HIF-2α expression and metabolic signaling require ACSS2 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an aggressive cancer driven by VHL loss and aberrant HIF-2α signaling. Identifying means to regulate HIF-2α thus has potential therapeutic benefit. Acetyl-CoA synthetase 2 (ACSS2) converts acetate to acetyl-CoA and is associated with poor patient prognosis in ccRCC. Here we tested the effects of ACSS2 on HIF-2α and cancer cell metabolism and growth in ccRCC models and clinical samples. ACSS2 inhibition reduced HIF-2α levels and suppressed ccRCC cell line growth in vitro, in vivo, and in cultures of primary ccRCC patient tumors. This treatment reduced glycolytic signaling, cholesterol metabolism, and mitochondrial integrity, all of which are consistent with loss of HIF-2α. Mechanistically, ACSS2 inhibition decreased chromatin accessibility and HIF-2α expression and stability. While HIF-2α protein levels are widely regulated through pVHL-dependent proteolytic degradation, we identify a potential pVHL-independent pathway of degradation via the E3 ligase MUL1. We show that MUL1 can directly interact with HIF-2α and that overexpression of MUL1 decreased HIF-2α levels in a manner partially dependent on ACSS2. These findings identify multiple mechanisms to regulate HIF-2α stability and ACSS2 inhibition as a strategy to complement HIF-2α-targeted therapies and deplete pathogenically stabilized HIF-2α.

Suppression of TCF4 promotes a ZC3H12A-mediated self-sustaining inflammatory feedback cycle involving IL-17RA/IL-17RE epidermal signaling.

IL-17C is an epithelial cell-derived proinflammatory cytokine whose transcriptional regulation remains unclear. Analysis of the IL17C promoter region identified TCF4 as putative regulator, and siRNA knockdown of TCF4 in human keratinocytes (KCs) increased IL17C. IL-17C stimulation of KCs (along with IL-17A and TNF-α stimulation) decreased TCF4 and increased NFKBIZ and ZC3H12A expression in an IL-17RA/RE-dependent manner, thus creating a feedback loop. ZC3H12A (MCPIP1/Regnase-1), a transcriptional immune-response regulator, also increased following TCF4 siRNA knockdown, and siRNA knockdown of ZC3H12A decreased NFKBIZ, IL1B, IL36G, CCL20, and CXCL1, revealing a proinflammatory role for ZC3H12A. Examination of lesional skin from the KC-Tie2 inflammatory dermatitis mouse model identified decreases in TCF4 protein concomitant with increases in IL-17C and Zc3h12a that reversed following the genetic elimination of Il17c, Il17ra, and Il17re and improvement in the skin phenotype. Conversely, interference with Tcf4 in KC-Tie2 mouse skin increased Il17c and exacerbated the inflammatory skin phenotype. Together, these findings identify a role for TCF4 in the negative regulation of IL-17C, which, alone and with TNF-α and IL-17A, feed back to decrease TCF4 in an IL-17RA/RE-dependent manner. This loop is further amplified by IL-17C-TCF4 autocrine regulation of ZC3H12A and IL-17C regulation of NFKBIZ to promote self-sustaining skin inflammation.

Standards for the care of people with cystic fibrosis (CF); recognising and addressing CF health issues.

This is the third in a series of four papers updating the European Cystic Fibrosis Society (ECFS) standards for the care of people with CF. This paper focuses on recognising and addressing CF health issues. The guidance was produced with wide stakeholder engagement, including people from the CF community, using an evidence-based framework. Authors contributed sections, and summary statements which were reviewed by a Delphi consultation. Monitoring and treating airway infection, inflammation and pulmonary exacerbations remains important, despite the widespread availability of CFTR modulators and their accompanying health improvements. Extrapulmonary CF-specific health issues persist, such as diabetes, liver disease, bone disease, stones and other renal issues, and intestinal obstruction. These health issues require multidisciplinary care with input from the relevant specialists. Cancer is more common in people with CF compared to the general population, and requires regular screening. The CF life journey requires mental and emotional adaptation to psychosocial and physical challenges, with support from the CF team and the CF psychologist. This is particularly important when life gets challenging, with disease progression requiring increased treatments, breathing support and potentially transplantation. Planning for end of life remains a necessary aspect of care and should be discussed openly, honestly, with sensitivity and compassion for the person with CF and their family. CF teams should proactively recognise and address CF-specific health issues, and support mental and emotional wellbeing while accompanying people with CF and their families on their life journey.

Do different sit-stand workstations influence lumbar kinematics, lumbar muscle activity and musculoskeletal pain in office workers? A secondary analysis of a randomized controlled trial.

Purpose. This study investigated the effect of different sit-stand workstations on lumbar spine kinematics, lumbar muscle activity and musculoskeletal pain. Methods. Thirty-two office workers were randomized to one of three sit-stand workstations (Group 1, ratio of minutes spent sitting to standing each hour at work 40:20, n = 8; Group 2, 30:30, n = 6; Group 3, 20:40, n = 7) and a control group (usual sitting, n = 11). Intervention groups (Groups 1, 2 and 3) were collapsed into one group for analysis (n = 21). Data on lumbar kinematics and muscle activity were only collected for 25 participants due to equipment availability. Results. Participants in the intervention group had lower overall lumbar spine flexion angles during the workday compared to the control group (mean difference 10.6°; 95% confidence interval [-18.1, -3.2]; p = 0.008; Cohen's d = 1.5). There were no between-group differences for the remaining kinematic measures (i.e., mean flexion angle in standing and sitting, mean side flexion angle in standing and sitting, and percentage of time in upright sitting), muscle activity or presence of musculoskeletal pain. Conclusions. Sit-stand workstations reduced overall lumbar spine flexion angles over the course of a workday but had no effect on other kinematic measures, lumbar spine muscle activity or musculoskeletal pain.Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12615001018505..

Do schizotypy features predict cannabis problems in partnered community adults?

Schizotypy and its associated features-negative schizotypy, disorganization, and positive schizotypy-are correlated with increased cannabis use. Yet, it is unclear whether cannabis users with schizotypy are at greater risk of developing cannabis problems. Individuals with elevated schizotypy may be particularly vulnerable to cannabis problems. It is important to understand this association given the unknown harms of chronic cannabis use. Data for these analyses were drawn from a larger investigation of cannabis use in adult romantic relationships. Participants were community adults (N = 366; M Age = 24.6, SD = 3.1) who reported regular use of cannabis. Participants completed baseline surveys measuring cannabis use frequency, problems, and schizotypy. Follow-up assessments of cannabis problems and frequency were completed 4-, 7- and 10-months post-baseline. Multiple regression was used to test the effect of schizotypy-measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B, Raine & Benishay, 1995)-on cannabis use problems controlling for 30-day cannabis use. At baseline, disorganization and positive schizotypy were associated with cannabis use, primarily for women. Results revealed that with cannabis use frequency in the model, the Disorganization subscale of the SPQ-B predicted cannabis problems at baseline and all 3 follow-up assessments. Results are consistent with research suggesting that those exhibiting odd behaviors report more problematic cannabis use. Future research may further this line of inquiry with a focus on longitudinal, reciprocal relationships among schizotypy features, cannabis use, and cannabis problems.

Polyploid Hepatocytes Facilitate Adaptation and Regeneration to Chronic Liver Injury.

The liver contains diploid and polyploid hepatocytes (tetraploid, octaploid, etc.), with polyploids comprising ≥90% of the hepatocyte population in adult mice. Polyploid hepatocytes form multipolar spindles in mitosis, which lead to chromosome gains/losses and random aneuploidy. The effect of aneuploidy on liver function is unclear, and the degree of liver aneuploidy is debated, with reports showing aneuploidy affects 5% to 60% of hepatocytes. To study relationships among liver polyploidy, aneuploidy, and adaptation, mice lacking E2f7 and E2f8 in the liver (LKO), which have a polyploidization defect, were used. Polyploids were reduced fourfold in LKO livers, and LKO hepatocytes remained predominantly diploid after extensive proliferation. Moreover, nearly all LKO hepatocytes were euploid compared with control hepatocytes, suggesting polyploid hepatocytes are required for production of aneuploid progeny. To determine whether reduced polyploidy impairs adaptation, LKO mice were bred onto a tyrosinemia background, a disease model whereby the liver can develop disease-resistant, regenerative nodules. Although tyrosinemic LKO mice were more susceptible to morbidities and death associated with tyrosinemia-induced liver failure, they developed regenerating nodules similar to control mice. Analyses revealed that nodules in the tyrosinemic livers were generated by aneuploidy and inactivating mutations. In summary, we identified new roles for polyploid hepatocytes and demonstrated that they are required for the formation of aneuploid progeny and can facilitate adaptation to chronic liver disease.

Does morning affect contribute to daily Cannabis use?

Several theories posit that cannabis and other substances are used to reduce negative affect. This daily report study considered whether variations in positive and negative affect, reported each morning, contributed to the likelihood of cannabis use later that day. We also explored whether levels of positive and negative affect reported immediately after cannabis use improved, relative to that day's morning levels. The sample included 183 men and 183 women representing heterosexual, cannabis-using couples from the community. Participants made independent, daily reports of affect and cannabis use episodes for 30 consecutive days. Using multilevel modeling, we modeled men's and women's use of cannabis on a given day as a function of morning levels of positive, hostile, and anxious affect, accounting for partner cannabis use that day, and mean levels of positive and negative affect. Men and women were more likely to use cannabis on a given day when morning positive affect was lower than typical for the person and when partner used cannabis that day. Neither hostile nor anxious affect contributed to later use of cannabis. Immediately after cannabis use, positive affect increased, and hostile and anxious affect decreased relative to that day's morning levels. The improved affect immediately after use suggests a mechanism of positive reinforcement.

Examining cannabis protective behavioral strategy use using multiple methods.

PURPOSE ­: Cannabis use among young adults is increasing, despite being associated with several negative consequences. Protective behavioral strategies (PBSs) are a potential mechanism of behavior change for reducing substance use, yet PBS use for cannabis is not well understood. The purpose of this paper is to further define and measure the PBS construct for cannabis. DESIGN/METHODOLOGY/APPROACH ­: A community sample of cannabis users (n = 54) participated in eight focus groups discussing the use of PBSs. Participants completed surveys regarding demographics, cannabis use habits and cannabis problems. The authors also administered an existing measure of cannabis PBS and asked them to generate new or unique protective strategies that they had used or had heard of others using. FINDINGS ­: Thematic analysis of qualitative focus group data provided information about cannabis users' reasons for regulating cannabis use (e.g. health or legal problems, interpersonal) as well as strategies to moderate cannabis use or attenuate their risk for experiencing adverse consequences (e.g. distraction, existential/spiritual strategies). Analyses of quantitative survey data revealed that use of PBSs was negatively correlated with cannabis outcomes. Perceived helpfulness of strategies was an important predictor of decreased cannabis use and adverse consequences. RESEARCH LIMITATIONS/IMPLICATIONS ­: Findings expand the understanding of the definition and measurement of strategies for regulating cannabis use and reducing related risk of experiencing adverse consequences. ORIGINALITY/VALUE ­: This is the first study to examine cannabis-related PBS using both qualitative and quantitative methods, which provide insights into the definition of PBS and for future refinements of PBS measurement.

Histone deacetylase inhibitor treatment induces postpartum-like maternal behavior and immediate early gene expression in the maternal neural pathway in virgin mice.

The peripartum period is associated with the onset of behaviors that shelter, feed and protect young offspring from harm. The neural pathway that regulates caregiving behaviors has been mapped in female rats and is conserved in mice. However, rats rely on late gestational hormones to shift their perception of infant cues from aversive to attractive, whereas laboratory mice are "spontaneously" maternal, but their level of responding depends on experience. For example, pup-naïve virgin female mice readily care for pups in the home cage, but avoid pups in a novel environment. In contrast, pup-experienced virgin mice care for pups in both contexts. Thus, virgin mice rely on experience to shift their perception of infant cues from aversive to attractive in a novel context. We hypothesize that alterations in immediate early gene activation may underlie the experience-driven shift in which neural pathways (fear/avoidance versus maternal/approach) are activated by pups to modulate context-dependent changes in maternal responding. Here we report that the effects of sodium butyrate, a drug that allows for an amplification of experience-induced histone acetylation and gene expression in virgins, are comparable to the natural onset of caregiving behaviors in postpartum mice and induce postpartum-like patterns of immediate early gene expression across brain regions. These data suggest that pups can activate a fear/defensive circuit in mice and experience-driven improvements in caregiving behavior could be regulated in part through decreased activation of this pathway.

Do Men Use More Sexually Aggressive Tactics When Intoxicated? A Within-Person Examination of Naturally Occurring Episodes of Sex.

OBJECTIVE: Men's alcohol use has been linked to sexual assault perpetration. Yet, it is unknown whether within naturally-occurring sexual encounters men use more sexually aggressive tactics when they are intoxicated. The present study considered whether college men's perceived intoxication at the time of sex increased their self-reported use of verbal persuasion, physical force, and encouraged intoxication of partner as tactics to convince a woman to have sex. METHOD: As part of a 56-day daily report study, 298 college freshman males reported 1,832 episodes of sexual activity with female partners. Using multilevel modeling, we considered the within-person effects of subjective intoxication, sexual precedence (new versus previous partner), and perceived partner sexual interest on male use of sexually aggressive strategies within each sexual encounter. We also considered whether the impact of event-specific intoxication was moderated by individual differences in hostility toward women, delinquency, and impersonal sex. RESULTS: Greater subjective intoxication at the time of sex predicted greater use of verbal persuasion and encouraging intoxication of partner. Although intoxication did not predict physical force directly, there were indirect effects via greater verbal persuasion and encouraging partner intoxication. Event-specific intoxication did not interact with any of the individual difference variables and only hostility toward women contributed positively to use of event-specific sexually aggression. CONCLUSIONS: Men's intoxication at the time of sexual activity increases their use of sexually aggressive strategies within naturally-occurring sexual encounters. Findings help to explain the robust relationship between alcohol use and sexual assault found in college populations.

Emotion regulation difficulties and social control correlates of smoking among pregnant women trying to quit.

Approximately 15% of US women currently smoke during pregnancy. An important step toward providing effective smoking cessation interventions during pregnancy is to identify individuals who are more likely to encounter difficulty quitting. Pregnant smokers frequently report smoking in response to intrapersonal factors (e.g., negative emotions), but successful cessation attempts can also be influenced by interpersonal factors (i.e., influence from close others). This study examined the association between emotion regulation difficulties, positive and negative social control (e.g., encouragement, criticism), and smoking cessation-related variables (i.e., smoking quantity, withdrawal symptoms) among pregnant smokers. Data were drawn from the pretreatment wave of a smoking cessation trial enrolling low-income pregnant women who self-reported smoking in response to negative affect (N = 73). Greater emotion regulation difficulties were related to greater smoking urges (b = 0.295, p = .042) and withdrawal symptoms (b = 0.085, p = .003). Additionally, more negative social control from close others was related to fewer smoking days (b = -0.614, p = .042) and higher smoking abstinence self-efficacy (b = 0.017, p = .002). More positive social control from close others interacted with negative affect smoking (b = -0.052, p = .043); the association between negative affect smoking and nicotine dependence (b = 0.812, p < .001) only occurred at low levels of positive social control. Findings suggest that emotion regulation difficulties may contribute to smoking during pregnancy by exacerbating women's negative experiences related to smoking cessation attempts. Negative social control was related to lower smoking frequency and greater confidence in quitting smoking, suggesting that it may assist pregnant smokers' cessation efforts. Positive social control buffered women from the effects of negative affect smoking on nicotine dependence. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01163864.

The Polyploid State Restricts Hepatocyte Proliferation and Liver Regeneration in Mice.

The liver contains a mixture of hepatocytes with diploid or polyploid (tetraploid, octaploid, etc.) nuclear content. Polyploid hepatocytes are commonly found in adult mammals, representing ~90% of the entire hepatic pool in rodents. The cellular and molecular mechanisms that regulate polyploidization have been well characterized; however, it is unclear whether diploid and polyploid hepatocytes function similarly in multiple contexts. Answering this question has been challenging because proliferating hepatocytes can increase or decrease ploidy, and animal models with healthy diploid-only livers have not been available. Mice lacking E2f7 and E2f8 in the liver (liver-specific E2f7/E2f8 knockout; LKO) were recently reported to have a polyploidization defect, but were otherwise healthy. Herein, livers from LKO mice were rigorously characterized, demonstrating a 20-fold increase in diploid hepatocytes and maintenance of the diploid state even after extensive proliferation. Livers from LKO mice maintained normal function, but became highly tumorigenic when challenged with tumor-promoting stimuli, suggesting that tumors in LKO mice were driven, at least in part, by diploid hepatocytes capable of rapid proliferation. Indeed, hepatocytes from LKO mice proliferate faster and out-compete control hepatocytes, especially in competitive repopulation studies. In addition, diploid or polyploid hepatocytes from wild-type (WT) mice were examined to eliminate potentially confounding effects associated with E2f7/E2f8 deficiency. WT diploid cells also showed a proliferative advantage, entering and progressing through the cell cycle faster than polyploid cells, both in vitro and during liver regeneration (LR). Diploid and polyploid hepatocytes responded similarly to hepatic mitogens, indicating that proliferation kinetics are unrelated to differential response to growth stimuli. Conclusion: Diploid hepatocytes proliferate faster than polyploids, suggesting that the polyploid state functions as a growth suppressor to restrict proliferation by the majority of hepatocytes.

Alcohol and Marijuana use in Undergraduate Males: Between- and Within-Person Associations with Interpersonal Conflict.

BACKGROUND: Among college students, interpersonal conflict with others is a common, yet stressful negative interpersonal experience. Research suggests that drinking episodes may contribute to the occurrence of conflict. Marijuana use, independently or in conjunction with alcohol, may also influence the likelihood of subsequent conflict. OBJECTIVES: We considered the temporal effects of independent and simultaneous alcohol and marijuana use episodes on the occurrence of interpersonal conflict. Use of multilevel modeling allowed us to distinguish the within-person effects of substance use from between-person differences in frequency of use. METHODS: Within a sample of 427 college freshman males over 56 days of daily reports, we examined the independent and interactive effects of episodes of alcohol and marijuana on the odds of conflict within the next 1-, 2-, 3-, and 4 hours. RESULTS: Multilevel modeling analyses showed that drinking episodes increased the likelihood of conflict occurring within the next 1, 2, 3, and 4 hours. Marijuana had weaker positive effects, significant only within the 2 hour window. There were no alcohol by marijuana interaction effects in any analysis. CONCLUSIONS/IMPORTANCE: Both marijuana and alcohol independently increased the likelihood of interpersonal conflict; however, the marijuana effect appeared less robust. As marijuana use becomes more normative and accessible for college students, it is important to understand the extent to which marijuana use results in negative consequences and the contexts under which these effects unfold.

Does Marijuana Contribute to Intimate Partner Aggression? Temporal Effects in a Community Sample of Marijuana-Using Couples.

OBJECTIVE: Although patterns of marijuana use are positively associated with intimate partner aggression, there is little evidence that episodes of marijuana use contribute to the occurrence of episodes of relationship conflict and aggression. The present ecological momentary assessment study considered the temporal relationship between marijuana use episodes and the occurrence of conflict, verbal aggression, and physical aggression between intimate partners in the next 2 hours. METHOD: A sample of 183 cohabiting marijuana-using couples (ages 18-30) were recruited from the community. For 30 consecutive days, each partner independently reported episodes of marijuana use and partner conflict, including verbal and physical aggression perpetration and victimization within conflicts. Temporal associations between each partner's marijuana use and subsequent conflict and aggression were examined using the Actor-Partner Interdependence Model. Analyses accounted for between-person effects of marijuana use frequency and total conflicts. RESULTS: We observed temporal effects of actor (but not partner) marijuana use on men's and women's reports of conflict and verbal aggression perpetration and victimization within 2 hours of use. Marijuana use episodes did not alter the likelihood of physical aggression in the next 2 hours. Partner concordance in marijuana use had no effect on verbal or physical aggression or victimization. The positive temporal effects of marijuana on conflict and verbal aggression remained significant after accounting for the effect of drinking episodes. CONCLUSIONS: Within generally concordant, marijuana-using young couples, marijuana use episodes contribute to the occurrence of relationship conflict and verbal aggression.

Difficulties in emotion regulation in treatment-seeking alcoholics with and without co-occurring mood and anxiety disorders.

Emotion regulation difficulties (ERD) are known to underlie mental health conditions including anxiety and depressive disorders and alcohol use disorder (AUD). Although AUD, mood, and anxiety disorders commonly co-occur, no study has examined the association between these disorders and ERD among AUD outpatients. In the current study, emotion regulation (ER) scores of AUD individuals with no co-occurring mental health condition were compared to the ER scores of individuals who met diagnostic criteria for co-occurring mood and/or anxiety disorders. Treatment-seeking AUD individuals (N=77) completed measures of emotion regulation, alcohol use and psychological functioning prior to beginning a 12-week outpatient cognitive-behaviorally oriented alcohol treatment program. Individuals were classified as having no co-occurring mood or anxiety disorder (AUD-0, n=24), one co-occurring disorder (AUD-1, n=34), or two or more co-occurring disorders (AUD-2, n=19). Between-group differences in emotion regulation, quantity/frequency of alcohol consumption, positive and negative affect, affective drinking situations, negative mood regulation expectancies, distress tolerance, alexithymia, trait mindfulness, and psychological symptom severity were examined. Compared with the AUD-0 group, the AUD-2 group reported significantly greater ERD, psychiatric distress and alcohol consumption, more frequent drinking in response to negative affect situations, greater interference from negative emotions, and less use of mindfulness skills. The AUD-1 group differed from AUD-0 group only on the DERS lack of emotional awareness (Aware) subscale. Emotion regulation scores in the AUD-0 group were comparable to those previously reported for general community samples, whereas levels of ERD in the AUD-1 and AUD-2 were similar to those found in other clinical samples. Implications for the inclusion of ER interventions among AUD patients who might most benefit from such an intervention are discussed.

Prospective Pilot Study of the Mastering Each New Direction Psychosocial Family Systems Program for Pediatric Chronic Illness.

Psychosocial interventions for pediatric chronic illness (CI) have been shown to support health management. Interventions that include a family systems approach offer potentially stronger and more sustainable improvements. This study explores the biopsychosocial benefits of a novel family systems psychosocial intervention (MEND: Mastering Each New Direction). Forty-five families participated in a 21-session intensive outpatient family systems-based program for pediatric CI. Within this single arm design, families were measured on five domains of Health-Related Quality of Life (HRQL) self-report measures; Stress, Cognitive Functioning, Mental Health, Child HRQL, Family Functioning. Both survey and biological measures (stress: catecholamine) were used in the study. Results from multivariate general linear models showed positive pre-, post-, and 3-month posteffects in all five domains. The program effects ranged from small to moderate (η2  = .07-.64). The largest program effects were seen in the domains of cognitive functioning (η2  = .64) and stress (η2  = .27). Also, between disease groups, differences are noted and future implications for research and clinical practice are discussed. Conclusions suggest that the MEND program may be useful in helping families manage pediatric chronic illnesses. Study results also add to the growing body of literature suggesting that psychosocial interventions for pediatric chronic illness benefit from a family systems level of intervention.

Interpersonal problems and negative affect in Borderline Personality and Depressive Disorders in daily life.

Theories of Borderline Personality Disorder (BPD) suggest that interpersonal problems in BPD act as triggers for negative affect and, at the same time, are a possible result of affective dysregulation. Therefore, we assessed the relations between momentary negative affect (hostility, sadness, fear) and interpersonal problems (rejection, disagreement) in a sample of 80 BPD and 51 depressed outpatients at 6 time-points over 28 days. Data were analyzed using multivariate multi-level modeling to separate momentary-, day-, and person-level effects. Results revealed a mutually reinforcing relationship between disagreement and hostility, rejection and hostility, and between rejection and sadness in both groups, at the momentary and day level. The mutual reinforcement between hostility and rejection/disagreement was significantly stronger in the BPD group. Moreover, the link between rejection and sadness was present at all three levels of analysis for the BPD group, while it was localized to the momentary level in the depressed group.

A Cost-Benefit Analysis of a Family Systems Intervention for Managing Pediatric Chronic Illness.

Despite recent increases of psychosocial programs for pediatric chronic illness, few studies have explored their economic benefits. This study investigated the costs-benefits of a family systems-based, psychosocial intervention for pediatric chronic illness (MEND: Mastering Each New Direction). A quasi-prospective study compared the 12-month pre-post direct and indirect costs of 20 families. The total cost for program was estimated to $5,320. Families incurred $15,249 less in direct and $15,627 less in indirect costs after MEND. On average, medical expenses reduced by 86% in direct and indirect costs, for a cost-benefit ratio of 0.17. Therefore, for every dollar spent on the program, families and their third payers saved approximately $5.74. Implications for healthcare policy and reimbursements are discussed.

Cannabis and alcohol use, affect and impulsivity in psychiatric out-patients' daily lives.

BACKGROUND AND AIMS: Cannabis and alcohol are the most commonly used (il)licit drugs world-wide. We compared the effects of cannabis and alcohol use on within-person changes in impulsivity, hostility and positive affect at the momentary and daily levels, as they occurred in daily life. DESIGN: Observational study involving ecological momentary assessments collected via electronic diaries six random times a day for 28 consecutive days. SETTING: Out-patients' everyday life contexts in Columbia, MO, USA. PARTICIPANTS: Ninety-three adult psychiatric out-patients (85% female; mean = 30.9 years old) with borderline personality or depressive disorders, who reported using only cannabis (n = 3), only alcohol (n = 58) or both (n = 32) at least once during the study period. MEASUREMENTS: Real-time, standard self-report measures of impulsivity, hostility and positive affect, as impacted by momentary reports of cannabis and alcohol use. FINDINGS: Cannabis use was associated with elevated feelings of impulsivity at the day level [b = 0.83, 95% confidence interval (CI) = 0.17-1.49] and increased hostility at the momentary (b = 0.07, 95% CI = 0.01-0.12) and person (b = 0.81, 95% CI = 0.15-1.47) level. Alcohol use was associated with elevated feelings of impulsivity at the momentary (b = 0.42, 95% CI = 0.13-0.71) and day levels (b = 0.82, 95% CI = 0.22-1.41) and increased positive affect at the momentary (b = 0.12, 95% CI = 0.06-0.18) and day (b = 0.33, 95% CI = 0.16-0.49) levels. CONCLUSIONS: Cannabis and alcohol use are associated with increases in impulsivity (both), hostility (cannabis) and positive affect (alcohol) in daily life, and these effects are part of separate processes that operate on different time-scales (i.e. momentary versus daily).

A systematic review of the PTSD Checklist's diagnostic accuracy studies using QUADAS.

Despite the popularity of the PTSD Checklist (PCL) as a clinical screening test, there has been no comprehensive quality review of studies evaluating its diagnostic accuracy. A systematic quality assessment of 22 diagnostic accuracy studies of the English-language PCL using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment tool was conducted to examine (a) the quality of diagnostic accuracy studies of the PCL, and (b) whether quality has improved since the 2003 STAndards for the Reporting of Diagnostic accuracy studies (STARD) initiative regarding reporting guidelines for diagnostic accuracy studies. Three raters independently applied the QUADAS tool to each study, and a consensus among the 4 authors is reported. Findings indicated that although studies generally met standards in several quality areas, there is still room for improvement. Areas for improvement include establishing representativeness, adequately describing clinical and demographic characteristics of the sample, and presenting better descriptions of important aspects of test and reference standard execution. Only 2 studies met each of the 14 quality criteria. In addition, study quality has not appreciably improved since the publication of the STARD Statement in 2003. Recommendations for the improvement of diagnostic accuracy studies of the PCL are discussed.