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As the primary mechanism through which journalistic labour is organized within a newsroom, news beats are an important feature of journalistic research. However, within the extensive research that examines beat reporting and its specialties, there is little that examines how the media covers itself���or the media beat. This study explores the media beat in Australia, examining how media covered two major media change events: the loss of jobs at newspaper publisher Fairfax in 2012 and the potential closure of wire service Australian Associated Press (AAP) in 2020. In analysing reporting of change events in journalism through a framework of metajournalistic discourse, and through an analysis of 200 items, this study found that ���media beat��� journalists included more information about the adverse effects of job loss and disruption on news supply in 2020 than in 2012. Intermedia competition often shaped coverage, with journalists reporting change in rival media companies. Yet, how ���media beat��� reporters covered these changes varied in both years. The study also found that stakeholders from within and outside of media contribute to the development of change narratives in journalism by offering robust discussion of the implications of industry transformation for news quality and informed publics.

As automobiles have become an essential part to facilitate our daily life, Advanced Driver Assistance Systems (ADAS) have been gaining more and more interest in assisting drivers to enhance both safety and convenience. To respond timely in case of an emergency, ADAS needs to keep track of the driver’s health/consciousness, which is generally achieved by monitoring the driver’s vital signs including Respiration Rate (RR), Heart Rate (HR) and Heart Rate Variability (HRV). However, most of the state-of-art solutions need to assume that the human is stationary, which does not hold in practical driving scenarios. To tackle the problem, we propose a novel system, which can estimate driver’s RR, HR and Inter-Beat Intervals (IBI) in the presence of driver’s motion artifacts using commercial millimeter-wave (mmWave) radio. The system consists of two key components. First, to extract the reflection signals containing vital signals, the motion artifacts are first removed by a novel motion compensation module, followed by the periodicity check to identify the components with vital signals. Second, the respiration and heartbeat signals are reconstructed by jointly optimizing the decomposition of all the extracted compound vital signals over different range-azimuth bins. We evaluate the system performance in real driving environment and investigate the impact of different parameters including the device locations, pavement conditions and motion types. Experimental results show that the proposed system can achieve a median error of 0.16 Respiration Per Minute (RPM), 0.82 Beat Per Minute (BPM) and 46 ms for RR, HR and IBI estimations, corresponding to the relative accuracy of 99.17%, 98.94% and 94.11%, respectively.

BACKGROUND Obstructive sleep apnoea (OSA) episode related blood pressure (BP) surge may mediate the association of OSA with cardiovascular disease. However, BP is not measured during a clinical sleep study. METHOD We tested the feasibility of incorporating the Caretaker physiological monitor, which utilizes a novel continuous beat-to-beat (b-b) BP monitoring technology, into polysomnography (PSG) and aimed to characterize BP surges related to obstructive respiratory events. B-b BP was concurrently collected and merged with PSG data on a posthoc basis. We compared BP surge between mean respiratory (apnoea, hypopnea and desaturation-alone events) and nonrespiratory events (spontaneous or leg movement-related arousals). We examined the association of the degree of oxygen desaturation with BP surge in a given respiratory event combining all events. A total of 17 consecutive patients (12 men, mean 52 years old, nine diagnostic and eight split-night PSGs) undergoing clinically indicated PSG were included after excluding one patient with poor signal quality due to excessive movement. RESULTS Caretaker was well tolerated. Mean respiratory BP surge ranged from 5 to 19 mmHg [Median (IQR) = 13.9 (9.5--16.2)]. Mean BP surge between the respiratory and nonrespiratory events was similar [13.8 (4.5) vs. 14.9 (5.3) mmHg, P = 0.13]. Accounting for the count distribution of desaturation/BP surge data pair events, there was a linear correlation between the degree of oxygen desaturation and BP surge (R = 0.57, P

Background Pseudo-spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)-accelerated 4D flow MRI, it has not been validated in whole-heart applications. Hypothesis Pseudo-spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced. Study Type Prospective. Population Twelve healthy subjects and eight patients with valvular regurgitation. Field Strength/Sequence 3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady-state free precession sequences. Assessment Valvular blood flow was quantified using valve tracking. PROUD- and EPI-based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI-based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios. Statistical Tests We used repeated measures ANOVA, Bland-Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant. Results PROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve-averaged mean difference [limits of agreement width]: 3.2 +/- 0.8 [8.7 +/- 1.1] mL/beat for PROUD, 5.5 +/- 2.9 [13.7 +/- 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 +/- 1.2 [15.3 +/- 5.9] mL/beat for PROUD, 0.6 +/- 0.6 [19.3 +/- 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9. Conclusion PROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further. Level of Evidence 1 Technical Efficacy Stage 2

This study investigates the beat-to-beat relationships among Pulse Transit Times (PTTs) and Pulse Arrival Times (PATs) concomitantly measured from the heart to finger, ear and forehead vascular districts, and their correlations with continuous finger blood pressure. These aspects were explored in 22 young volunteers at rest and during cold pressure test (CPT, thermal stress), handgrip (HG, isometric exercise) and cyclo-ergometer pedalling (CYC, dynamic exercise). The starting point of the PTT measures was the opening of the aortic valve detected by the seismocardiogram. Results indicate that PTTs measured at the ear, forehead and finger districts are uncorrelated each other at rest, and during CPT and HG. The stressors produced district-dependent changes in the PTT variability. Only the dynamic exercise was able to induce significant changes with respect to rest in the PTTs mean values (-40%, -36% and -17%, respectively for PTTear, PTTfore, PTTfinger,), and synchronize their modulations. Similar trends were observed in the PATs. The isovolumic contraction time decreased during the stressors application with a minimum at CYC (-25%) reflecting an augmented heart contractility. The increase in blood pressure (BP) at CPT was greater than that at CYC (137 vs. 128 mmHg), but the correlations between beat-to-beat transit times and BP were maximal at CYC (PAT showed a higher correlation than PTT; correlations were greater for systolic than for diastolic BP). This suggests that pulse transit times do not always depend directly on the beat-to-beat BP values but, under specific conditions, on other factors and mechanisms that concomitantly also influence BP.

While the phenomenon of beat-deafness has been explored in clinical contexts, few studies have investigated how rhythmically challenged people experience the act of keeping time with music. Task-based semi-structured interviews were conducted with eight participants who self-identified as being unable to clap in time to a beat. Participants were asked to keep time with a gradated battery of musical stimuli using both claps and alternative gestures (e.g. head nodding, swaying) and to articulate their timekeeping experience and strategies. Analysis reveals three core themes: (a) an apparent disconnect between the act of identifying the beat and the physical act of clapping, (b) variation in strategies for keeping time depending on the type of musical example (i.e., whether the beat was explicitly played by a percussive instrument or not), and (c) variation in the ease of coordination and listening experience when a movement other than clapping was used to keep time. Despite being small in scale, this qualitative study sheds light on some of the underlying strategies and processes involved in beat abstraction and keeping time to music, informing options for the musical training of rhythmically challenged people.

An electrocardiogram (ECG) consists of complex segments, such as P-QRS-T waves. Manual ECG annotation is challenging and time-consuming, even for specialist physicians. The shortage of labelled ECG data is one of the essential factors that affect ECG intelligent analysis's long-term development. This study proposes an intelligent ECG-assisted annotation system, that not only supplements labelled data, but also significantly reduces the workload compared with manual annotation. Since beat annotation is the most basic and important part, a GAN-based generation model that can generate 14 types of simulation beats and a CNN-based beat pre-annotation model are proposed. The experimental results show that the simulation beat has high similarity to real beat and the accuracy of the pre-annotation model on the test set of 14 classes of beats is 99.28%. The proposed ECG intelligent annotation system's self-learning mechanism could improve pre-annotation performance and annotation efficiency by generating more labelled data. The proposed annotation system can also be extended to other data annotation applications.

Optical mapping is an imaging technique that is extensively used in cardiovascular research, wherein parameter-sensitive fluorescent indicators are used to study the electrophysiology and excitation-contraction coupling of cardiac tissues. Despite many benefits of optical mapping, eliminating motion artifacts within the optical signals is a major challenge, as myocardial contraction interferes with the faithful acquisition of action potentials and intracellular calcium transients. As such, excitation-contraction uncoupling agents are frequently used to reduce signal distortion by suppressing contraction. When compared with other uncoupling agents, blebbistatin is the most frequently used, as it offers increased potency with minimal direct effects on cardiac electrophysiology. Nevertheless, blebbistatin may exert secondary effects on electrical activity, metabolism, and coronary flow, and the incorrect administration of blebbistatin to cardiac tissue can prove detrimental, resulting in erroneous interpretation of optical mapping results. In this “Getting It Right” perspective, we briefly review the literature regarding the use of blebbistatin in cardiac optical mapping experiments, highlight potential secondary effects of blebbistatin on cardiac electrical activity and metabolic demand, and conclude with the consensus of the authors on best practices for effectively using blebbistatin in optical mapping studies of cardiac tissue.

This exploratory, qualitative study documents how journalists working for U.S. news organizations defined and refined the concept of a “gender beat” in the aftermath of the 2017 resurgence of the #...

Purpose: This study aimed to document the present status of medicinal plants used to boost the immunity to combat Coronavirus. Materials and Methods: For the assessment and use of herbs during the Covid 19 pandemic, surveys were conducted in different villages of Seraj block. The surveys were conducted during the spread of the pandemic from 2020 to 2021. Local people were interviewed and information on the utilization of local herbs during this pandemic was recorded. Information on parts used, the procedure of use, habit, habitat, etc. was also collected. Results: A total of 58 species of medicinal plants from 27 families and 42 genera were documented. Among them, the most dominant family was Rosaceae. Most of the plants such as Morchella sp, Naustratium officinale,Taraxacum officinale ,Urtica dioica ,Allium sp,Withania foraminifera, Curcuma longa, Cannabis, Mentha, Ocimum sanctum are rich in antioxidants and have a wide range of medicinal values used to treat cough, cold, fever, and bronchitis. All these plants were used traditionally to boost immunity. Due to the covid -19 pandemic, the utilization of these herbal plants has increased many folds in the area. These medicinal plants should be made available to scientists to design clinical trials. Integration of this concept would certainly develop drug therapy in the near future. Conclusion: The study found that the use of medicinal plants has increased during COVID-19 and most of the respondents recommended medicinal plants to prevent COVID-19 and to boost immunity. More studies should be conducted to develop certain formulations.

Auditory perception of time is superior to visual perception, both for simple intervals and beat-based musical rhythms. To what extent does this auditory advantage characterize perception of different hierarchical levels of musical meter, and how is it related to lifelong experience with music? We paired musical excerpts with auditory and visual metronomes that matched or mismatched the musical meter at the beat level (faster) and measure level (slower) and obtained fit ratings from adults and children (5-10 years). Adults exhibited an auditory advantage in this task for the beat level, but not for the measure level. Children also displayed an auditory advantage that increased with age for the beat level. In both modalities, their overall sensitivity to beat increased with age, but they were not sensitive to measure-level matching at any age. More musical training was related to enhanced sensitivity in both auditory and visual modalities for measure-level matching in adults and beat-level matching in children. These findings provide evidence for auditory superiority of beat perception across development, and they suggest that beat and meter perception develop quite gradually and rely on lifelong acquisition of musical knowledge. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

In medical practices, the detection of diseases highly depends on different medical tests. Electrocardiogram (ECG) technique is commonly used for heart disease diagnosis. Doctors can measure pulse and other heart boundaries with the aid of it. Fast and precise detection of forms of arrhythmia is critical while identifying heart disease. In this work, we proposed an intelligent ECG device (called iKardo) with the built-in automatic capability to classify into critical and non-critical data from an imbalanced ECG dataset for the smart IoT or Internet of Things based smart healthcare device. Particular emphasis is given to the reduction of data misclassification by converting imbalanced data into a balanced dataset using necessary techniques. This proposed iKardo helps in the accurate detection of critical ECG beats with an accuracy of 99.58% and result in a smart healthcare monitoring device that would make the disease detection fast and precise.

The Holter electrocardiogram from an asymptomatic man shows intermittent preexcitation. At the lowest rates all the QRS complexes display a WPW pattern. As the rate increases, preexcitation fails to occur and all the QRS complexes become persistently narrow. With a further increase in sinus rate the WPW occurs on alternate beats and this alternation is maintained for a while. A careful analysis of the accessory pathway conduction in relation to sinus-cycle length and morphology of the prior beat strongly supports the supernormal conduction through the Kent bundle associated with linking as the key mechanism underlying the preexcitation on alternate beats.

Online beat tracking (OBT) has always been a challenging task. Due to the inaccessibility of future data and the need to make inference in real-time. We propose Don’t Look back! (DLB), a novel approach optimized for efficiency when performing OBT. DLB feeds the activations of a unidirectional RNN into an enhanced Monte-Carlo localization model to infer beat positions. Most preexisting OBT methods either apply some offline approaches to a moving window containing past data to make predictions about future beat positions or must be primed with past data at startup to initialize. Meanwhile, our proposed method only uses activation of the current time frame to infer beat positions. As such, without waiting at the beginning to receive a chunk, it provides an immediate beat tracking response, which is critical for many OBT applications. DLB significantly improves beat tracking accuracy over state-of-the-art OBT methods, yielding a similar performance to offline methods.

Mass indoor gatherings were banned in early 2020 to prevent the spread of SARS-CoV-2. We aimed to assess, under controlled conditions, whether infection rates among attendees at a large, indoor gathering event would be similar to those in non-attendees, given implementation of a comprehensive prevention strategy including antigen-screening within 3 days, medical mask wearing, and optimised ventilation.The non-inferiority, prospective, open-label, randomised, controlled SPRING trial was done on attendees at a live indoor concert held in the Accor Arena on May 29, 2021 in Paris, France. Participants, aged 18-45 years, recruited via a dedicated website, had no comorbidities, COVID-19 symptoms, or recent case contact, and had had a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated in a 2:1 ratio to the experimental group (attendees) or to the control group (non-attendees). The allocation sequence was computer-generated by means of permuted blocks of sizes three, six, or nine, with no stratification. The primary outcome measure was the number of patients who were SARS-CoV-2-positive by RT-PCR test on self-collected saliva 7 days post-gathering in the per-protocol population (non-inferiority margin0·35%). This trial is registered with ClinicalTrials.gov, NCT04872075.Between May 11 and 25, 2021, 18 845 individuals registered on the dedicated website, and 10 953 were randomly selected for a pre-enrolment on-site visit. Among 6968 who kept the appointment and were screened, 6678 participants were randomly assigned (4451 were assigned to be attendees and 2227 to be non-attendees; median age 28 years; 59% women); 88% (3917) of attendees and 87% (1947) of non-attendees complied with follow-up requirements. The day 7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0·20%; 95% CI 0·09-0·40) and three of the 1947 non-attendees (0·15%; 0·03-0·45; absolute difference, 95% CI -0·26% to 0·28%), findings that met the non-inferiority criterion for the primary endpoint.Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2-transmission risk, provided a comprehensive preventive intervention was implemented.French Ministry of Health.For the French translation of the abstract see Supplementary Materials section.

We present a methodology that enables dance tempo estimation through the acquisition of 3D accelerometer signals using a single wearable inertial device positioned on the dancer’s leg. Our tempo estimation method is based on enhanced multiple resonators, implemented with comb feedback filters. To validate the methodology, we focus on the versatile solo jazz dance style. Including a variety of dance moves, with different leg activation patterns and rhythmical variations, solo jazz provides for a highly critical validation environment. We consider 15 different solo jazz dance moves, with different leg activation patterns, assembled in a sequence of 5 repetitions of each, giving 65 moves altogether. A professional and a recreational dancer performed this assembly in a controlled environment, following eight dancing tempos, dictated by a metronome, and ranging from 80 bpm to 220 bpm with 20 bpm increment steps. We show that with appropriate enhancements and using single leg signals, the comb filter bank provides for accurate dance tempo estimates for all moves and rhythmical variations considered. Dance tempo estimates for the overall assembles match strongly the dictated tempo—the difference being at most 1 bpm for all measurement instances is within the limits of the established beat onset stability of the used metronome. Results further show that this accuracy is achievable for shorter dancing excerpts, comprising four dance moves, corresponding to one music phrase, and as such enables real-time feedback. By providing for a dancer’s tempo quality and consistency assessment, the presented methodology has the potential of supporting the learning process, classifying individual level of experience, and assessing overall performance. It is extendable to other dance styles and sport motion in general where cyclical patterns occur.

The ECG signal processing methods are tested and evaluated based on many databases. The most ECG database used for many researchers is the MIT-BIH arrhythmia database. The QRS-detection algorithms are essential for ECG analyses to detect the beats for the ECG signal. There is no standard number of beats for this database that are used from numerous researches. Different beat numbers are calculated for the researchers depending on the difference in understanding the annotation file. In this paper, the beat numbers for existing methods are studied and compared to find the correct beat number that should be used. We propose a simple function to standardize the beats number for any ECG PhysioNet database to improve the waveform database toolbox (WFDB) for the MATLAB program. This function is based on the annotation's description from the databases and can be added to the Toolbox. The function is removed the non-beats annotation without any errors. The results show a high percentage of 71% from the reviewed methods used an incorrect number of beats for this database.

Neural activity in the auditory system synchronizes to sound rhythms, and brain-environment synchronization is thought to be fundamental to successful auditory perception. Sound rhythms are often operationalized in terms of the sound's amplitude envelope. We hypothesized that - especially for music - the envelope might not best capture the complex spectro-temporal fluctuations that give rise to beat perception and synchronized neural activity. This study investigated (1) neural synchronization to different musical features, (2) tempo-dependence of neural synchronization, and (3) dependence of synchronization on familiarity, enjoyment, and ease of beat perception. In this electroencephalography study, 37 human participants listened to tempo-modulated music (1-4 Hz). Independent of whether the analysis approach was based on temporal response functions (TRFs) or reliable components analysis (RCA), the spectral flux of music - as opposed to the amplitude envelope - evoked strongest neural synchronization. Moreover, music with slower beat rates, high familiarity, and easy-to-perceive beats elicited the strongest neural response. Our results demonstrate the importance of spectro-temporal fluctuations in music for driving neural synchronization, and highlight its sensitivity to musical tempo, familiarity, and beat salience.When we listen to a melody, the activity of our neurons synchronizes to the music: in fact, it is likely that the closer the match, the better we can perceive the piece. However, it remains unclear exactly which musical features our brain cells synchronize to. Previous studies, which have often used ‘simplified’ music, have highlighted that the amplitude envelope (how the intensity of the sounds changes over time) could be involved in this phenomenon, alongside factors such as musical training, attention, familiarity with the piece or even enjoyment. Whether differences in neural synchronization could explain why musical tastes vary between people is also still a matter of debate. In their study, Weineck et al. aim to better understand what drives neuronal synchronization to music. A technique known as electroencephalography was used to record brain activity in 37 volunteers listening to instrumental music whose tempo ranged from 60 to 240 beats per minute. The tunes varied across an array of features such as familiarity, enjoyment and how easy the beat was to perceive. Two different approaches were then used to calculate neural synchronization, which yielded converging results. The analyses revealed that three types of factors were associated with a strong neural synchronization. First, amongst the various cadences, a tempo of 60-120 beats per minute elicited the strongest match with neuronal activity. Interestingly, this beat is commonly found in Western pop music, is usually preferred by listeners, and often matches spontaneous body rhythms such as walking pace. Second, synchronization was linked to variations in pitch and sound quality (known as ‘spectral flux’) rather than in the amplitude envelope. And finally, familiarity and perceived beat saliency – but not enjoyment or musical expertise – were connected to stronger synchronization. These findings help to better understand how our brains allow us to perceive and connect with music. The work conducted by Weineck et al. should help other researchers to investigate this field; in particular, it shows how important it is to consider spectral flux rather than amplitude envelope in experiments that use actual music.

Timing is everything, but our understanding of the neural mechanisms of timing remains limited, particularly for timing of sequences. Temporal sequences can be represented relative to a recurrent beat (beat-based or relative timing), or as a series of absolute durations (non-beat-based or absolute timing). Neuroimaging work suggests involvement of the basal ganglia, supplementary motor area (SMA), the premotor cortices, and the cerebellum in both beat- and non-beat-based timing. Here we examined how beat-based timing and non-beat-based sequence timing were affected by modulating excitability of the supplementary motor area, the right cerebellum, and the bilateral dorsal premotor cortices, using transcranial direct current stimulation (tDCS). Participants were subjected to a sham stimulation session, followed an active stimulation session where anodal or cathodal 2mA tDCS was applied to the SMA, right premotor cortex, left premotor cortex, or the cerebellum. During both sessions, participants discriminated changes in rhythms which differentially engage beat-based or non-beat-based timing. Rhythm discrimination performance was improved by increasing SMA excitability, and impaired by decreasing SMA excitability. This polarity-dependent effect on rhythm discrimination was absent for cerebellar or premotor cortex stimulation, suggesting a crucial role of the SMA and/or its functionally connected networks in rhythmic timing mechanisms.

Motile cilia are hair-like cell extensions present in multiple organs of the body. How cilia coordinate their regular beat in multiciliated epithelia to move fluids remains insufficiently understood, particularly due to lack of rigorous quantification. We combine here experiments, novel analysis tools, and theory to address this knowledge gap. We investigate collective dynamics of cilia in the zebrafish nose, due to its conserved properties with other ciliated tissues and its superior accessibility for non-invasive imaging. We revealed that cilia are synchronized only locally and that the size of local synchronization domains increases with the viscosity of the surrounding medium. Despite the fact that synchronization is local only, we observed global patterns of traveling metachronal waves across the multiciliated epithelium. Intriguingly, these global wave direction patterns are conserved across individual fish, but different for left and right nose, unveiling a chiral asymmetry of metachronal coordination. To understand the implications of synchronization for fluid pumping, we used a computational model of a regular array of cilia. We found that local metachronal synchronization prevents steric collisions and improves fluid pumping in dense cilia carpets, but hardly affects the direction of fluid flow. In conclusion, we show that local synchronization together with tissue-scale cilia alignment are sufficient to generate metachronal wave patterns in multiciliated epithelia, which enhance their physiological function of fluid pumping.

Interlimb coordination is critical to the successful performance of simple activities in everyday life and it depends on precisely timed perception-action coupling. This is particularly true in music-making, where performers often use body-movements to keep the beat while playing more complex rhythmic patterns. In the current study, we used a musical rhythmic paradigm of simultaneous rhythm/beat performance to examine how interlimb coordination between voice, hands and feet is influenced by the inherent hierarchical relationship between rhythm and beat. Sixty right-handed participants—musicians, amateur-musicians and non-musicians—performed three short rhythmic patterns while keeping the underlying beat, using 12 different combinations of voice, hands and feet. Results revealed a bodily hierarchy with five levels 1) left foot, 2) right foot, 3) left hand, 4) right hand, 5) voice, implying a more precise task execution when the rhythm was performed with a limb occupying a higher level in the hierarchy than the limb keeping the beat. The notion of a bodily hierarchy implies that the role assigned to the different limbs is key to successful interlimb coordination: the performance level of a specific limb combination differs considerably, depending on which limb holds the supporting role of the beat and which limb holds the conducting role of the rhythm. Although performance generally increased with expertise, the evidence of the hierarchy was consistent in all three expertise groups. The effects of expertise further highlight how perception influences action: Embracing a predictive coding view, we discuss the possibility that musicians’ more robust metrical prediction models make it easier for musicians to attenuate prediction errors than non-musicians. Overall, the study suggests a comprehensive bodily hierarchy, showing how interlimb coordination is influenced by hierarchical principles in both perception and action.

This paper reports the performance study of classifying 12-lead ECG beat segments in the face of severe imbalance in the class sizes, which is typical of ECG data. The efficacy of data augmentation for class size balancing to improve the classification accuracy is well known. In the ECG domain, however, it has been overlooked or handled inadequately. We propose an amplitude-alteration approach to augment randomly selected ECG heartbeats separately as needed in individual ECG classes while not disrupting the timeline of the ECG signals. In addition, augmentations of training dataset and test dataset receive separate attentions, and four cases of data augmentation are considered depending on whether each dataset is augmented or not. The effects of the augmentation scheme was evaluated using ResNet, the deep learning technique reputed for its remarkable accuracy through unique skipping connections between layers; specifically, a time series version of ResNet was used. The results confirmed the key benefit of class-balancing the training dataset through the proposed data augmentation scheme and, additionally, showed some extra benefit of augmenting the test dataset through “test-time augmentation.” Further, we adopted the class activation map (CAM) to identify heat map signatures that would explain ECG beat classes. The results demonstrated that the CAM could be an effective visual aid to classifying ECG beats, especially with the proposed data augmentation scheme in place. In this paper the augmentation scheme, the associated experiments, and their results are discussed concretely.

In this work, we address the task of video background music generation. Some previous works achieve effective music generation but are unable to generate melodious music tailored to a particular video, and none of them considers the video-music rhythmic consistency. To generate the background music that matches the given video, we first establish the rhythmic relations between video and background music. In particular, we connect timing, motion speed, and motion saliency from video with beat, simu-note density, and simu-note strength from music, respectively. We then propose CMT, a Controllable Music Transformer that enables local control of the aforementioned rhythmic features and global control of the music genre and instruments. Objective and subjective evaluations show that the generated background music has achieved satisfactory compatibility with the input videos, and at the same time, impressive music quality. Code and models are available at https://github.com/wzk1015/video-bgm-generation., Accepted to ACM Multimedia 2021. Project website at https://wzk1015.github.io/cmt/

Background: In a case report of a progressive multiple sclerosis with cerebellar impairments, we reported that synchronisation of steps to beats was possible only at −12% of usual walking cadence during 1 minute of walking. Objectives and methods: Here, we investigate the effect of synchronisation using two different alignment approaches on the patient’s gait pattern over 2 minutes of walking, compared to walking in silence. Results and conclusion: This proof of concept showed that the adaptive approach was successful resulting in an improved gait pattern compared to the other conditions, providing preliminary evidence to support a full-scale intervention study.

Although hydrodynamic interactions and cooperative swimming of mammalian sperm are observed, the key factors that lead to attraction or repulsion in different confined geometries are not well understood. In this study, we simulate the 3-dimensional fluid-structure interaction of pairs of swimmers utilizing the Method of Regularized Stokeslets, accounting for a nearby wall via a regularized image system. To investigate emergent trajectories of swimmers, we look at different preferred beat forms, planar or quasi-planar (helical with unequal radii). We also explored different initializations of swimmers in either the same plane (co-planar) or with centerlines in parallel planes. In free space, swimmers with quasi-planar beat forms and those with planar beat forms that are co-planar exhibit stable attraction. The swimmers reach a maintained minimum distance apart that is smaller than their initial distance apart. In contrast, for swimmers initialized in parallel beat planes with a planar beat form, we observe alternating periods of attraction and repulsion. When the pairs of swimmers are perpendicular to a nearby wall, for all cases considered, they approach the wall and reach a constant distance between swimmers. Interestingly, we observe sperm rolling in the case of swimmers with preferred planar beat forms that are initialized in parallel beat planes and near a wall.

Edward Dorn is a Black Mountain poet closely aligned with the Beat Generation, and his comic-epic Gunslinger can be read as equally attuned to the humor and popular-culture allusions found in Beat writing as it is with Black Mountain poetics. The Gunslinger character in Dorn's poem is a simulacrum of Herbert Hoover’s rugged individualism—-an ideological simulacrum—-a simulation without any history to precede any notion of an authentic original conception, and this protagonist is paradoxically tied to his antagonist—-a simulacrum of ruthless capitalism, and another form of American rugged individualism, embodied in the poem by the character Howard Hughes. The Gunslinger is part of the American imagination's ability to conceive of a solitary figure of righteousness who will stand against unfavorable odds in the name of justice. Yet the source of this conception can also lead to the cutthroat entrepreneur. In Gunslinger, Dorn is trying to make his readers cognizant that the image of the Gunslinger as American rugged individualism is a simulacrum, that this image remains potent, and that this image is tied to the ruthlessness of capitalist society.

The open form poetics of the New American Poetry rejected traditional poetic and social forms in favor of spontaneity and improvisation. Through their use of the typewriter, Beat and Black Mountain writers practice an embodied poetics that recovers the experience of space-time from the time crisis of modernity, one example of the social conformity rejected by the avant garde. In Olson’s theory of Projective Verse, the typewriter produces a visual form on the page that is intended to be heard. This chapter argues that Beat-Black Mountain writers such as Jack Kerouac and Larry Eigner use the typewriter, in Olson’s “projective” or “percussive” sense, to produce irreducibly graphic texts that refuse the binary distinctions between writing and speaking, seeing and hearing, space and time.

The literary works of writers belonging to the Beat and Black Mountain circles reveal a specific approach to and interaction with the visual arts. Multi-authored and collaborative works were common in both groups, yet the activity of collaboration was practiced at different levels of regularity and proximity. While keeping in mind the interconnectedness of literary and artistic production of the time, this article focuses on the role played by the visual arts in shaping both Beat and Black Mountain’s poetics. It also analyses the role of each specific community in encouraging transdisciplinary exchanges and explores the particular involvement in collaborative projects of such authors as Jack Kerouac, Allen Ginsberg, William Burroughs, Robert Duncan, Charles Olson, Jonathan Williams, and Robert Creeley.

Background Evidence suggests that economic, social, and psychological circumstances brought about by the COVID-19 pandemic may have a serious impact on behavioral health. Men who have sex with men (MSM) are disproportionally impacted by HIV and stimulant use, the co-occurrence of which heightens HIV transmission risk and undermines nationwide treatment strategies as prevention efforts for ending the HIV epidemic. There is a paucity of information regarding the potential impact of the COVID-19 pandemic on the substance use and HIV medication adherence in this key vulnerable population—MSM who use stimulants and are living with HIV. Objective The aim of this qualitative study was to identify ways in which the COVID-19 pandemic has affected stimulant use and antiretroviral therapy (ART) adherence among a sample of MSM living with HIV. Methods Two focus groups were conducted in August 2020 via videoconferencing technology compliant with the Health Insurance Portability and Accountability Act. Potential participants from an established research participant registry at State University of New York Downstate Health Sciences University were invited and screened for study participation on the basis of inclusion criteria. A semistructured interview guide was followed. A general inductive approach was used to analyze the data. Findings in two general areas of interest, the impact of the COVID-19 pandemic on stimulant use and ART adherence, emerged directly from the raw data. Results A total of 12 ethnically diverse participants over the age of 25 years took part in the study. Results were heterogeneous in terms of the effects of the pandemic on both stimulant use and ART adherence among MSM living with HIV. Some men indicated increased or sustained stimulant use and ART adherence, and others reported decreased stimulant use and ART adherence. Reasons for these behavioral changes ranged from concerns about their own health and that of their loved ones to challenges brought about by the lack of daily structure during the lockdown phase of the pandemic and emotion regulation difficulties. Conclusions The COVID-19 pandemic has had a differential impact on stimulant use and ART medication adherence among MSM living with HIV. The reasons for behavioral change identified in this study may be salient intervention targets to support ART medication adherence and lower stimulant use among MSM in the aftermath of the of the COVID-19 pandemic, as well as beyond.

Cardiac arrhythmia refers to irregularities in heartbeats. Left undiagnosed arrhythmias can cause severe and potentially fatal complications. As a result, early finding of such abnormalities is critical. Electrocardiogram (ECG) is regularly used by medical professionals to diagnose and differentiate cardiac arrhythmias. As a result, there have been many deep learning methods over the years in an attempt to automate this process. But traditional deep learning methods require big training data which often clearly do not reflect the age, weight and gender spectrum of patients and are prone to misclassification when data from different demographics is shown. Hence, temporal features extracted from these datasets are demographically biased. Consequently, in this paper, we intend to introduce Optimum Recurrence Plot based Classifier (OptRPC); a dynamical systems-based method of classifying ECG beats by embedding them in higher dimensions and devising an optimized recurrence plot. A Convolutional Neural Network architecture is then used to classify these recurrence plots. The proposed scheme accomplished an overall accuracy of 98.67% and 98.48% on two benchmark databases and delivered better performance than the previous state-of-the-art methods.

Instructors often show rhythmic movements with speech in video lectures. However, the effects of these movements have not been tested in video lectures with an instructor and visual learning material. Results of Experiment 1 showed students in the beat gestures and head nods conditions showed significantly less attention to the visual learning material, more attention to the instructor, whereas in the beat gestures + head nods condition drew significantly more attention to both. In Experiment 2 we tested whether the complexity of the visual learning material moderated the effects of rhythmic movements on students’ learning. When the presentation was simple, students in the head nods + beat gestures condition showed more positive interaction, and significantly better recall and transfer. The results have implications for video designing: if an instructor and simple learning material are visible, she is encouraged to show beat gestures and head nods to mark important information.

In this paper, an alternative model of the systemic and pulmonary circulation systems using Windkessel-type elements to simulate structural heart defects is proposed. A lumped nonlinear model of ten states was obtained and was simulated using a fourth-order Runge-Kutta method. The model was first validated by comparing the normal dynamic behavior of the cardiovascular system which was parameterized with data corresponding to a healthy person. The ventricular volume, systemic and pulmonary blood flow, and blood pressure signals were obtained using the model to validate it. The presence of a Patent Ductus Arteriosus (PDA) congenital disease in patients with different degrees of severity was simulated to observe the consequent changes in hemodynamic variables. The stroke volume (SV) and cardiac output (CO) were calculated to quantify the impact of short-circuit heart defects. For a healthy person the SV was 58.6 ml/beat; there was an increase in the pulmonary CO of 63.26% for a short defect, and 86.31% for a larger defect. The model response was verified against the actual physiological effects for accuracy and the results can be useful in the design of diagnostic strategies for congenital heart diseases.

Auditory short-term memory is often conceived of as a unitary capacity, with memory for different auditory materials (such as syllables, pitches, rhythms) posited to rely on similar neural mechanisms. One spontaneous behavior observed in short-term memory studies is ‘chunking’. For example, individuals often recount digit sequences in groups, or chunks, of 3–4 digits, and chunking is associated with better performance. Chunking may also operate in musical rhythm, with beats acting as potential chunk boundaries for tones in rhythmic sequences. Similar to chunking, beat-based structure in rhythms also improves performance. Thus, it is possible that beat processing relies on the same mechanisms that underlie chunking of verbal material. The current fMRI study examined whether beat perception is indeed a type of chunking, measuring brain responses to chunked and ‘unchunked’ letter sequences relative to beat-based and non-beat-based rhythmic sequences. Participants completed a sequence discrimination task, and comparisons between stimulus encoding, maintenance, and discrimination were made for both rhythmic and verbal sequences. Overall, rhythm and verbal short-term memory networks overlapped substantially. When contrasting rhythmic and verbal conditions, rhythms activated basal ganglia, supplementary motor area, and anterior insula more than letter strings did, during both encoding and discrimination. Verbal letter strings activated bilateral auditory cortex more than rhythms did during encoding, and parietal cortex, precuneus, and middle frontal gyri more than rhythms did during discrimination. Importantly, there was a significant interaction in the basal ganglia during encoding: activation for beat-based rhythms was greater than for non-beat-based rhythms, but verbal chunked and unchunked conditions did not differ. The interaction indicates that beat perception is not simply a case of chunking, suggesting a dissociation between beat processing and chunking-based grouping mechanisms.

Background: IVO is an oral potent inhibitor of mutated IDH1 (IDH1m) enzyme, recently approved for the treatment (Tx) of ND adult patients (pts) with IDH1m AML ≥75 years old or with comorbidities precluding use of intensive induction chemotherapy, and adult pts with relapsed or refractory AML. In this Phase 2 sub-study of the Beat AML Master Trial, we evaluated the efficacy of IVO + AZA combination Tx in ND pts aged ≥60 years with IDH1m AML (ClinicalTrials.gov: NCT03013998) Methods: This open-label multicenter (16 sites / 9 enrolling) combination Tx study enrolled ND pts with R132 mIDH1 AML, utilizing the modified minimax Simon's 2-stage Phase 2 design. Pts received IVO + AZA for 6 cycles in the absence of disease progression (PD), unacceptable toxicity or stem cell transplant. Pts who achieved complete remission (CR)/complete remission with hematologic improvement (CRh)/complete remission with incomplete hematologic recovery (CRi) continued IVO + AZA for a total of 12 cycles, then IVO monotherapy until PD. Pts without CR/CRh/CRi after 6 cycles continued IVO + AZA if they demonstrated Tx benefit, as defined in Figure 1. Key eligibility included ND IDH1 R132 mutated AML pts aged ≥60 years and ECOG performance status 0 - 2 (Karnofsky ≥60). All pts received IVO 500 mg/day orally in continuous 28-day cycles + AZA 75 mg/m2 IV or SC on days 1-7 every 28 days. The primary endpoint was CR+CRh+CRi rate after 6 cycles of Tx. Response was assessed using modified 2017 ELN AML criteria. The modified minimax Simon's 2-stage design required 40 pts and tested the null hypothesis that the CR/CRh/CRi rate equaled 25% vs the alternative of 50% (one-sided alpha = 0.025, power 90%). Stage 1 required >5/16 responses for continued enrollment. Even though these criteria were met, the sponsor decided to discontinue the trial on 12/12/2019. Here we report the final primary endpoint results. Data were frozen 02/03/2021. Results: Between 07/2018 and 11/2019, 19 patients were enrolled with IDH1m AML; 18 started IVO + AZA Tx and are included in the analyses. At data freeze, 5 pts had died and 7 pts still on Tx were offered standard of care IVO. Median age of the pts was 75 years, 50% were ≥75 years, 61% were female and 89% were White (Table 1). The most common reasons for Tx discontinuation were trial discontinued by sponsor (7 or 39%), stem cell transplant (4 or 22%), and PD (3 or 17%). A total of 13 pts achieved CR/CRh/CRi (72%) by up to 6 cycles of Tx (Table 2 & Figure 2). Over the entire study period, 14 pts achieved CR/CRh/CRi (78%) with 8 CR (44%), 3 CRh (17%) and 3 CRi (17%). No deaths occurred within the first 60 days of Tx. After a median follow up of 19.8 months (mos), Page 2 median response duration was not reached, with 12-mos disease-free survival rate of 69%; also, median OS was not reached, with 12- and 18-mos OS rates of 100% and 73%, respectively. The median (range) time on Tx was 12 mos ( Conclusions: In ND pts with IDH1m AML and ≥60 years of age, IVO + AZA Tx was associated with a high CR/CRh/CRi rate, no early deaths (60 days) and a 1-year OS of 100%. IVO + AZA was acceptably tolerated and no unexpected toxicities occurred. Most common unique toxicities of IVO observed during the study were differentiation syndrome and QTc prolongation; these led to Tx discontinuation in only 1 pt. CR/CRh/CRi rate obtained with IVO +AZA is higher than that previously reported in studies with the individual agents or intensive chemotherapy approaches, suggesting a synergistic effect. Our overall response rate is similar to that reported recently for IVO + AZA in older ND IDH1 mutant AML pts, despite not including pts with morphologic leukemia-free state and partial remission. Based on these results, a global Phase 3 evaluation of IVO or placebo plus AZA is ongoing (NCT03173248). Figure 1 Figure 1. Disclosures Patel: BMS-Celgene, Agios: Membership on an entity's Board of Directors or advisory committees; Aptevo Therapeutics: Research Funding; Peerview: Honoraria. Ruppert: Telios Pharma: Consultancy. Borate: Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharma: Research Funding; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rampal: Membership on an entity's Board of Directors or advisory committees; Galecto, Inc.: Consultancy; Promedior: Consultancy. Stein: Syros Pharmaceuticals, Inc.: Consultancy; Daiichi Sankyo: Consultancy; PinotBio: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Jazz Pharmaceuticals: Consultancy; Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Syndax Pharmaceuticals: Consultancy. Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. Kovacsovics: AbbVie: Research Funding; Janssen Pharmaceuticals: Research Funding; Amgen Inc.: Research Funding; Novartis: Research Funding; Stemline: Honoraria; Jazz Pharmaceutials: Honoraria. Blum: Leukemia and Lymphoma Society: Research Funding; Nkarta: Research Funding; Celyad Oncology: Research Funding; Syndax: Honoraria; Xencor: Research Funding; Abbvie: Honoraria; Forma Therapeutics: Research Funding; AmerisourceBergen: Honoraria. Arellano: KITE Pharma, Inc: Consultancy; Syndax Pharmaceuticals, Inc: Consultancy. Schiller: Sangamo: Research Funding; Takeda: Research Funding; Ono-UK: Consultancy, Research Funding; Gamida Cell Ltd.: Research Funding; Tolero: Research Funding; Samus: Research Funding; Karyopharm: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Bio: Research Funding; Mateon: Research Funding; Genentech-Roche: Research Funding; FujiFilm: Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Actinium Pharmaceuticals, Inc: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Arog: Research Funding; Delta-Fly: Research Funding; Celator: Research Funding; Forma: Research Funding; Astellas: Honoraria, Research Funding, Speakers Bureau; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Regimmune: Research Funding; PrECOG: Research Funding; Constellation Pharmaceuticals: Research Funding; Trovagene: Research Funding; Elevate: Research Funding; Deciphera: Research Funding; Actuate: Research Funding; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi-Sankyo: Research Funding; Onconova: Research Funding; Geron: Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Abbvie: Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Biomed Valley Discoveries: Research Funding; Eli Lilly: Research Funding; ASH foundation: Other: Chair-unpaid; Sellas: Research Funding; Ono: Consultancy; Incyte: Consultancy; Ariad: Research Funding; AstraZeneca: Consultancy; Kaiser Permanente: Consultancy; Cyclacel: Research Funding; MedImmune: Research Funding; Ambit: Research Funding; Leukemia & Lymphoma Society: Research Funding; Bluebird Bio: Research Funding; Boehringer-Ingleheim: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Olin: Actinium: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Cellectis: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; Daiichi Sankyo: Research Funding; Astellas: Honoraria, Research Funding. Foran: pfizer: Honoraria; gamida: Honoraria; servier: Honoraria; kura: Research Funding; abbvie: Research Funding; takeda: Research Funding; trillium: Research Funding; revolution medicine: Honoraria; novartis: Honoraria; certara: Honoraria; sanofi aventis: Honoraria; bms: Honoraria; syros: Honoraria; taiho: Honoraria; OncLive: Honoraria; actinium: Research Funding; aptose: Research Funding; boehringer ingelheim: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Litzow: Pluristem: Research Funding; Astellas: Research Funding; AbbVie: Research Funding; Jazz: Other: Advisory Board; Amgen: Research Funding; Actinium: Research Funding; Omeros: Other: Advisory Board; Biosight: Other: Data monitoring committee. Lin: AbbVie, Aptevo Therapeutics, Astellas Pharma, Bio-Path Holdings, Celgene, Celyad, Genentech-Roche, Gilead Sciences, Incyte, Jazz Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, Prescient Therapeutics, Seattle Genetics, Tolero, Trovagene: Research Funding. Foster: Agios: Consultancy; Daiichi Sankyo: Consultancy; Macrogenics: Consultancy; Rafael Pharmaceuticals: Research Funding; Macrogenics: Research Funding; Bellicum Pharmaceuticals: Research Funding. Cogle: Celgene: Membership on an entity's Board of Directors or advisory committees; Aptevo therapeutics: Research Funding. Vergilio: Roche: Current equity holder in publicly-traded company; Foundation Medicine: Current Employment. Gana: Bausch: Current holder of individual stocks in a privately-held company; The Leukemia & Lymphoma Society: Consultancy. Druker: The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; EnLiven: Consultancy, Research Funding; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; GRAIL: Current equity holder in publicly-traded company; Nemucore Medical Innovations, Inc.: Consultancy; Merck & Co: Patents & Royalties; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Bristol-Myers Squibb: Research Funding; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Iterion Therapeutics: Membership on an entity's Board of Directors or advisory committees; Recludix Pharma, Inc.: Consultancy; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; Aileron: Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Vincerx Pharma: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees. Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees. Levine: QIAGEN: Membership on an entity's Board of Directors or advisory committees; Imago: Membership on an entity's Board of Directors or advisory committees; Ajax: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees; Zentalis: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria; Celgene: Research Funding; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Research Funding; Incyte: Consultancy; Janssen: Consultancy; Astellas: Consultancy; Morphosys: Consultancy; Gilead: Honoraria; Amgen: Honoraria; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Prelude: Membership on an entity's Board of Directors or advisory committees; Auron: Membership on an entity's Board of Directors or advisory committees. Mims: Leukemia and Lymphoma Society: Consultancy; Kura Oncology: Consultancy; Genentech: Consultancy; Abbvie: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Aptevo: Research Funding; Xencor: Research Funding; Glycomemetics: Research Funding; Jazz Pharmaceuticals: Consultancy; Daiichi-Saynko: Consultancy. OffLabel Disclosure: IVO is an oral potent inhibitor of mutated IDH1 enzyme, recently approved for the treatment of ND adult patients with IDH1m AML âââ,¬Â°Ã,Â¥75 years old or with comorbidities precluding use of intensive induction chemotherapy, and adult pts with relapsed or refractory AML. The combination of AZA, a hypomethylating agent, and venetoclax, an oral BCL-2 inhibitor, is also FDA approved for newly diagnosed AML in adults 75 years or older, or who have comorbidities precluding intensive chemotherapy. This presentation will discuss the combination of IVO and AZA.

Background: GILT is an oral potent selective FLT3 kinase inhibitor approved for marketing for the treatment (Tx) of patients (pts) with relapsed/refractory FLT3 mutated (FLT3m) AML but efficacy in older ND FLT3m AML pts is unknown. Furthermore, FLT3m can be present as a dominant or subclone and impact of FLT3 inhibitor therapy in this setting is uncertain. Here we report the results of a Phase 2/1b sub-study of the Beat AML Master Trial to assess the efficacy of GILT monotherapy (GILTm) in ND FLT3m AML pts aged ≥60 years with high and low VAF and the subsequent response-driven addition of DEC Tx. (ClinicalTrials.gov NCT03013998) Methods: The study was an open-label multicenter (15 sites), 3-outcome, 2-stage Phase 2 design that assigned pts to either Dominant FLT3/Group 1 (GP1) or Non-Dominant FLT3/Group 2 (GP2) as shown in Figure 1. Key eligibility criteria included ND FLT3m AML pts with high and low VAF and/or ITD ratio, aged ≥60 years, and ECOG performance status 0-2. In the Phase 2 study, all pts received GILTm 120 mg/day on days 1 - 28. Pts without CR/CRi after cycle 2 were transferred to the Phase 1b study to receive GILT + DEC (Figure 1). Phase 1b study utilized a standard 3+3 design to evaluate the safety/tolerability of concurrent GILT + DEC. Pts received GILT (dose level 1 [DL1] = 80 mg/day or dose level 2 [DL2] = 120 mg/day on days 1-28) + DEC 20 mg/m 2 IV on days 1-10 or 1-5 every 28 days. Primary endpoint was CR+CRi rate (Phase 2). Response was assessed using modified 2017 ELN AML criteria. The non-dominant GP2 was stopped for futility, GP1 was stopped early to modify trial to include venetoclax. Results: Phase 2 - Between 9/10/2018 to 2/11/2020, 19 / 20 enrolled pts (GP1: n = 9; GP2: n = 10) received GILTm and were included in analyses. Baseline pt characteristics are shown in Table 1. Median (range) time on GILTm was 3 cycles (1 - 18) in GP1 and 1 cycle (1 - 9) in GP2. Most common reasons for discontinuing Tx were Tx failure (TF; 44%) and relapse (33%) in GP1 and TF (70%) and disease progression (PD; 20%) in GP2. Overall CR+CRi was achieved in 4 pts (44%) in GP1 and 1 pt (10%) in GP2. Response duration are shown in Table 2. After median follow-up of 14.3 months (mos) and 19 mos in GP1 and GP2, respectively, 1-year OS was 56% and 76%. Most common Grade ≥3 adverse events (AEs) were febrile neutropenia and colitis (each 25%) in GP1; anemia and low platelet count in GP2 (each 30%). Overall, 7 pts had 15 serious AEs (SAEs) and all SAEs occurred in GP1 pts; most common SAE was colitis (25%) and 1 pt (13%) had a Tx-related Grade 3 SAE of tumor lysis syndrome. In GP2, 1 pt (10%) had Tx-related Grade 2 AE of differentiation syndrome. In GP1, 2 pts died within 60 days of Tx and none in GP2. Phase1b - After up to 2 cycles of GILTm, 12 pts with no CR/CRi (GP1: n = 4; GP2: n = 8) were transferred to receive GILT + DEC (Figure 1). At the time of this report, 1 pt with CRh remained on Tx. Median total time on Tx (including GILTm) was 4 cycles and median time on GILT + DEC Tx was 3 cycles (Table 2). Most common reasons for discontinuing Tx were PD (33%) and TF (25%); and 2 pts (17%) stopped Tx due to an AE. Pts were treated with DL1 GILT + DEC (n = 3), then DL2 GILT + DEC (n = 9); only 1 pt had dose-limiting toxicity (DLT) at DL2 (Grade 3 hyperbilirubinemia and pneumonitis requiring steroid therapy), hence, DL2 GILT + DEC was considered the MTD. CR+CRi rate was 25% in 3 pts, all at DL2 (Table 2). After a median follow-up of 17.8 mos, the 1-year OS from start of GILT + DEC Tx was 57%. Most common Grade ≥3 Tx-related AEs were anemia, febrile neutropenia and low WBC count (each 22%). Overall, 6 pts had 12 SAEs; 1 pt with SAE of Grade 4 sepsis died. Three GILT-related SAEs occurred in 1 pt - Grade 3 hyperbilirubinemia, and pneumonitis and Grade 1 transaminases increased. One pt died within 30 days and a second within 60 days of Tx. No difference was observed in GILT pharmacokinetics (PK) with or without DEC, however steady state Ctrough values were 1.4 to 2.3-fold greater than in relapsed/refractory AML pts (Admiral trial). Conclusions: In ND pts ≥60 years old with dominant FLT3 AML, GILTm induced a high 44% CR+CRi rate and long median OS (21.7 mos). Pts with non-dominant FLT3 had low 10% CR+CRi rate. GILTm was generally safe and was associated with differentiation syndrome in 1 pt. Concurrent GILT + DEC was acceptably tolerated, only 1 pt had a DLT, and the MTD was 120 mg/day GILT + DEC. A subset of pts with no CR/CRi during GILTm achieved remission with addition of DEC. Based on these results, a triple combination Tx study with venetoclax is currently enrolling. Figure 1 Figure 1. Disclosures Traer: Genentech: Membership on an entity's Board of Directors or advisory committees; Schrodinger: Research Funding; Incyte: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier/Agios: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; ImmunoGen: Membership on an entity's Board of Directors or advisory committees. Mims: Glycomemetics: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Aptevo: Research Funding; Leukemia and Lymphoma Society's Beat AML clinical study: Consultancy, Research Funding; Genentech: Consultancy; Xencor: Research Funding; Kartos Pharmaceuticals: Research Funding; Abbvie: Consultancy; BMS: Consultancy; Kura Oncology: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding. Stein: Agios Pharmaceuticals, Inc: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Syndax Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Syros Pharmaceuticals, Inc.: Consultancy; PinotBio: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Jazz Pharmaceuticals: Consultancy; Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy. Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. Kovacsovics: AbbVie: Research Funding; Jazz Pharmaceutials: Honoraria; Janssen Pharmaceuticals: Research Funding; Amgen Inc.: Research Funding; Stemline: Honoraria; Novartis: Research Funding. Blum: Xencor: Research Funding; Abbvie: Honoraria; Nkarta: Research Funding; Celyad Oncology: Research Funding; AmerisourceBergen: Honoraria; Forma Therapeutics: Research Funding; Leukemia and Lymphoma Society: Research Funding; Syndax: Honoraria. Arellano: Syndax Pharmaceuticals, Inc: Consultancy; KITE Pharma, Inc: Consultancy. Schiller: Actinium Pharmaceuticals, Inc: Research Funding; Mateon: Research Funding; Tolero: Research Funding; Geron: Research Funding; Regimmune: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Celator: Research Funding; Sangamo: Research Funding; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Takeda: Research Funding; PrECOG: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Karyopharm: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell Ltd.: Research Funding; FujiFilm: Research Funding; Samus: Research Funding; Trovagene: Research Funding; Daiichi-Sankyo: Research Funding; Constellation Pharmaceuticals: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Abbvie: Research Funding; Actuate: Research Funding; Arog: Research Funding; Delta-Fly: Research Funding; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Agios: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Elevate: Research Funding; Ono-UK: Consultancy, Research Funding; Onconova: Research Funding; Deciphera: Research Funding; Astellas: Honoraria, Research Funding, Speakers Bureau; Forma: Research Funding; Genentech-Roche: Research Funding; Bio: Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Biomed Valley Discoveries: Research Funding; Eli Lilly: Research Funding; ASH foundation: Other: Chair-unpaid; Sellas: Research Funding; Ono: Consultancy; Incyte: Consultancy; Ariad: Research Funding; AstraZeneca: Consultancy; Kaiser Permanente: Consultancy; Cyclacel: Research Funding; MedImmune: Research Funding; Ambit: Research Funding; Leukemia & Lymphoma Society: Research Funding; Bluebird Bio: Research Funding; Boehringer-Ingleheim: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Olin: Astellas: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Genentech: Research Funding; Pfizer: Research Funding; Cellectis: Research Funding; Amgen: Honoraria; Abbvie: Honoraria; Actinium: Honoraria. Foran: taiho: Honoraria; syros: Honoraria; kura: Research Funding; boehringer ingelheim: Research Funding; sanofi aventis: Honoraria; trillium: Research Funding; aptose: Research Funding; abbvie: Research Funding; pfizer: Honoraria; gamida: Honoraria; actinium: Research Funding; takeda: Research Funding; certara: Honoraria; OncLive: Honoraria; bms: Honoraria; revolution medicine: Honoraria; servier: Honoraria; novartis: Honoraria; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Litzow: AbbVie: Research Funding; Jazz: Other: Advisory Board; Pluristem: Research Funding; Amgen: Research Funding; Omeros: Other: Advisory Board; Actinium: Research Funding; Astellas: Research Funding; Biosight: Other: Data monitoring committee. Lin: AbbVie, Aptevo Therapeutics, Astellas Pharma, Bio-Path Holdings, Celgene, Celyad, Genentech-Roche, Gilead Sciences, Incyte, Jazz Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, Prescient Therapeutics, Seattle Genetics, Tolero, Trovagene: Research Funding. Patel: BMS-Celgene, Agios: Membership on an entity's Board of Directors or advisory committees; Peerview: Honoraria; Aptevo Therapeutics: Research Funding. Foster: Bellicum Pharmaceuticals: Research Funding; Macrogenics: Research Funding; Rafael Pharmaceuticals: Research Funding; Macrogenics: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy. Cogle: Aptevo therapeutics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Vergilio: Foundation Medicine: Current Employment. Gana: The Leukemia & Lymphoma Society: Consultancy; Bausch: Current holder of individual stocks in a privately-held company. Druker: VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; GRAIL: Current equity holder in publicly-traded company; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; EnLiven: Consultancy, Research Funding; Iterion Therapeutics: Membership on an entity's Board of Directors or advisory committees; Recludix Pharma, Inc.: Consultancy; Pfizer: Research Funding; Merck & Co: Patents & Royalties; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Nemucore Medical Innovations, Inc.: Consultancy; Bristol-Myers Squibb: Research Funding; Blueprint Medicines: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Aileron: Membership on an entity's Board of Directors or advisory committees; Vincerx Pharma: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees. Byrd: Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Newave: Membership on an entity's Board of Directors or advisory committees. Levine: Auron: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Ajax: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Celgene: Research Funding; Roche: Honoraria, Research Funding; Zentalis: Membership on an entity's Board of Directors or advisory committees; Prelude: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Consultancy; Gilead: Honoraria; Morphosys: Consultancy; Imago: Membership on an entity's Board of Directors or advisory committees; QIAGEN: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria. Borate: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharma: Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rampal: Membership on an entity's Board of Directors or advisory committees; Galecto, Inc.: Consultancy; Promedior: Consultancy.

Background: In vitro studies and emerging clinical data suggest that inhibition of spleen tyrosine kinase may have an antileukemic effect in human AML. Pts with AML and TP53 mutations (TP53m) are commonly associated with older age (≥60 years) and complex karyotype (CK) and respond poorly to standard 7 + 3 induction (IND) chemotherapy with Methods: This multicenter (13 sites), open-label, Phase 2 combination Tx study utilized Simon's 2-stage Phase 2 design and enrolled AML pts with TP53m (identified molecularly) ± CK (Cohort A) or CK (≥3 metaphase abnormalities) without TP53m (Cohort B). Pts initially received 5 days of ENTO lead-in (which was later discontinued), followed by ENTO + DEC and those who achieved CR/CRh/CRi/MLFS with up to 3 cycles of IND proceeded to consolidation (CON) Tx for up to 11 cycles (Figure 1). Pts with CRi/MLFS after IND were allowed up to 6 cycles (IND + CON) to achieve CR/CRh or stayed on Tx if they got clinical benefit or went off Tx. CON was followed by maintenance (MTN) Tx for up to 2 years from start of study Tx. Pts were eligible if aged ≥60 years, ND, and had ECOG performance status 0 - 2. Pts received ENTO 400 mg orally twice daily for 5 days during ENTO lead-in, and then every 28 days during IND, CON, and MTN + DEC 20 mg/m 2 IV days 1-10 (IND) or days 1-5 (CON) every 28 days. Response was assessed using modified 2017 ELN AML criteria. The primary endpoint was composite complete remission (CCR) rate (CR + CRh) with up to 3 cycles of IND, and CRi/MLFS that achieved CR/CRh by up to 6 cycles (IND + CON). Beyond stage 1, pt accrual to Cohort A was allowed based on pts with CRi and to Cohort B was stopped early for futility. Results: Between Oct 2017 and Feb 2020, of the 63 pts enrolled (Cohort A = 48; Cohort B = 15), pts with confirmed eligibility who started study Tx were included in the analyses (Cohort A = 45; Cohort B = 13). During lead-in, 27 pts in Cohort A and 6 pts in Cohort B received ENTOm for 5 days. All pts received ENTO + DEC except 1 pt in Cohort A who withdrew consent (WOC). Median ages of the pts were 70 years (range 60 - 84) in Cohort A and 74 years (range 65 - 86) in Cohort B. Median time (range) on Tx was 2.2 mos and 4.8 mos in Cohort A and B, respectively. Most common reasons for Tx discontinuation were adverse event (AE; 27%), Tx failure (TF; 27%) and WOC (18%) in Cohort A; TF (31%), disease progression and relapse (each 15%) in Cohort B. In each cohort, 1 pt discontinued Tx due to death from leukemia and 1 pt in Cohort A in CRh due to development of an additional genetic abnormality. Four pts (9%) in Cohort A and 1 pt (8%) in Cohort B proceeded to transplant. The CCR (CR + CRh) rates with up to 6 cycles of Tx for Cohort A and B were 13.3% and 30.8%, respectively; overall CR + CRh rates were 17.8% and 38.5% (Table 1). In Cohort A, with a median follow-up of 11.5 months, 0% were 1-year disease-free and median OS (mOS) was 6.5 months. In Cohort B, with a median follow-up of 15.1 months, 25% were 1-year disease-free and mOS was 11.5 months. Deaths within 7-, 30-, and 60-days of Tx were 0, 3 and 11 in Cohort A and 0, 0 and 2 in Cohort B. Most common treatment-related Grade ≥3 AEs in Cohort A and B were febrile neutropenia (31% and 39%) and anemia (22% and 31%) (Table 2). Overall, 83 serious AEs (SAEs) were reported in 33 pts in Cohort A and 12 SAEs in 6 pts in Cohort B; most common SAEs in Cohort A were pneumonia (18%) and respiratory failure (11%), and in Cohort B sepsis, dehydration and acute kidney injury (each 15%). Most common treatment-related grade ≥3 laboratory abnormalities in Cohort A and B were neutrophils decreased (27% and 31%), WBC count decreased (20% and 23%), and lymphocyte count decreased (18% and 15%). Conclusions: ENTO + DEC demonstrated activity in ND AML pts aged ≥60 years with TP53m ± CK and CK without TP53 but induced low CR/CRh rates and short OS consistent with previously published poor CR rates and OS in these pts. Our results differ from the high remission rate and longer OS previously reported for DEC monotherapy in AML pts with TP53m. ENTO + DEC was safe and acceptably tolerated. Novel Tx strategies that can benefit AML pts with these most adverse risk factors are urgently needed. Figure 1 Figure 1. Disclosures Ruppert: Telios Pharma: Consultancy. Mims: Leukemia and Lymphoma Society's Beat AML clinical study: Consultancy, Research Funding; Aptevo: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Glycomemetics: Research Funding; Kartos Pharmaceuticals: Research Funding; Xencor: Research Funding; Genentech: Consultancy; Abbvie: Consultancy; BMS: Consultancy; Kura Oncology: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding. Borate: Jazz Pharma: Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rampal: Membership on an entity's Board of Directors or advisory committees; Galecto, Inc.: Consultancy; Promedior: Consultancy. Stein: Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Gilead Sciences, Inc.: Consultancy; Foghorn Therapeutics: Consultancy; Syros Pharmaceuticals, Inc.: Consultancy; Daiichi Sankyo: Consultancy; Blueprint Medicines: Consultancy; PinotBio: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Syndax Pharmaceuticals: Consultancy. Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria. Kovacsovics: AbbVie: Research Funding; Janssen Pharmaceuticals: Research Funding; Amgen Inc.: Research Funding; Novartis: Research Funding; Stemline: Honoraria; Jazz Pharmaceutials: Honoraria. Blum: Amerisource Bergen; Abbvie, Syndax: Honoraria; Forma Therapeutics, Xencor; Celyad: Research Funding. Arellano: KITE Pharma, Inc: Consultancy; Syndax Pharmaceuticals, Inc: Consultancy. Schiller: Actinium Pharmaceuticals, Inc: Research Funding; Gamida Cell Ltd.: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; Forma: Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; MedImmune: Research Funding; Ambit: Research Funding; Karyopharm: Research Funding; Daiichi-Sankyo: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kaiser Permanente: Consultancy; Abbvie: Research Funding; AstraZeneca: Consultancy; Genentech-Roche: Research Funding; Delta-Fly: Research Funding; Cyclacel: Research Funding; Mateon: Research Funding; Actuate: Research Funding; Onconova: Research Funding; Geron: Research Funding; Sangamo: Research Funding; Arog: Research Funding; Ariad: Research Funding; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Takeda: Research Funding; Trovagene: Research Funding; Ono-UK: Consultancy, Research Funding; Tolero: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Celator: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy; Novartis: Consultancy, Research Funding; Deciphera: Research Funding; FujiFilm: Research Funding; Samus: Research Funding; Regimmune: Research Funding; PrECOG: Research Funding; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Bio: Research Funding; Elevate: Research Funding; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Biomed Valley Discoveries: Research Funding; Ono: Consultancy; Eli Lilly: Research Funding; Sellas: Research Funding; ASH foundation: Other: Chair-unpaid; Leukemia & Lymphoma Society: Research Funding; Bluebird Bio: Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Boehringer-Ingleheim: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Olin: Astellas: Honoraria, Research Funding; Actinium: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Cellectis: Research Funding; Daiichi Sankyo: Research Funding; Genentech: Research Funding; Pfizer: Research Funding. Foran: certara: Honoraria; pfizer: Honoraria; syros: Honoraria; taiho: Honoraria; boehringer ingelheim: Research Funding; servier: Honoraria; revolution medicine: Honoraria; trillium: Research Funding; takeda: Research Funding; abbvie: Research Funding; novartis: Honoraria; bms: Honoraria; OncLive: Honoraria; gamida: Honoraria; sanofi aventis: Honoraria; aptose: Research Funding; actinium: Research Funding; kura: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Litzow: AbbVie: Research Funding; Omeros: Other: Advisory Board; Astellas: Research Funding; Pluristem: Research Funding; Jazz: Other: Advisory Board; Actinium: Research Funding; Amgen: Research Funding; Biosight: Other: Data monitoring committee. Lin: AbbVie, Aptevo Therapeutics, Astellas Pharma, Bio-Path Holdings, Celgene, Celyad, Genentech-Roche, Gilead Sciences, Incyte, Jazz Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, Prescient Therapeutics, Seattle Genetics, Tolero, Trovagene: Research Funding. Cogle: Aptevo therapeutics: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Vergilio: Foundation Medicine: Current Employment; Roche: Current equity holder in publicly-traded company. Gana: Bausch: Current holder of individual stocks in a privately-held company; The Leukemia & Lymphoma Society: Consultancy. Druker: The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; Aileron: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Recludix Pharma, Inc.: Consultancy; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; Vincerx Pharma: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; GRAIL: Current equity holder in publicly-traded company; Iterion Therapeutics: Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; EnLiven: Consultancy, Research Funding; Merck & Co: Patents & Royalties; Pfizer: Research Funding; Nemucore Medical Innovations, Inc.: Consultancy; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees. Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees. Levine: Isoplexis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Zentalis: Membership on an entity's Board of Directors or advisory committees; Imago: Membership on an entity's Board of Directors or advisory committees; Ajax: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria; Prelude: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Consultancy; Celgene: Research Funding; Roche: Honoraria, Research Funding; Auron: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Astellas: Consultancy; Morphosys: Consultancy; QIAGEN: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Off-label use of entospletinib and decitabine.