North American ATLL has a distinct mutational and transcriptional profile and responds to epigenetic therapies.

Adult T-cell leukemia lymphoma (ATLL) is a rare T cell neoplasm that is endemic in Japanese, Caribbean, and Latin American populations. Most North American ATLL patients are of Caribbean descent and are characterized by high rates of chemo-refractory disease and worse prognosis compared with Japanese ATLL. To determine genomic differences between these 2 cohorts, we performed targeted exon sequencing on 30 North American ATLL patients and compared the results with the Japanese ATLL cases. Although the frequency of TP53 mutations was comparable, the mutation frequency in epigenetic and histone modifying genes (57%) was significantly higher, whereas the mutation frequency in JAK/STAT and T-cell receptor/NF-κB pathway genes was significantly lower. The most common type of epigenetic mutation is that affecting EP300 (20%). As a category, epigenetic mutations were associated with adverse prognosis. Dissimilarities with the Japanese cases were also revealed by RNA sequencing analysis of 9 primary patient samples. ATLL samples with a mutated EP300 gene have decreased total and acetyl p53 protein and a transcriptional signature reminiscent of p53-mutated cancers. Most importantly, decitabine has highly selective single-agent activity in the EP300-mutated ATLL samples, suggesting that decitabine treatment induces a synthetic lethal phenotype in EP300-mutated ATLL cells. In conclusion, we demonstrate that North American ATLL has a distinct genomic landscape that is characterized by frequent epigenetic mutations that are targetable preclinically with DNA methyltransferase inhibitors.

An applied test of the social learning theory of deviance to college alcohol use.

Several hypotheses about influences on college drinking derived from the social learning theory of deviance were tested and confirmed. The effect of ethnicity on alcohol use was completely mediated by differential association and differential reinforcement, whereas the effect of biological sex on alcohol use was partially mediated. Higher net positive reinforcements to costs for alcohol use predicted increased general use, more underage use, and more frequent binge drinking. Two unexpected finding were the negative relationship between negative expectations and negative experiences, and the substantive difference between nondrinkers and general drinkers compared with illegal or binge drinkers. The discussion considers implications for future campaigns based on Akers's deterrence theory.

(Mis)matched direct and moderating relationships among pro-environmental attitudes, environmental efficacy, and pro-environmental behaviors across and within 11 countries.

Pro-environmental behaviors are influenced by individuals' pro-environmental attitudes and environmental efficacy, among many other factors. However, attitude-behavior models are inconsistent on whether and how attitudes, efficacy, and behaviors should match in specificity or generality, and on the moderation effect of efficacy. This study first tests a simple model including direct and moderating relationships between pro-environmental attitudes, environmental efficacy, and pro-environmental behaviors. Then it examines relationships among subscales matched or mismatched in their respective specific or general domain of environmental attitudes (concern, values), environmental efficacy (self, collective), and pro-environmental behaviors (private, public). Secondary data come from an overall sample of 11,000 respondents across 11 countries, with n = 1,000 from each country. Pro-environmental attitudes and efficacy have direct relationships with pro-environmental behavior, but efficacy has little moderation effect. Different combinations of (mis)matched measures produce slightly different results, with the most variance explained, counter to hypotheses, by two mismatched models. Results are generally consistent across countries.

Myosin-driven rescue of contractile reserve and energetics in mouse hearts bearing familial hypertrophic cardiomyopathy-associated mutant troponin T is mutation-specific.

The thin filament protein troponin T (TnT) is a regulator of sarcomere function. Whole heart energetics and contractile reserve are compromised in transgenic mice bearing missense mutations at R92 within the tropomyosin-binding domain of cTnT, despite being distal to the ATP hydrolysis domain of myosin. These mutations are associated with familial hypertrophic cardiomyopathy (FHC). Here we test the hypothesis that genetically replacing murine αα-MyHC with murine ßß-MyHC in hearts bearing the R92Q cTnT mutation, a particularly lethal FHC-associated mutation, leads to sufficiently large perturbations in sarcomere function to rescue whole heart energetics and decrease the cost of contraction. By comparing R92Q cTnT and R92L cTnT mutant hearts, we also test whether any rescue is mutation-specific. We defined the energetic state of the isolated perfused heart using (31)P-NMR spectroscopy while simultaneously measuring contractile performance at four work states. We found that the cost of increasing contraction in intact mouse hearts with R92Q cTnT depends on the type of myosin present in the thick filament. We also found that the salutary effect of this manoeuvre is mutation-specific, demonstrating the major regulatory role of cTnT on sarcomere function at the whole heart level.

Sensemaking by Employees in Essential versus Non-essential Professions During the COVID-19 Crisis: A Comparison of Effects of Change Communication and Disruption Cues on Mental Health, Through Interpretations of Identity Threats and Work Meaningfulness.

This study examines the implications of categorizing workers into essential and non-essential groups due to disruptions in work associated with-and the quality of organizational change communication about-the COVID-19 pandemic. Specifically, we examine how these cues trigger identity threats and influence the meaningfulness of work, consequently affecting the mental health of workers (anxiety, distress, and depression). The results show that change communication reduces identity threat, while also increasing meaningfulness of work, for both work categories. However, the disruptions increase identity threat only for non-essential workers. Conversely, identity threat increases two of the three mental health issues while meaningfulness of work reduces two of them. The study contributes to our growing understanding of the pervasive, though subtle, implications of COVID-19 for the workplace by showing how a process of employee sensemaking and organizational change communication directly and indirectly influence important dimensions of mental health.

A review of the effects of uncertainty in public science communication.

Uncertainty is inherent to science and science communication. However, the evidence appears mixed regarding whether portraying uncertainty in science communication has positive or negative effects. We review a diverse range of experimental literature (k = 48; from 40 searches and 8000 retrievals), summarize the extant findings, and observe how the effects vary across four different types of communicated uncertainty (deficient, technical, scientific, and consensus uncertainty). The results indicate that most findings of negative effects (such as reduced credibility and beliefs) are from experiments that operationalized uncertainty as disagreement or conflict in science (consensus uncertainty). In this review, consensus uncertainty was never found to have positive effects. In contrast, uncertainty in the form of quantified error ranges and probabilities (technical uncertainty) in these studies has had only positive or null effects, not negative effects. We also highlight frequent moderators of the effects of uncertainty, such as prior beliefs and worldviews.

Influences, usage, and outcomes of Internet health information searching: multivariate results from the Pew surveys.

This paper provides results from seven major nationally representative datasets (two in detail) from the Pew Internet and American Life Project to answer two primary questions: (1) what influences people to seek online health information and (2) what influences their perceived outcomes from having access to this information? Cross-tabulations, logistic regressions, and multidimensional scaling are applied to these survey datasets. The strongest and most consistent influences on ever, or more frequently, using the Internet to search for health information were sex (female), employment (not fulltime), engaging in more other Internet activities, more specific health reasons (diagnosed with new health problem, ongoing medical condition, prescribed new medication or treatment), and helping another deal with health issues. Internet health seeking is consistently similar to general Internet activities such as email, news, weather, and sometimes hobbies. A variety of outcomes from or positive assessments of searching for Internet health information are predicted most strongly by sex (female), engaging in other Internet activities, Internet health information seeking including more frequent health seeking, more specific health reasons, belonging to an online support group sharing health interests, and helping another deal with an illness or major health condition.

Reducing STD/HIV stigmatizing attitudes through community popular opinion leaders in Chinese markets.

Reducing STDs and HIV/AIDS incidence requires campaigns designed to change knowledge, attitudes and practices of risky sexual behavior and its consequences. In China, a significant obstacle to such changes is the stigma associated with these diseases. Thus one campaign intervention strategy is to train credible community popular opinion leaders to discuss these issues in everyday social venues. This study tested the effectiveness of such an approach on reducing HIV/AIDS stigma, across two years, from a sample of over 4500 market vendors, in three conditions. Results showed an increasing growth in market communication about intervention messages, and concomitant declines in stigmatizing attitudes, across time, with the greatest changes in community popular opinion leaders, significant changes in intervention non-opinion leaders, and little change in the control markets.

Public views of mobile medical devices and services: a US national survey of consumer sentiments towards RFID healthcare technology.

A 2007 national public opinion survey of 1404 Americans revealed variations in sentiments concerning the desirability of several mobile healthcare technologies based on RFID. The survey appears to be the first reasonably national public opinion survey of US adults concerning their attitudes towards mobile healthcare technology. The survey revealed high levels of interest in emergency intervention services, but much less so in health information and monitoring services. Interest in RFID personal medical technology was positively associated with high levels of trust in others and social support. At the same time, a small minority were negatively disposed towards such applications. In those cases, the negative sentiment appears heightened when the mobile healthcare application is offered in a modality attached to the body as opposed to a somewhat more physically remote option, i.e., attached to one's cell phone.