Members of the nuclear factor-κB (NF-κB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-κB signalling is present in most ...human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-κB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-κB signalling, and an uncharacterized gene, C11orf95. In each case, C11orf95-RELA fusions resulted from chromothripsis involving chromosome 11q13.1. C11orf95-RELA fusion proteins translocated spontaneously to the nucleus to activate NF-κB target genes, and rapidly transformed neural stem cells--the cell of origin of ependymoma--to form these tumours in mice. Our data identify a highly recurrent genetic alteration of RELA in human cancer, and the C11orf95-RELA fusion protein as a potential therapeutic target in supratentorial ependymoma.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite evidence that parents’ physical aggression abuse has long-lasting negative consequences, information about the true population prevalence of aggression and physical abuse is limited. We have ...even less information about how parental aggression and abuse vary by child age, parent gender, and how that aggression and abuse might be clustered within families. To address these gaps, an anonymous, computer-based assessment was administered to nearly 40,000 parents of more than 60,000 children in the United States Air Force, which included a detailed assessment on up to four minor children of aggression and its impact. The survey was the largest of its type ever conducted in the United States, allowing for stable, crossvalidated estimation of rates of both corporal punishment and physical abuse. Approximately 39% of children experienced corporal punishment, peaking at three years of age, and 7% experienced physical abuse, peaking at age six. About 45% of parents reported perpetrating corporal punishment and 8% abuse; these rates were higher in multi-child families and most often involved more than one child. Parent gender was not associated with physical aggression or abuse.
Excessive gambling can cause substantial biopsychosocial problems (e.g., difficulties with finances, relationships, mental, and physical health). For military Service Members, it can also result in ...security clearance denial or revocation, failure to achieve promotions, and premature career termination. Recent congressional mandates have obligated the U.S. Department of Defense to screen for problematic gambling, the predictive values of which are a function of (i) problem prevalence and (ii) tool sensitivity and specificity. This meta-review (i.e., systematic review of systematic reviews) on the screening properties of gambling assessment tools and the effectiveness of treatments for gambling disorder is to inform military services on responding to Service Members' gambling problems.
EBSCO Discovery Service, PubMed, PsycINFO, Ovid Medline, Social Care Online, Epistemonikos, International Health Technology Assessment, and the Cochrane Central Register of Controlled Trials electronic databases were searched up to December 2022 for systematic reviews and meta-analyses on measurements of adult subclinical or gambling, and interventions targeting individuals with GD. Three and four studies were included in each section of the current meta-review (i.e., assessment tools and treatment). For review 1, the estimated risk of bias was assessed using the Risk of Bias in Systematic Reviews.
Thirty-one tools were identified through the three systematic reviews. All had modest sensitivities and specificities; combined with low prevalences in the general SM population, positive results would be incorrect 64-99% of the time. However, if screening were conducted with SMs referred for alcohol problems, a positive result on the best screening tools would be correct 76% of the time. Several commonly used treatment approaches had demonstrated efficacy for GD.
The combination of low prevalence of GD and subclinical gambling problems in the general population, coupled with modest sensitivity and specificity, makes screening unfeasible in the general SM population. However, dual-phase screening in higher-prevalence subpopulations (i.e., SMs already identified with substance-abuse or mental-health problems) would be viable. Regarding treatment, several interventions-already used in military healthcare-with extensive empirical track records have been successfully used to treat adults with GD.
This study investigates associations between (a) relationship satisfaction and intimate partner violence (IPV: psychological, physical, and sexual) and (b) observed couple communication behavior. ...Mixed-sex couples (N = 291) were recruited via random digit dialing. Partners completed the Quality of Marriage Index (Norton, 1983), the Revised Conflict Tactics Scale (Straus et al., 1996), and one female-initiated and one male-initiated 10-min conflict conversations. Discussions were coded with Rapid Marital Interaction Coding System, 2nd Generation (Heyman et al., 2015). As hypothesized, lower satisfaction was associated with more hostility (p =.018) and less positivity (p < .001); more extensive IPV was associated with more hostility (p < .001). For negative reciprocity, there was a dissatisfaction × IPV extent × conversation-initiator interaction (p < .006). Results showed that conflict behaviors of mixed-sex couples are related to the interplay among gender, satisfaction, and the severity of couple-level IPV. Theoretical and clinical implications are discussed.
To inform interpersonal models of intimate partner violence (IPV), the present study examines patterns of vocally encoded emotional arousal during the conversations of mixed-gender couples who ...reported on the extent of physical and psychological IPV and degree of relationship satisfaction (N = 149). All couples completed two problem-solving discussions. Emotional arousal was measured continuously during each conversation using vocal fundamental frequency. Contrary to expectations, results demonstrated that trajectories of arousal differed based on gender, IPV, and relationship satisfaction. Within conversations, men demonstrated linear increases in arousal at higher levels of IPV, suggesting that men may either struggle to contain their emotions or use heightened emotional expression as a conflict strategy in relationships with more extensive IPV. Conversely, women exhibited different trajectories of arousal depending on the combinations of relationship satisfaction and couple IPV, except at higher levels of their own satisfaction. Specifically, when women reported being highly satisfied in their relationships, they demonstrated similarly shaped trajectories across all levels of IPV and men's satisfaction. Together, this suggests that women's higher relationship satisfaction may buffer their emotional expression, although this may not always be adaptive within the context of relationships with extensive IPV. Overall, this study offers insight into the dynamic interpersonal processes linked with relationship distress and IPV and implies the need for a more nuanced, interpersonal research agenda for IPV research.
In this study, the authors assessed men's and women's partner and parent physical aggression among 453 representatively sampled families with young children. The prevalences of partner aggression and ...of severe parent aggression were higher than previously reported. Substantial rates of co-occurrence were found. Risk ratios and regression analyses indicated that connections between (a) husbands' and wives' partner aggression and (b) mothers' and fathers' parent aggression were especially strong. Patterns of co-occurrence pointed to the probable relative importance of family-level, in comparison with individual, predictors of aggression. Patterns of co-occurring violence are described in light of the theoretical literature. Implications for studying family violence in community samples are discussed.
Aβ25–35 is a short, cytotoxic, and naturally occurring fragment of the Alzheimer’s Aβ peptide. To map the molecular mechanism of Aβ25–35 binding to the zwitterionic dimyristoylphosphatidylcholine ...(DMPC) bilayer, we have performed replica exchange with solute tempering molecular dynamics simulations using all-atom explicit membrane and water models. Consequences of sequence truncation on the binding mechanism have been measured by utilizing as a control our previous simulations probing binding of the longer peptide Aβ10–40 to the same bilayer. The most intriguing feature of Aβ25–35 binding to the DMPC bilayer is a coexistence of two bound states with strikingly different characteristics: a dominant surface-bound state and a less stable inserted state. In the surface-bound state, the peptide samples extended conformations, in which its unbound C-terminal is pointed away from the bilayer. In contrast, in the inserted state, the C-terminal resides deep in the bilayer hydrophobic core. In both states, the N-terminal remains anchored to the bilayer. Free energy landscape analysis reveals that the two states are separated by a moderate barrier, suggesting that Aβ25–35 monomer may frequently interconvert between them. The net effect of Aβ25–35 binding is a minor impact on the bilayer structure, which contrasts with the considerable bilayer perturbations induced by a longer Aβ10–40 peptide penetrating deep into the bilayer core. Therefore, we conclude that the binding mechanisms of Aβ25–35 and Aβ10–40 peptides are different. Potential implications of our results for Aβ25–35 cytotoxicity are discussed. A comparison of experimental data with our findings reveals a good agreement.
This article examines some important legal developments, as well as corporate strategies, that have occurred as a result of recent movements initiated by U.S. workers, such as #MeToo, Time's Up, and ...others. It also includes a RESPECT checklist of business strategies to assist in improving corporate culture and climate. Keywords: #MeToo movement, cultural movements, corporate culture, entertainment business culture, employment disputes, contract law, confidentiality provisions, non-disclosure agreements, alternative dispute resolution, gender pay disparity, corporate best practices
Two studies examined the impact of the implementation of the Field-tested Assessment, Intervention-planning, and Response (FAIR) system, a system-level intervention for determining whether ...allegations of family maltreatment meet threshold for abuse or neglect, on alleged recidivism. Data were collected at the 10 U.S. Army installations with the largest family maltreatment caseloads. Participants were family members who had an allegation of family maltreatment (i.e., child maltreatment or partner abuse) during one of the two study periods. Data were collected when Family Advocacy Program staff used the then-in-place system (Case Review Committee) and later the FAIR system. In Study 1, cases were followed for 6 months following the initial maltreatment allegation to measure the occurrence of subsequent allegations of any type. Additionally, at five installations, alleged victims of partner abuse were recruited into a study (Study 2) in which they anonymously reported on intimate partner violence via telephone. In Study 1, the advantage for the FAIR condition was concentrated in cases with unsubstantiated initial determinations; the mean relative risk reduction for recidivism was 0.48. In Study 2, FAIR extended median time to recidivism by approximately 170%. These results replicate and extend earlier findings that employing the FAIR system can result in decreased family maltreatment re-offense.
We address the following questions that are becoming increasingly important to managers in service industries: Are the levels of customer satisfaction and loyalty for the same service different when ...customers choose the service online versus offline? If yes, what factors might explain these differences? How is the relationship between customer satisfaction and loyalty in the online environment different from that in the offline environment? We propose a conceptual framework and develop hypotheses about the effects of the online medium on customer satisfaction and loyalty and on the relationships between satisfaction and loyalty. We test the hypotheses through a simultaneous equation model using two data sets of online and offline customers of the lodging industry. The results are somewhat counterintuitive in that they show that whereas the levels of customer satisfaction for a service chosen online is the same as when it is chosen offline, loyalty to the service provider is higher when the service is chosen online than offline. We also find that loyalty and satisfaction have a reciprocal relationship such that each positively reinforces the other, and this relationship between overall satisfaction and loyalty is further strengthened online.
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