The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery.

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.

Is the relationship of prosaccade reaction times and antisaccade errors mediated by working memory?

The mechanisms that control eye movements in the antisaccade task are not fully understood. One influential theory claims that the generation of antisaccades is dependent on the capacity of working memory. Previous research also suggests that antisaccades are influenced by the relative processing speeds of the exogenous and endogenous saccadic pathways. However, the relationship between these factors is unclear, in particular whether or not the effect of the relative speed of the pro and antisaccade pathways is mediated by working memory. The present study contrasted the performance of healthy individuals with high and low working memory in the antisaccade and prosaccade tasks. Path analyses revealed that antisaccade errors were strongly predicted by the mean reaction times of prosaccades and that this relationship was not mediated by differences in working memory. These data suggest that antisaccade errors are directly related to the speed of saccadic programming. These findings are discussed in terms of a race competition model of antisaccade control.

Negative affect and drinking drivers: a review and conceptual model linking dissonance, efficacy and negative affect to risk and motivation for change.

This review summarizes evidence on negative affect among drinking drivers. Elevations in negative affect, including depressed mood, anxiety and hostility, have long been noted in convicted drinking drivers, and recent evidence suggests an association between negative affect and driving after drinking in the general population. Previous efforts to understand the significance of this negative affective state have ranged from suggestions that it may play a causal role in drinking driving to suggestions that it may interfere with response to treatment and remedial interventions. Recent studies have uncovered an important paradox involving negative affect among convicted drinking drivers (hereafter DUI offenders). DUI offenders with high levels of negative affect recidivated more frequently following a DUI program than did those reporting no or minimal negative affect. However, when a brief supportive motivational intervention was added to the program, offenders with high negative affect levels showed lower recidivism rates than did those with no or minimal negative affect. The review includes studies from the general literature on alcohol treatment in which the same negative affect paradox was reported. In an attempt to understand this paradox, we present a conceptual model involving well-established psychological processes, with a focus on salient discrepancy, the crucial component of cognitive dissonance. In this model, negative affect plays an important role in motivating both continued high-risk drinking as well as therapeutic change. This model suggests that links between motivational states and negative affective processes may be more complex than previously thought. Implications for intervention with DUI offenders are discussed.

The effects of chemotherapy on Useful Field of View (UFOV) in younger and older breast cancer patients.

Chemotherapy is thought to cause cognitive deficits in some breast cancer patients, but the relative effects on older and younger breast cancer patients are unknown. The effects of chemotherapy on everyday cognitive tasks have not been examined. Thirty-eight female breast cancer survivors (3 to 45 months post chemotherapy) were compared to 55 age-matched control participants. Participants completed the Useful Field of View (UFOV), a computerized test of visual information processing that has been shown to decline with age, and which has been used to predict older adults' driving performance. Older chemotherapy patients performed more poorly than controls on the UFOV speed of processing, but not on the other two components. They also performed more poorly than younger chemotherapy patients. On the divided attention and selective attention components of the UFOV, older participants performed more poorly than younger participants, but there were no significant differences between chemotherapy patients and controls. These findings are explained in terms of brain changes thought to be caused by chemotherapy, which might have the most impact on older adults, already at risk for behavioral slowing.

Examining factors in the Research Institute on Addictions Self-Inventory (RIASI): Associations with alcohol use and problems at assessment and follow-up.

Impaired driving is a leading cause of alcohol-related deaths and injuries. Rehabilitation or remedial programs, involving assessment and screening of convicted impaired drivers to determine problem severity and appropriate programs, are an important component of society's response to this problem. Ontario's remedial program, Back on Track (BOT), involves an assessment process that includes administration of the Research Institute on Addictions Self-Inventory (RIASI) to determine assignment to an education or treatment program. The purpose of this study is to identify factors within the RIASI and examine how factor scores are associated with alcohol use and problem indicators at assessment and six-month follow-up. The sample included 22,298 individuals who completed BOT from 2000 to 2005. Principal component factor analysis with varimax rotation was conducted on RIASI data and an eight factor solution was retained: (1) Negative Affect, (2) Sensation Seeking, (3) Alcohol-Quantity, (4) Social Conformity, (5) High Risk Lifestyle, (6) Alcohol Problems, (7) Interpersonal Competence, and (8) Family History. Regression analyses were conducted to examine associations between factors and alcohol and problem measures obtained at assessment and at follow-up. Most factors, except for Interpersonal Competence, were associated with more alcohol use and problems at assessment. A similar pattern was observed at 6-month follow-up, but interestingly some factors (Negative Affect, Sensation Seeking, Alcohol-Quantity and Family History) predicted fewer days of alcohol use. The Interpersonal Competence factor was associated with significantly lower levels of alcohol use and problems at both assessment and follow-up. This work suggests that the RIASI provides information on several domains that have important relationships with alcohol problem severity and outcomes.

Examining the link between drinking-driving and depressed mood.

OBJECTIVE: Because both alcohol and depressed mood exert deleterious effects on psychomotor performance, the possibility that people with depressed mood may be more likely to drive after drinking may have important implications for traffic safety. In this work, we examine the association between depressed mood and self-reported driving after drinking in a large representative sample of adults in Ontario. METHOD: Data are based on the 2001-2004 Centre for Addiction and Mental Health Monitor, an ongoing cross-sectional telephone survey of Ontario adults ages 18 and older (N=3,979). Logistic regression analysis was performed to identify the risk of driving after drinking two or more drinks in the previous hour within the past 12 months associated with scores on a screening measure of depressed mood (depression-anxiety and social functioning subscales of the 12-item General Health Questionnaire), while controlling for alcohol-use measures (weekly volume and frequency of heavy drinking), driving exposure, and demographic factors. RESULTS: Logistic regression analysis revealed that the odds of reporting driving after drinking within the past year increase significantly as depressed mood (specifically, depression-anxiety scores) increases. CONCLUSIONS: Additional research on the nature of the link between depressed mood and impaired driving should be undertaken, including assessing whether there exists any synergistic effects of depressed mood and alcohol on collision risk and considering the implications of this relationship for prevention and remedial activities.

Oral health of young children in Mississippi Delta child care centers: a second look at early childhood caries risk assessment.

OBJECTIVES: To identify the predictors of early childhood caries and urgent dental treatment need among primarily African-American children in child care centers in the Delta region of Mississippi. The purpose of this study was to replicate predictors of caries and urgent dental treatment needs that were identified in an earlier study conducted in Delta child care centers and to assess additional caries risk factors not collected in the original study. METHODS: Children in 19 child care centers were examined by the dentists, and the parents provided data on oral health practices, oral health history, and on children's oral health-related quality of life (QOL). The dentists also assessed visible plaque and tested levels of mutans streptococci. Predictors of caries and treatment need among children 24 to 71 months of age were examined using logistic regression. RESULTS: Two parent predictors of caries identified in the earlier study (parent flossing and soft/sugary drink consumption) were not predictive in the current study. Parent history of abscess continued to predict their child's urgent need for treatment. Young children's level of salivary mutans streptococci, maxillary incisor visible plaque, and parents' reports of child oral health-related QOL measures predicted the presence of both caries and urgent treatment need. Some expected predictors, such as frequency of child's toothbrushing, were not predictive of caries. CONCLUSIONS: Parental abscess and parent's report of the child's oral health-related OOL are risk indicators for poor oral health outcomes that could be used by nondental personnel to identify young children in need of early preventive intervention and dental referral

The relationship between depressed mood, self-efficacy and affective states during the drinking driving sequence.

Relationships between depressed mood, abstinence confidence and temptation, and experienced emotions just before and during recent drinking driving sequences (drinking driving emotional states: DDES) were examined in a sample of DUI (Driving Under the Influence) offenders. Depressed mood offenders (41% of sample) reported lower abstinence confidence, higher temptation, and higher DDES, especially in association with negative affective states. Implications for interventions with depressed mood DUI offenders are discussed.

Court-mandated treatment for convicted drinking drivers.

Court-mandated treatment, which requires offenders convicted of alcohol or other drug-related crimes to participate in treatment for their substance abuse problems or face legal consequences, has long been a component of sanctioning for driving under the influence (DUI) and is a primary path of entry into alcoholism treatment for many people with problem drinking. Several issues are relevant to mandated treatment: screening, assessment and referral, effectiveness, DUI events as opportunities for intervention, brief interventions for offenders outside of mandated treatment, and cost-effectiveness of mandated treatment. Treatment effectiveness depends to some extent on offenders' motivation to participate, and offenders may resist treatment when their participation is coerced. Types of treatment such as motivational enhancement therapy may prove cost-effective with these involuntary participants. More research is needed into the changing DUI population, impaired driving and multidrug use, and new technologies for monitoring DUI offenders.

Oral health status of mississippi delta 3- to 5-year-olds in child care: an exploratory study of dental health status and risk factors for dental disease and treatment needs.

OBJECTIVES: For poor and minority young children, disparities exist in dental health and treatment. In rural impoverished areas, institutions that reach young children and potentially offer access to care are limited. In the current Mississippi Delta study, child care centers were examined as potential venues for oral health intervention and research, and potential risk factors for dental caries and treatment urgency in high-risk preschool children were explored. METHODS: Child care centers were selected and attending children recruited. Data on oral health practices were collected from surveys of center directors and parents/caregivers. Children were examined for caries and treatment urgency at centers by dentists. Bivariate and multivariate analyses with a 0. 05 alpha were used to examine data. RESULTS: A total of 346 preschool children at 15 participating centers were examined: 46% were female, 68% minority. Minority children and those with public insurance were more than twice as likely to have caries and urgent treatment needs as non-minorities or those with private insurance. The odds of children having caries were half as great if parents reported using floss and nearly twice as great if the parent had experienced a dental abscess. For every soft drink the parent consumed daily, the odds of dental caries for children increased by 44%. CONCLUSIONS: Conducting oral health exams and research in child care venues was possible, yet presented challenges. The combined use of two parental variables, reported soft drink consumption and abscess history, appears promising for caries prediction. Implementation of oral health programs and research in child care venues merits further exploration.

Are depressed drinking/driving offenders more receptive to brief intervention?

The relationship between depressed mood and interest in additional counseling was examined in three samples of adjudicated first DUI (drinking/driving) offenders who were participating in a court-mandated program. Based on prior research suggesting a relationship between depressed mood, higher motivation to change drinking and drinking/driving, and greater effectiveness of additional supportive brief intervention during the program, it was hypothesized that offenders expressing a depressed mood would be more receptive and less resistant to counseling than would offenders not expressing a depressed mood. In three sub-studies using several different measures of depressed mood, depressed mood was related to higher receptivity/lower resistance to counseling. Resistance rates were lowest for counseling that would occur within the program at no additional cost and highest when counseling required extra sessions or extra cost. Overall, Caucasian males were more resistant to counseling than were females or African-American males, although a differential relationship between depression and counseling resistance was not confirmed in comparisons of gender by ethnic groups.

The emergency care setting for screening and intervention for alcohol use problems among injured and high-risk drivers: a review.

Each year thousands of people are treated in emergency departments and trauma centers for alcohol-related injuries, including those sustained in drinking driving crashes. Emergency departments and trauma centers provide an opportunity to screen for alcohol use problems and intervene with injured or high-risk drivers to reduce future alcohol-related traffic and injury risk. Recently physicians have expressed interest in exploring screening and intervention for alcohol use problems in these venues as a means of improving clinical care. This article reviews the literature that has examined screening and brief interventions in acute care settings to reduce future alcohol consumption and alcohol-related injury. The methodological and practical issues inherent in conducting these studies as well as in actual practice are discussed. The chaotic environment of acute care, the large numbers of patients required to be screened to obtain an adequate study sample, and high attrition rates make study in these settings difficult at best and are methodological problems that should be addressed in future research. A basic question that has not been adequately answered by research to date is whether reduction in alcohol consumption will translate to reduced alcohol-related harm, such as driving while impaired, or injurious or fatal crashes. Long-term studies that assess records-based outcomes in addition to alcohol-consumption levels are needed.

A validity study of the Positive Psychology Protective Profile.

The purpose of this study was to conduct an exploratory factor analysis to provide support for the construct validity of the Positive Psychology Protective Profile, a self-report measure based on positive psychology. 985 undergraduates completed the profile, the Beck Depression Inventory, and the College Life Stress Inventory. Scores on the first two factor scores (Positive Outlook, Negative Symptoms) for the profile correlated significantly with scores on depression and stress, whereas scores on the third profile factor (Problem-solving) correlated significantly only with scores on the Beck Depression Inventory. Scores on the Positive Outlook significantly differentiated participants having either chronic illness or recent major illness from those who did not.

An exploratory study of the relationship between road rage and crash experience in a representative sample of US drivers.

The phenomenon of road rage has been frequently discussed but infrequently examined. Using a representative sample of 1382 US adult drivers, who were interviewed in a 1998 telephone survey, exploratory analyses examined the relationship between self-reported measures of road rage, generally hazardous driving behaviors, and crash experience. Regarding specific road rage behaviors, most respondents reported having engaged in verbal expressions of annoyance; however only 2.45% reported ever having been involved in direct confrontation with another car or driver. After controlling for gender, age. driving frequency, annual miles driven and verbal expression, an angry/threatening driving subscale of road rage was significantly associated with hazardous driving behaviors that included frequency of driving over the legal blood alcohol limit, receipt of tickets in the past year. and habitually exceeding the speed limit as well as crash experience. However, the verbal/frustration expression subscale was not associated with crash experience or hazardous driving indicators, except for number of tickets, after controlling for other crash-related factors such as gender and age. Direct confrontation by deliberately hitting another car or leaving the car to argue with and/or injure another driver was rarely reported. Results suggest that angry/threatening driving is related to crash involvement; however, after controlling for exposure and angry/threatening and hazardous driving the relationship of milder expressions of frustration while driving and crash involvement was not significant.

Enhancing the effectiveness of traditional interventions with drinking drivers by adding brief individual intervention components.

OBJECTIVE: The purpose of the research was to determine whether the effectiveness of a traditional DUI (Driving Under the Influence) group intervention program could be enhanced by the addition of two brief individual intervention sessions and a follow-up. The differential effectiveness of the individual intervention component was examined for four offender subgroups (young minorities, problem drinkers, women and depressed offenders) that had been previously identified as at high risk or vulnerable. METHOD: Adjudicated first DUI offenders (N = 4,074), of whom 776 (19%) were female, were randomly assigned to a standard first-offender program or an enhanced standard program that included two short individual sessions and a brief follow-up session. The setting was a mandated first-offender program in 10 Mississippi locations. RESULTS: Depressed offenders who were assigned to the enhanced program were 35% less likely to recidivate than those assigned to the standard program. The effectiveness of the two programs did not differ significantly for offenders who self-reported low depression. No significant interaction effects were found between program type and age, minority status or gender. After depressed mood was controlled for, problem-drinker status was not related to program effectiveness; however, problem drinkers had higher depression rates. CONCLUSIONS: Results suggest that the combination of a standard first-offender program with brief individual counseling can be effective for DUI offenders who report depressed mood and who are at high risk for recidivism. A five-item screen for sad/depressed mood from a widely used DUI risk assessment instrument identified offenders who benefited from the enhanced intervention.

Mandated Treatment: Lessons From Research With Drinking and Driving Offenders.

Institutions, such as the courts, have been mandating referrals to alcoholism treatment with increasing frequency in recent decades. Because of this trend, defining the differences between mandated and voluntary treatment goals and effectiveness has become more important.