bands of strong moisture transport. These warm and moist air masses caused the highest measured 2 m temperatures (5.5 °C) and daily precipitation rates (42 mm d−1) at Ny-Ålesund for March since the beginning of the record (1993). Over the sea ice northwest of Svalbard, ERA5 indicated record-breaking rainfall. After the passage of a strong cyclone on 21 March 2022, a cold period followed. Northerly winds advected cold air into the Fram Strait, causing marine cold air outbreaks (MCAOs) until the end of the campaign. This second phase included one of the longest MCAO events found in the ERA5 record (19 d). On average, the entire campaign period was warmer than the climatological mean due to the strong influence of the ARs. In the Fram Strait, the sea ice concentration was well within the climatological variability over the entire campaign duration. However, during the warm period, a large polynya opened northeast of Svalbard, untypical for this season. Compared to previous airborne field campaigns focusing on the evolution of (mixed-phase) clouds, a larger variety of MCAO conditions was observed during HALO-(𝒜𝒞)3. In summary, air mass transport into and out of the Arctic was more pronounced than usual, providing exciting prospects for studying air mass transformation using HALO-(𝒜𝒞)3.

Abstract The prognostic value of radiomic quantitative features measured on pre-treatment 18F-FDG PET/CT was investigated in patients with follicular lymphoma (FL). We conducted a retrospective study of 126 FL patients (grade 1-3a) diagnosed between 2006 and 2020. A dozen of PET/CT-derived features were extracted via a software (Oncometer3D) from baseline 18F-FDG PET/CT images. The receiver operating characteristic (ROC) curve, Kaplan–Meier method and Cox analysis were used to assess the prognostic factors for progression of disease within 24 months (POD24) and progression-free survival at 24 months. Four different clusters were identified among the twelve PET parameters analyzed: activity, tumor burden, fragmentation-massiveness and dispersion. On ROC analyses, TMTV, the total metabolic tumor volume, had the highest AUC (0.734) followed by medPCD, the median distance between the centroid of the tumors and their periphery (AUC: 0.733). Patients with high TMTV (HR = 4.341; p

An accurate representation of the annual evolution of surface albedo of the Arctic Ocean, especially during the melting period, is crucial to obtain reliable climate model predictions in the Arctic. Therefore, the output of the surface albedo scheme of a coupled regional climate model (HIRHAM–NAOSIM) was evaluated against airborne and ground-based measurements. The observations were conducted during five aircraft campaigns in the European Arctic at different times of the year between 2017 and 2022; one of them was part of the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in 2020. We applied two approaches for the evaluation: (a) relying on measured input parameters of surface type fraction and surface skin temperature (offline) and (b) using HIRHAM–NAOSIM simulations independently of observational data (online). From the offline method we found a seasonally dependent bias between measured and modeled surface albedo. In spring, the cloud effect on surface broadband albedo was overestimated by the surface albedo parametrization (mean albedo bias of 0.06), while the surface albedo scheme for cloudless cases reproduced the measured surface albedo distributions for all seasons. The online evaluation revealed an overestimation of the modeled surface albedo resulting from an overestimation of the modeled cloud cover. Furthermore, it was shown that the surface type parametrization contributes significantly to the bias in albedo, especially in summer (after the drainage of melt ponds) and autumn (onset of refreezing). The lack of an adequate model representation of the surface scattering layer, which usually forms on bare ice in summer, contributed to the underestimation of surface albedo during that period. The difference between modeled and measured net irradiances for selected flights during the five airborne campaigns was derived to estimate the impact of the model bias for the solar radiative energy budget at the surface. We revealed a negative bias between modeled and measured net irradiances (median: −6.4 W m−2) for optically thin clouds, while the median value of only 0.1 W m−2 was determined for optically thicker clouds.

Esta conversación entre Howard Becker y Alain Pessin, publicada originalmente en 2006, es un texto ampliamente citado en la sociología de las artes ya que en él Howard Becker disecciona el pensamiento de Pierre Bourdieu, en concreto su concepto de "campo", y lo contrapone con su concepto de "mundos del arte". Ambas conceptualizaciones han sido clave en el desarrollo de la sociología del arte, y se han utilizado como sinónimos, o al menos como conceptos complementarios. Pero, como pone de manifiesto la entrevista, el punto de partida, las preguntas que se hacen y la forma de entender los trabajos artísticos difiere de forma profunda en ambos planteamientos.

Abstract Within carnivore guilds, dominant competitors (e.g., lions, Panthera leo) are limited primarily by the density of prey, while subordinate competitors (e.g., African wild dogs, Lycaon pictus) have been limited by the density of dominant competitors. Historically, the fitness and population density of subordinate competitors have not been tightly linked to prey density. However, populations of large herbivores have declined substantially across sub‐Saharan Africa due to human impacts, and where prey depletion is severe, fitness costs for competitive subordinates may begin to outweigh the benefits of competitive release. Using long‐term intensive monitoring of African wild dogs in Zambia's Luangwa Valley Ecosystem (LVE), we tested the effects of prey depletion on survival and reproduction. We hypothesized that African wild dog fitness would be lower in prey‐depleted areas, despite lower lion densities. Our study area included four contiguous regions that varied in protection level, prey density, and lion density. We fit Bayesian Cormack–Jolly–Seber and closed‐capture models to estimate effects on survival and population density, and generalized linear models to estimate effects on reproductive success. We found that the LVE is a stronghold for African wild dogs, with an estimated median density of 4.0 individuals/100 km2. Despite this high density, survival and reproduction differed among regions, and both components of fitness were substantially reduced in the region with the lowest prey density. Anthropogenic prey depletion is becoming an important limiting factor for African wild dogs. If prey depletion (or any other form of habitat degradation) becomes severe enough that its fitness costs outweigh the benefits of competitive release, such changes can fundamentally alter the balance between limiting factors for competitively subordinate species.

Background: Integrating music into pain treatment demonstrates significant benefits, effectively reducing subjective pain levels and perioperative opioid requirements. Currently, the relationship between the impact of specific types of music and listeners’ socio-cultural background is still unclear. This is especially relevant given that sociological research indicates that these factors can have a notable influence on music preference and perception. Current evidence suggests that individuals who choose their own music may experience greater benefits. However, additional research is needed to comprehensively grasp whether the effect of (preferred) music on pain endurance remains consistent across different socio-cultural backgrounds. Methods: In this study, a collaborative effort between medical and sociological researchers aims to investigate music-induced analgesia differentiated by socio-cultural background in healthy volunteers. Participants (n = 84) will listen to self-, and researcher-chosen music and a podcast as a control condition in a cross-over study design. The primary outcome of this study is pain endurance measured by electric stimuli of increasing intensity. Detailed sociological validated questionnaires will be utilized. Considering the notable influence of educational level on music taste formation found in previous research and its crucial role as a source of socio-cultural differentiation, participants will be stratified based on their level of education. Discussion: This experimental study represents one of the first efforts to gain a socio-culturally differentiated understanding of the therapeutic potential of music. Consequently, this could pave the way to purposefully and inclusively implement personalized music in healthcare settings.

Abstract Lyme borreliosis (LB) is the most common vector‐borne disease in the Northern Hemisphere caused by spirochetes belonging to the Borrelia burgdorferi sensu lato (Bbsl) complex. Borrelia spirochetes circulate in obligatory transmission cycles between tick vectors and different vertebrate hosts. To successfully complete this complex transmission cycle, Bbsl encodes for an arsenal of proteins including the PFam54 protein family with known, or proposed, influences to reservoir host and/or vector adaptation. Even so, only fragmentary information is available regarding the naturally occurring level of variation in the PFam54 gene array especially in relation to Eurasian‐distributed species. Utilizing whole genome data from isolates (n = 141) originated from three major LB‐causing Borrelia species across Eurasia (B. afzelii, B. bavariensis, and B. garinii), we aimed to characterize the diversity of the PFam54 gene array in these isolates to facilitate understanding the evolution of PFam54 paralogs on an intra‐ and interspecies level. We found an extraordinarily high level of variation in the PFam54 gene array with 39 PFam54 paralogs belonging to 23 orthologous groups including five novel paralogs. Even so, the gene array appears to have remained fairly stable over the evolutionary history of the studied Borrelia species. Interestingly, genes outside Clade IV, which contains genes encoding for proteins associated with Borrelia pathogenesis, more frequently displayed signatures of diversifying selection between clades that differ in hypothesized vector or host species. This could suggest that non‐Clade IV paralogs play a more important role in host and/or vector adaptation than previously expected, which would require future lab‐based studies to validate.

Conventional building inspection, which requires in-person visits by a qualified inspector, can be costly, time-consuming, and even pose health and safety risks. The travel restrictions of the global Covid-19 pandemic further highlighted the need for remote inspection methods. Using reality capture techniques to create a digital 3D representation of the site offers promise for remote inspection of building work. This paper aims to assess different reality capture methods and their visualizations for remote inspection of building work through a case study conducted in Melbourne, Australia. The reality capture methods included terrestrial and mobile laser scanning, RGB-D imaging, and aerial photogrammetry using a UAV. Professional building inspectors participated in the evaluation process by conducting remote inspection based on the captured data and comparing it to the on-site experience. The assessment involved different visualizations of the data, including 3D panoramas, point clouds, and triangulated surface meshes. The results indicate that image visualisation and the ability to make measurement on images are desirable by professional inspectors. These findings support the adoption of reality capture techniques for remote inspection of building work, which can enhance the safety and efficiency of the process.

INTRODUCTION: A randomized controlled trial was designed to test the impact of involving husbands in antenatal health education on women's maternal health knowledge. METHODS: Total 442 women receiving antenatal services at a hospital in Kathmandu, Nepal were randomized into three groups: women who attended education sessions with their husbands, women who attended education sessions alone, and women who attended no education sessions (controls). At baseline and after delivery, women's maternal health knowledge and change in knowledge levels were compared between the groups. RESULTS: Compared to control group women, women educated with husbands increased their knowledge scores by an average of 0.61 points (95% CI=0.32-0.89, P

Purpose. To compare efficacy of balloon kyphoplasty in restoring vertebral height and correcting kyphosis in patients having vertebra plana with or without osteonecrosis. Methods. 12 women and 3 men (mean age, 76 years), who had a complete vertebra plana with or without osteonecrosis (n=8 vs n=7), underwent balloon kyphoplasty. No external manoeuvres were performed before or during balloon kyphoplasty, except for positioning the patients in a prone posture on the operating table. The anterior, middle, and posterior vertebral height and the kyphotic angle were measured pre- and post-operatively with a digital imaging system. The vertebral height was measured as a percentage of the adjacent normal vertebral height. Results. Respectively in vertebra plana patients with or without osteonecrosis, the mean corrections of (1) kyphosis were 10° and 4° (p=0.099), (2) anterior vertebral height were 33% and 5% (p

We report a case of cement leakage into the posterior spinal canal due to inadvertent pedicle perforation during balloon kyphoplasty. The leakage was corrected immediately without any sequelae. Features seen on radiography and the minimally invasive procedure used for removal are described. The postoperative radiographs of 100 consecutive patients treated with balloon kyphoplasty were subsequently reviewed. Only one patient had a similar leakage but had no neurological complications.

IntroductionWe conducted mental model interviews in Aotearoa NZ to understand perspectives of uncertainty associated with natural hazards science. Such science contains many layers of interacting uncertainties, and varied understandings about what these are and where they come from creates communication challenges, impacting the trust in, and use of, science. To improve effective communication, it is thus crucial to understand the many diverse perspectives of scientific uncertainty.MethodsParticipants included hazard scientists (n = 11, e.g., geophysical, social, and other sciences), professionals with some scientific training (n = 10, e.g., planners, policy analysts, emergency managers), and lay public participants with no advanced training in science (n = 10, e.g., journalism, history, administration, art, or other domains). We present a comparative analysis of the mental model maps produced by participants, considering individuals’ levels of training and expertise in, and experience of, science.ResultsA qualitative comparison identified increasing map organization with science literacy, suggesting greater science training in, experience with, or expertise in, science results in a more organized and structured mental model of uncertainty. There were also language differences, with lay public participants focused more on perceptions of control and safety, while scientists focused on formal models of risk and likelihood.DiscussionThese findings are presented to enhance hazard, risk, and science communication. It is important to also identify ways to understand the tacit knowledge individuals already hold which may influence their interpretation of a message. The interview methodology we present here could also be adapted to understand different perspectives in participatory and co-development research.

How can emergency management teams communicate to potentially impacted communities what a major event causing infrastructure outages might mean for them, and what they can do to prepare? In this paper we describe the process of creating a webtool for end users to visualise infrastructure outages that the Wellington region of New Zealand would face following a rupture of the Wellington fault. This webtool creates insight for three key groups: critical infrastructure owners, communities, and the emergency management sector itself. Critical infrastructure entities can use the tool to understand where they might consider infrastructure upgrades to mitigate gaps of delivery following a fault rupture, and to consider their emergency response plans for delivery in an emergency (leading to their consideration of ‘planning emergency levels of service’). Communities can use the tool to understand what infrastructure outages will mean at the household level in an emergency, including the considerable distances that some community members will have to walk to access services such as food and water and prepare for prolonged outages. Finally, with a greater knowledge of the gaps in delivery and of those community members that might need assistance with food and water collection, the emergency management sector can be better prepared. The methodology for creating the webtool is described, along with the insights that the completed webtool provides for emergency planning.

Background and objectivePost-stroke delirium (PSD) is a common complication in acute stroke patients, and guidelines recommend routine screening and various preventive and treatment measures. However, there is a substantial lack of standardized approaches in diagnostic and therapeutic management of PSD. Here, we aimed to develop a new pragmatic and easily assessable screening tool to predict PSD based on early parameters, which are already integral to acute stroke diagnostics.MethodsWe enrolled acute stroke patients admitted to our stroke unit or intensive care unit and developed the scoring system using retrospective single-center patient data. The Confusion Assessment Method for the Intensive Care Unit was used for prospective score validation. Logistic regression models were employed to analyze the association of early clinical and paraclinical parameters with PSD development.ResultsN = 525 patients (median age: 76 years; 45.7% female) were enrolled, with 29.7% developing PSD during hospitalization. The resulting score comprises 6 items, including medical history, clinical examination findings, and non-contrast computed tomography results at admission. Scores range from −15 to +15 points, with higher values indicating a higher likelihood of PSD, ranging from 4% to 79%. The accuracy was 0.85, and the area under the curve was 0.89.ConclusionThe new RAPID (Risk Assessment and PredIction of Delirium in acute stroke patients)-score shows high accuracy in predicting PSD among acute stroke patients and offers precise odds of PSD for each corresponding score value, utilizing routine early clinical and paraclinical parameters. It can identify high-risk populations for clinical study interventions and may be suitable to guide prophylactic PSD measures.

Background: Experimental coronary artery interventions are currently being performed on non-diseased blood vessels in healthy animals. To provide a more realistic pathoanatomical scenario for investigations on novel interventional and surgical therapies, we aimed to fabricate a stenotic lesion, mimicking the morphology and structure of a human atherosclerotic plaque. Methods: In an interdisciplinary setting, we engineered a casting mold to create an atherosclerotic plaque with the dimensions to fit in a porcine coronary artery. Oscillatory rheology experiments took place along with long-term stability tests assessed by microscopic examination and weight monitoring. For the implantability in future in vivo setups, we performed a cytotoxicity assessment, inserted the plaque in resected pig hearts, and performed diagnostic imaging to visualize the plaque in its final position. Results: The most promising composition consists of gelatin, cholesterol, phospholipids, hydroxyapatite, and fine-grained calcium carbonate. It can be inserted in the coronary artery of human-sized pig hearts, producing a local partial stenosis and interacting like the atherosclerotic plaque by stretching and shrinking with the vessel wall and surrounding tissue. Conclusion: This artificial atherosclerotic plaque model works as a simulating tool for future medical testing and could be crucial for further specified research on coronary artery disease and is going to help to provide information about the optimal interventional and surgical care of the disease.

Abstract: This open-label, phase 1 study evaluated the safety, pharmacokinetics, and maximum tolerated dose of AMG 232, an investigational oral, selective mouse double minute 2 homolog inhibitor in relapsed/refractory acute myeloid leukemia (AML). AMG 232 was administered orally once daily for 7 days every 2 weeks (7 on/off) at 60, 120, 240, 360, 480, or 960 mg as monotherapy (arm 1) or at 60 mg with trametinib 2 mg (arm 2). Dose-limiting toxicities (DLTs), adverse events (AEs), pharmacokinetics, clinical and pharmacodynamic response, and expression of p53 target genes were assessed. All 36 patients received AMG 232. No DLTs occurred in arm 1, and 360 mg was the highest test dose; dose escalation was halted due to gastrointestinal AEs at higher doses. One of ten patients in arm 2 had a DLT (grade 3 fatigue); 60 mg was the highest dose tested with trametinib. Common treatment-related AEs (any grade) included nausea (58%), diarrhea (56%), vomiting (33%), and decreased appetite (25%). AMG 232 exhibited linear pharmacokinetics unaffected by coadministration with trametinib. Serum macrophage inhibitor cytokine-1 and bone marrow expression of BAX, PUMA, P21, and MDM2 increased during treatment. Of 30 evaluable patients, 1 achieved complete remission, 4 had morphologic leukemia-free state, and 1 had partial remission. Four of 13 (31%) TP53-wild-type patients and 0 of 3 (0%) TP53-mutant patients were responders. AMG 232 was associated with gastrointestinal AEs at higher doses but had acceptable pharmacokinetics, on-target effects, and promising clinical activity warranting further investigation in patients with relapsed/refractory AML. This trial was registered at www.clinicaltrials.gov as #NCT02016729.

Few patients with cancer, including those with acute myeloid leukemia and high-grade myeloid neoplasms, participate in clinical trials. Broadening standard eligibility criteria may increase clinical trial participation. In this retrospective single-center analysis, we identified 442 consecutive newly diagnosed patients from 2014 to 2016. Patients were considered eligible if they had performance status 0-2, normal renal and hepatic function, no recent solid tumor, left ventricular ejection fraction (EF) ≥ 50%, and no history of congestive heart failure (CHF) or myocardial infarction (MI); ineligible patients failed to meet one or more of these criteria. We included 372 patients who received chemotherapy. Ineligible patients represented 40% of the population and had a 1-79-fold greater risk of death (95% CI 1.37, 2.33) than eligible patients. Very few patients had cardiac co-morbidities, including 2% with low EF, 4% with prior CHF, and 5% with prior MI. In multivariable analysis, ineligibility was associated with decreased survival [HR 1-44 (95% CI 1-07, 1-93)]. Allogeneic transplantation, performed in 150 patients (40%), was associated with improved survival [HR 0-66, 95% CI (0-48, 0-91)]. Therefore, standard eligibility characteristics identify a patient population with improved survival. Further treatment options are needed for patients considered ineligible for clinical trials.