Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in <i>RUNX1</i>, <i>GATA2</i>, and <i>DDX41</i>

Individuals with germ line variants associated with hereditary hematopoietic malignancies (HHMs) have a highly variable risk for leukemogenesis. Gaps in our understanding of premalignant states in HHMs have hampered efforts to design effective clinical surveillance programs, provide personalized preemptive treatments, and inform appropriate counseling for patients. We used the largest known comparative international cohort of germline RUNX1, GATA2, or DDX41 variant carriers without and with hematopoietic malignancies (HMs) to identify patterns of genetic drivers that are unique to each HHM syndrome before and after leukemogenesis. These patterns included striking heterogeneity in rates of early-onset clonal hematopoiesis (CH), with a high prevalence of CH in RUNX1 and GATA2 variant carriers who did not have malignancies (carriers-without HM). We observed a paucity of CH in DDX41 carriers-without HM. In RUNX1 carriers-without HM with CH, we detected variants in TET2, PHF6, and, most frequently, BCOR. These genes were recurrently mutated in RUNX1-driven malignancies, suggesting CH is a direct precursor to malignancy in RUNX1-driven HHMs. Leukemogenesis in RUNX1 and DDX41 carriers was often driven by second hits in RUNX1 and DDX41, respectively. This study may inform the development of HHM-specific clinical trials and gene-specific approaches to clinical monitoring. For example, trials investigating the potential benefits of monitoring DDX41 carriers-without HM for low-frequency second hits in DDX41 may now be beneficial. Similarly, trials monitoring carriers-without HM with RUNX1 germ line variants for the acquisition of somatic variants in BCOR, PHF6, and TET2 and second hits in RUNX1 are warranted

Media Multitasking and Cognitive, Psychological, Neural, and Learning Differences

American youth spend more time with media than any other waking activity: an average of 7.5 hours per day, every day. On average, 29% of that time is spent juggling multiple media streams simultaneously (ie, media multitasking). This phenomenon is not limited to American youth but is paralleled across the globe. Given that a large number of media multitaskers (MMTs) are children and young adults whose brains are still developing, there is great urgency to understand the neurocognitive profiles of MMTs. It is critical to understand the relation between the relevant cognitive domains and underlying neural structure and function. Of equal importance is understanding the types of information processing that are necessary in 21st century learning environments. The present review surveys the growing body of evidence demonstrating that heavy MMTs show differences in cognition (eg, poorer memory), psychosocial behavior (eg, increased impulsivity), and neural structure (eg, reduced volume in anterior cingulate cortex). Furthermore, research indicates that multitasking with media during learning (in class or at home) can negatively affect academic outcomes. Until the direction of causality is understood (whether media multitasking causes such behavioral and neural differences or whether individuals with such differences tend to multitask with media more often), the data suggest that engagement with concurrent media streams should be thoughtfully considered. Findings from such research promise to inform policy and practice on an increasingly urgent societal issue while significantly advancing our understanding of the intersections between cognitive, psychosocial, neural, and academic factors

Illusion and well-being: A social psychological perspective on mental health.

Many prominent theorists have argued that accurate perceptions of the self, the world, and the future are essential for mental health. Yet considerable research evidence suggests that overly positive selfevaluations, exaggerated perceptions of control or mastery, and unrealistic optimism are characteristic of normal human thought. Moreover, these illusions appear to promote other criteria of mental health, including the ability to care about others, the ability to be happy or contented, and the ability to engage in productive and creative work. These strategies may succeed, in large part, because both the social world and cognitive-processing mechanisms impose niters on incoming information that distort it in a positive direction; negative information may be isolated and represented in as unthreatening a manner as possible. These positive illusions may be especially useful when an individual receives negative feedback or is otherwise threatened and may be especially adaptive under these circumstances. Decades of psychological wisdom have established contact with reality as a hallmark of mental health. In this view, the well-adjusted person is thought to engage in accurate reality testing, whereas the individual whose vision is clouded by illusion is regarded as vulnerable to, if not already a victim of, mental illness. Despite its plausibility, this viewpoint is increasingly difficult to maintain (cf. Lazarus, 1983). A substantial amount of research testifies to the prevalence of illusion in normal human cognition (see Fiske&amp; Taylor, 1984; In this article, we review research suggesting that certain illusions may be adaptive for mental health and well-being. In particular, we examine evidence that a set of interrelated positive illusions-namely, unrealistically positive self-evaluations, exaggerated perceptions of control or mastery, and unrealistic optimism-can serve a wide variety of cognitive, affective, and social functions. We also attempt to resolve the following paraPreparation of this article was supported by National Science Foundation Grant BNS 83-08524, National Cancer Institute Grant CA 36409, and Research Scientist Development Award MH 00311 from the National Institute of Mental Health to Shelley E. Taylor. Jonathon D. Brown was supported by a University of California, Los Angeles, Chancellor&apos;s fellowship and by a Southern Methodist University new-faculty seed grant. We owe a great deal to a number of individuals who commented on earlier drafts: Nancy Cantor, Edward Emery, Susan Fiske, Tony Greenwald, Connie Hammen, Darrin Lehman, Chuck McClintock, Dick Nisbett, Lee Ross, Bill Swann, Joanne Wood, and two anonymous reviewers. Correspondence concerning this article should be addressed to Shelley E. Taylor, University of California, Department of Psychology, 405 Hilgard Avenue, Los Angeles, California 90024-1563. Our healthy individuals find it possible to accept themselves and their own nature without chagrin or complaint.. . . They can accept their own human nature with all of its discrepancies from the ideal image without feeling real concern. It would convey the wrong impression to say that they are self-satisfied. What we must rather say is that they can take the frailties and sins, weaknesses and evils of human nature in the same unquestioning spirit that one takes or accepts the characteristics of nature, (p. so that one is able to take in matters one wishes were different without distorting them to fit these wishes. (1953, p. 349) Since Jahoda&apos;s report, the position that the mentally healthy person perceives reality accurately has been put forth in major works by To summarize, then, although it is not the only theoretical perspective on the mentally healthy person, the view that psychological health depends on accurate perceptions of reality has been widely promulgated and widely shared in the literature on mental health. Social Cognition, Reality, and Illusion Early theorists in social cognition adopted a view of the person&apos;s information-processing capabilities that is quite similar to the viewpoint just described. These theorists maintained that the social perceiver monitors and interacts with the world like a naive scientist (see It rapidly became evident, however, that the social perceiver&apos;s actual inferential work and decision making looked little like these normative models. Rather, information processing is full of incomplete data gathering, shortcuts, errors, and biases (see At this point, we exchange the terms error and bias for a broader term, illusion. There are several reasons for this change in terminology. Error and bias imply short-term mistakes and distortions, respectively, that might be caused by careless oversight or other temporary negligences (cf. Funder, 1987). Illusion, in contrast, implies a more general, enduring pattern of error, bias, or both that assumes a particular direction or shape. As the evidence will show, the illusions to be considered (unrealistically positive self-evaluations, exaggerated perceptions of control, and unrealistic optimism) do indeed seem to be pervasive, enduring, and systematic. Illusion is denned as a perception that represents what is perceived in a way different from the way it is in reality. An illusion is a false mental image or conception which may be a misinterpretation of a real appearance or may be something imagined. It may be pleasing, harmless, or even useful (Stein, 1982, p. 662). The definition of an illusion as a belief that departs from reality presupposes an objective grasp of reality. This point puts us on the perilous brink of philosophical debate concerning whether one can ever know reality. Fortunately, at least to some degree, the methodologies of social psychology spare us this frustrating conundrum by providing operational definitions. In some cases, evidence for illusions comes from experimental work that manipulates feedback provided to a person (e.g., whether the person succeeded or failed on a task) and measures the individual&apos;s perceptions or recall of that feedback; this paradigm can provide estimates of an individual&apos;s accuracy as well as information about the direction (positive or negative) of any distortions. As will be seen, people typically distort such feedback in a self-serving manner. More subjective self-evaluations (e.g., how happy or well-adjusted one is) do not have these same objective standards of comparison. In such cases, an illusion is implied if the majority of people report that they are more (or less) likely than the majority of people to hold a particular belief. For example, if most people believe that they are happier, better adjusted, and more skilled on a variety of tasks than most other people, such perceptions provide evidence suggestive of an illusion. Illusions about the future are operationally difficult to establish because no one knows what the future will bring. If it can be shown, however, that most people believe that their future is more positive than that of most other people or more positive than objective baserate data can support, then evidence suggestive of illusions about the future is provided. We now turn to the evidence for these illusions. Positive Illusions and Social Cognition Any taxonomy of illusions is, to some extent, arbitrary. Many researchers have studied biases in the processing of self-relevant information and have given their similar phenomena different names. There is, however, considerable overlap in findings, and three that consistently emerge can be labeled unrealistically positive views of the self, exaggerated perceptions of personal control, and unrealistic optimism. Those familiar with the research evidence will recognize that much of the evidence for these positive illusions comes from experimental studies and from research with college students. We will have more to say about potential biases in the experimental literature later in this article. At present, it is important to note that all three of the ILLUSION AND WELL-BEING 195 illusions to be discussed have been documented in noncollege populations as well. Unrealistically Positive Views of the Self As indicated earlier, a traditional conception of mental health asserts that the well-adjusted individual possesses a view of the self that includes an awareness and acceptance of both the positive and negative aspects of self. In contrast to this portrayal, evidence indicates that most individuals possess a very positive view of the self (see Furthermore, the things that people are not proficient at are perceived as less important than the things that they are proficient at (e.g., In sum, far from being balanced between the positive and the negative, the perception of self that most individuals hold is heavily weighted toward the positive end of the scale. Of course, this imbalance does not in and of itself provide evidence that such views are unrealistic or illusory. Evidence of this nature is, however, available. First, there exists a pervasive tendency to see the self as better than others. Individuals judge positive personality attributes to be more descriptive of themselves than of the average person but see negative personality attributes as less descriptive of themselves than of the average person People also tend to use their positive qualities when appraising others, thereby virtually assuring a favorable self-other comparison Although the tendency to see the self as better than others is attenuated somewhat when the others being evaluated are close friends or relatives A second source of evidence pertaining to the illusory quality of positive self-perceptions comes from investigations in which self-ratings have been compared with judgments made by observers. In sum, the perception of self that most individuals hold is not as well-balanced as traditional models of mental health suggest. Rather than being attentive to both the favorable and unfavorable aspects of self, normal individuals appear to be very cognizant of their strengths and assets and considerably less aware of their weaknesses and faults. Evidence that these flattering self-portrayals are illusory comes from studies in which researchers have found that (a) most individuals see themselves as better than the average person and (b) most individuals se