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Objective Various factors contribute to the effective implementation of evidence-based treatments (EBTs). In this study, cognitive processing therapy (CPT) was administered in a Veterans Affairs (VA) posttraumatic stress disorder (PTSD) specialty clinic in which training and supervision were provided following VA implementation guidelines. The aim was to (a) estimate the proportion of variability in outcome attributable to therapists and (b) identify characteristics of those therapists who produced better outcomes. Method We used an archival database of veterans (n = 192) who completed 12 sessions of CPT by therapists (n = 25) who were trained by 2 nationally recognized trainers, 1 of whom also provided weekly group supervision. Multilevel modeling was used to estimate therapist effects, with therapists treated as a random factor. The supervisor was asked to retrospectively rate each therapist in terms of perceived effectiveness based on supervision interactions. Using single case study design, the supervisor was interviewed to determine what criteria she used to rate the therapists and emerging themes were coded. Results When initial level of severity on the PTSD Checklist (PCL; McDonald & Calhoun, 2010; Weathers, Litz, Herman, Huska, & Keane, 1993) was taken into account, approximately 12% of the variability in the PCL at the end of treatment was due to therapists. The trainer, blind to the results, identified the following characteristics and actions of effective therapists: effectively addressing patient avoidance, language used in supervision, flexible interpersonal style, and ability to develop a strong therapeutic alliance. Conclusions This study adds to the growing body of literature documenting the importance of the individual therapist as an important factor in the change process.

ObjectiveTo describe the frequency of self-weighing and reactions to prescribed weekly weighing among individuals with eating disorder (ED) diagnoses, and to compare individuals weighing more or less frequently on mass index (BMI) and the Eating Disorder Examination (EDE) subscales.MethodBaseline EDE and demographics from five studies (N = 758).ResultsSelf-weighing was most frequent among individuals with anorexia nervosa (AN), followed by those with bulimia nervosa (BN) and binge eating disorder (BED). On average, participants reacted moderately negative to prescribed weekly weighing. No relationship between weighing frequency and BMI was evident in any sample. There was indication of greater pathology (i.e., restraint, shape concern, weight concern, global) in AN with more frequent weighing. In BN, mixed evidence emerged to support a relationship between more frequent weighing and higher shape concern, weight concern, and global score. In BED, higher restraint was found in those who weighed versus those who did not.DiscussionWeighing frequency in each eating disorder (ED) sample was to some extent associated with greater ED severity, but not BMI. Future research should examine relationships between self-weighing, reactions to changing weighing frequency, and ED symptomatology in both ED and non-ED groups to understand the impact of self-weighing in heterogeneous populations. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:817-821).

This study examined self-discrepancy, a construct of theoretical relevance to eating disorder (ED) psychopathology, across different types of EDs. Individuals with anorexia nervosa (AN; n = 112), bulimia nervosa (BN; n = 72), and binge eating disorder (BED; n = 199) completed semi-structured interviews assessing specific types of self-discrepancies. Results revealed that actual:ideal (A:I) discrepancy was positively associated with AN, actual:ought (A:O) discrepancy was positively associated with BN and BED, and self-discrepancies did not differentiate BN from BED. Across diagnoses, A:O discrepancy was positively associated with severity of purging, binge eating, and global ED psychopathology. Further, there were significant interactions between diagnosis and A:O discrepancy for global ED psychopathology and between diagnosis and A:I discrepancy for binge eating and driven exercise. These results support the importance of self-discrepancy as a potential causal and maintenance variable in EDs that differentiates among different types of EDs and symptom severity. Copyright © 2016 John WileySons, Ltd and Eating Disorders Association.

Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived. Here we designed a hybrid adeno-associated virus and phage (AAVP) vector displaying biologically active octreotide on the viral surface for ligand-directed delivery, cell internalization, and transduction of an apoptosis-promoting tumor necrosis factor (TNF) transgene specifically to NETs. These functional attributes of AAVP-TNF particles displaying the octreotide peptide motif (termed Oct-AAVP-TNF) were confirmed in vitro, in SSTR type 2-expressing NET cells, and in vivo using cohorts of pancreatic NET-bearing Men1 tumor-suppressor gene KO mice, a transgenic model of functioning (i.e., insulin-secreting) tumors that genetically and clinically recapitulates the human disease. Finally, preclinical imaging and therapeutic experiments with pancreatic NET-bearing mice demonstrated that Oct-AAVP-TNF lowered tumor metabolism and insulin secretion, reduced tumor size, and improved mouse survival. Taken together, these proof-of-concept results establish Oct-AAVP-TNF as a strong therapeutic candidate for patients with NETs of the pancreas. More broadly, the demonstration that a known, short, biologically active motif can direct tumor targeting and receptor-mediated internalization of AAVP particles may streamline the potential utility of myriad other short peptide motifs and provide a blueprint for therapeutic applications in a variety of cancers and perhaps many nonmalignant diseases as well.

OBJECTIVE This study examined predictors and moderators of outcome in 2 treatments for bulimia nervosa (BN). METHOD Eighty adults with BN symptoms at 1 of 2 sites were randomized to 21 sessions of integrative cognitive-affective therapy for BN (ICAT-BN) or enhanced cognitive behavior therapy (CBT-E). Generalized linear models examined predictors and moderators of improvements in bulimic behavior and eating disorder psychopathology at end of treatment (EOT) and 4-month follow-up (FU). RESULTS At EOT, individuals with higher dietary restraint had greater reductions in bulimic behavior. At FU, individuals with higher weight and shape concern had greater reductions in bulimic behavior, whereas those with greater baseline depression had less improvement in eating disorder psychopathology. Individuals higher in stimulus seeking had greater reductions in bulimic behavior and eating disorder psychopathology at follow up in ICAT-BN than in CBT-E, whereas individuals lower in stimulus seeking had greater reductions in bulimic behavior in CBT-E than in ICAT-BN. Finally, individuals with higher affective lability had greater reductions in eating disorder psychopathology in ICAT-BN than in CBT-E, whereas improvements were comparable across treatments for individuals with lower affective lability. CONCLUSIONS This study identified 3 nonspecific predictors of outcome (i.e., dietary restraint, weight and shape concern, and depression) and 2 moderators (i.e., affective lability and stimulus seeking). All moderator effects emerged at FU rather than at EOT, suggesting that the moderating effects of treatment were not immediately apparent. These results suggest that individuals with higher affective lability and stimulus seeking may benefit more from treatment with a greater focus on affective states and self-regulation.

Objective: Two studies sought to examine predictions of the Integrative Cognitive-Affective Therapy (ICAT) model, which views bulimic symptoms in terms of inter-relations between self-concept discrepancies, negative affect, and selfdirected coping styles. The present results examine assessment-related predictions of this model. Method: Individuals with bulimic symptoms were compared to noneating disorder control participants in two studies involving central constructs of the ICAT model. Results: In both studies, bulimic individuals displayed higher levels of selfdiscrepancy and negative self-directed styles, supporting predictions of the model. Also predicted by the model, negative mood states mediated relations between bulimic status and negative selfdirected coping styles in Study 2. Conclusion: Assessment-related predictions of the ICAT model of bulimic symptoms were supported in two studies. These initial results support further tests of the model in longitudinal designs, contrasts of different clinical populations, and treatment-evaluation studies. V

The inclusion of different carrier materials in a dry powder inhaler (DPI) system can alter formulation performance, which might be attributable to variation in the adhesion between drug and carrier particles. The aim of this study was, therefore, to further examine the relationship between drug-carrier adhesion and performance, by comparing data relating to many different drug-carrier combinations. Four drugs and four carriers were employed, giving a total of 16 combinations. The relative magnitude of the drug-carrier adhesion for each combination was quantified using the cohesion-adhesion balance (CAB) approach to colloidal probe atomic force microscopy. The in vitro inhalation performance of the 16 formulations (1.5% w/w drug) was investigated and found to vary significantly. Plots of fine particle dose against drug-carrier CAB ratio revealed that performance was optimised when the drug-carrier CAB ratio was slightly cohesive. This trend was found to fit with those from similar previous studies, although due to the smaller number of formulations investigated previously, the full extent of this relationship had not been revealed. It was concluded, therefore, that when developing a carrier-based DPI, the selection of a drug-carrier combination with a slightly cohesive CAB ratio might result in optimal performance.

The purpose of this investigation was to examine the indirect effects of Integrative Cognitive-Affective Therapy (ICAT-BN) and Cognitive-Behavioral Therapy-Enhanced (CBT-E) on bulimia nervosa (BN) treatment outcome through three hypothesized maintenance variables: emotion regulation, self-directed behavior, and self-discrepancy.Eighty adults with BN were randomized to 21 sessions of ICAT-BN or CBT-E. A regression-based bootstrapping approach was used to test the indirect effects of treatment on outcome at end of treatment through emotion regulation and self-directed behavior measured at mid-treatment, as well as the indirect effects of treatment at follow-up through emotion regulation, self-directed behavior, and self-discrepancy measured at end of treatment.No significant differences in outcome between treatment conditions were observed, and no significant direct or indirect effects were found. Examination of the individual paths within the indirect effects models revealed comparable treatment effects. Across treatments, improvements in emotion regulation and self-directed behavior between baseline and mid-treatment predicted improvements in global eating disorder scores but not binge eating and purging frequency at end of treatment. Baseline to end of treatment improvements in emotion regulation and self-directed behavior also predicted improvements in global eating disorder scores at follow-up. Baseline to end of treatment improvements in emotion regulation predicted improvements in binge eating and baseline to end of treatment increases in positive self-directed behavior predicted improvements in purging at follow-up.These findings suggest that emotion regulation and self-directed behavior are important treatment targets and that ICAT-BN and CBT-E are comparable in modifying these psychological processes among individuals with BN.

Introduction In an effort to improve access to and utilization of health care, the Veterans Health Administration (VHA) continues to investigate the effectiveness of video-teleconferencing (VTC) technologies for service delivery. While previous research focused on the efficacy of VTC treatment for post-traumatic stress disorder (PTSD) in Vietnam era veterans, few studies have evaluated the efficacy of this modality and treatment for the Iraq/Afghanistan era veterans. The aim of this randomized clinical trial was to evaluate equivalence between in person and VTC psychotherapy for PTSD in this newer cohort. Methods Veterans of the Iraq/Afghanistan conflict from two VHA hospitals in the United States were recruited and randomized to receive cognitive processing therapy (CPT) for PTSD either in person (IP) or over VTC. Clinician-administered and self-report measures were collected before, during, and after treatment. Results A trend was observed which suggested that CPT over VTC may be equivalent to the treatment delivered in person, as suggested by previous studies. Regardless of treatment, veterans who received the intervention in both conditions reported significant decreases on post-treatment measures. Discussion This study highlighted research and clinical challenges in providing services to the newest veteran generation in general as well as unique challenges with VTC. One complicating factor to the statistical power of this study was a treatment dropout rate twice the original estimate. Factors that could have influenced this high dropout rate are explored.

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial–melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell–cell interactions at the lymphatic–tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

In a prior study (KoldenKlein, 1996), the authors found that the relationships between global personality pathology and early psychotherapy change processes (as defined by the Generic Model of Psychotherapy) were moderated by the extent of the patient's acute symptomatic and interpersonal distress. In the current study, the authors reanalyzed the same data to examine similarities and differences between personality disorder Clusters B (dramatic, emotional, or erratic) and C (anxious or fearful) in therapy process. In general, we found that more distressed patients reported greater defensiveness. There were no significant interactions between symptomatic distress and personality pathology in the prediction of any of the process variables. However, interpersonal distress moderated relationships between Clusters B and C and some therapy processes. Patients high in Cluster B felt more open and involved in the session when they were less distressed by their interpersonal problems at the start of therapy. In contrast, openness and insight were impeded among patients high in Cluster C when they were less distressed interpersonally. Therapists generally used more direct interventions and exploration of past experiences when working with patients higher in Cluster C pathology. However, therapists used direct interventions more specifically when patients with more severe Cluster B pathology were also higher in interpersonal distress. The discussion considers implications for the facilitation of productive early therapy process in patients suffering from Cluster B or C personality pathology.

The authors examined the link between interpretive techniques, the therapeutic relationship, and outcome in psychodynamic psychotherapy. Two independent teams of judges each coded one early session from patients diagnosed with avoidant personality disorder. Results revealed (a) an inverse association between concentration of interpretation and favorable patient outcome; (b) that small amounts of disaffiliative patient‐ therapist transactions before, during, and after interpretations were reliably or meaningfully associated with negative patient change; and (c) concentration of interpretation was positively associated with disaffiliative therapy process before and during interpretation and negatively associated with affiliative patient responses to interpretation. The results suggest that therapists who persisted with interpretations had more hostile interactions with patients and had patients who reacted with less warmth than therapists who used interpretations more judiciously.

The Wisconsin Personality Disorders Inventory (WISPI-IV; Klein & Benjamin, 1996) is the latest version of a self-report measure of DSM-IV personality disorders (PDs) derived from an interpersonal perspective. When categorical diagnoses derived from the WISPI-IV were compared with independent SCID-II diagnoses, the majority of the kappas were poor (>.40). However, all but one of the effect sizes for the differences in WISPI-IV means between groups with and without SCID-II diagnoses were large (>.80). When SCID-II and WISPI-IV dimensional scores were considered, the average r between profiles was .61 (median = .58) and correlations between corresponding PD scales (mean diagonal r = .48; mean off-diagonal r = .18) indicated good convergent and discriminant validity for five of the WISPI-IV scales. These results add to the cumulating evidence suggesting greater reliability and validity of dimensional over categorical scores for PDs. Researchers and clinicians interested in having an efficient method of assessing PDs may consider using a dimensional approach such as the WISPI-IV as an alternative to diagnostic interview.

e16578 Background: Approved by the FDA as a diagnostic test, the long non-coding RNA PCA3 is the most specific human prostate cancer biomarker identified to date. The biological function of PCA3, which involves downregulating the tumor suppressor gene PRUNE2, has important therapeutic implications. Here we investigated RNA expression levels of these genes to better understand the dynamics of this regulatory process during cancer progression and its relevance for tumor aggressiveness. Methods: We downloaded clinical data, as well as PCA3 and PRUNE2 gene expression values (log2 RSEM), from 497 TCGA prostate cancer patients (totaling 550 samples) and their matched normal tissues using the Xena Browser. Expression values for both genes, and their ratios, were evaluated in terms of tumor vs non-tumor tissue, biochemical recurrence, pathologic T stage, Gleason scores and age at diagnosis. All p-values were obtained by the Wilcoxon rank Sum (2 groups) or the Kruskal-Wallis Test (3+ groups). Results: Using 52 malignant/non-malignant tissue pairs from our cohort, we confirmed previous findings that showed simultaneous PCA3 upregulation and PRUNE2 reduction in malignant samples when compared to non-malignant ( p7) and in younger subjects (

Behavioral intervention studies in patients with an implantable cardioverter-defibrillator (ICD) show promise in improving psychosocial outcomes but inconclusive effects on cardiovascular outcome. We assessed the effects of cognitive behavioral stress management (CBSM) on mood state and potentially arrhythmogenic cardiovascular responses to mental stress in ICD patients, in support of further larger scale arrhythmia trials.A total of 103 ICD recipients were randomly assigned to 10-week programs of CBSM or "Patient Education" (ED). Of these, 83 patients continued to either CBSM (n = 44) or ED (n = 39) intervention. Study end points were mood change, heart rate variability (HRV), double product elevation (DP = heart rate × systolic blood pressure) by math and anger-recall stress, and arrhythmia up to 6 months follow-up.Adjusting for multiple testing, CBSM was associated with moderate effect size reductions in tension/anxiety (P = 0.010), anger/hostility (P = 0.020), perceived stress (P = 0.037), and total mood disturbance (P = 0.025), greatest immediately following intervention (P0.05), and partially attributable to increased negative mood following ED (P0.01). No significant intervention effects on high frequency or low frequency spectral power of HRV, DP responses, or cardiac arrhythmias were demonstrated.CBSM intervention in ICD recipients resulted in reduced anxiety, anger, and perceived stress, not sustained at 6 months follow-up, and without conclusive effect on cardiac autonomic or hemodynamic responses to mental stress, or arrhythmia. Findings support conduct of larger behavioral intervention arrhythmia trial, with consideration of reinforcement training and targeting of subgroup responders to therapy.

Personality disorders (PD) are a prevalent class of mental disorders that interfere with functioning and cause subjective distress while increasing the intensity and duration of Axis I clinical syndromes, and therefore assessing PD is important even when PDs are not the focus of treatment. The purpose of these studies was to develop and test a new Spanish version of a self-report measure of PD, the Wisconsin Personality Inventory-IV (WISPI-IV) that would be psychometrically equivalent to the English version while also maintaining the same interpersonal content, which is based on Benjamin's analysis of the PD criteria using her Structural Analysis of Social Behavior (SASB) model (1974). Study 1 participants completed the WISPI-IV twice over a two-week interval. For Study 2, participants from two sites in Spain and one site in Argentina completed Spanish versions of the WISPI-IV and other personality measures. SASB-analysis of the translated items showed high correspondence between the interpersonal content of the English version and the Spanish version demonstrating theoretical validation in relation to other PD measures. The Spanish WISPI-IV showed satisfactory reliability based on test-retest correlations and alphas for internal consistency. Study 2 showed the Spanish WISPI-IV had good convergent validity with the Spanish versions of the IIP and SCID-II and performed similarly to the English versions of these measures. Our goal in translating the WISPI-IV was to extend this measure to Spanish-speakers in language that would be understood by different Hispanic sub-groups, however research team members and subjects had a variety of suggestions for changes in item wording. This reflects the difficulty with creating a "neutral" Spanish version of any assessment given regional differences.

Reports an error in "Therapist Interpretation, Patient-Therapist Interpersonal Process, and Outcome in Psychodynamic Psychotherapy for Avoidant Personality Disorder" by Alexander J. Schut, Louis G. Castonguay, Kelly M. Flanagan, Alissa S. Yamasaki, Jacques P. Barber, Jamie D. Bedics and Tracey L. Smith (Psychotherapy: Theory, Research, Practice, Training, 2005 Win, Vol 42(4), 494-511). The correct legend for Figure 1 on page 500 should read as follows: Figure 1. The SASB circumplex model, cluster version, interpersonal surfaces. Adapted from Benjamin (1993), Interpersonal diagnosis and treatment of personality disorders. New York: Guilford Press, copyright Guilford Press, and from: Benjamin (1987), Use of the SASB dimensional model to develop treatment plans for personality disorders, I: Narcissism. Journal of Personality Disorders, 1, 43-70, copyright Guilford Press. (The following abstract of the original article appeared in record 2006-03309-008.) The authors examined the link between interpretive techniques, the therapeutic relationship, and outcome in psychodynamic psychotherapy. Two independent teams of judges each coded one early session from patients diagnosed with avoidant personality disorder. Results revealed (a) an inverse association between concentration of interpretation and favorable patient outcome; (b) that small amounts of disaffiliative patient-therapist transactions before, during, and after interpretations were reliably or meaningfully associated with negative patient change; and (c) concentration of interpretation was positively associated with disaffiliative therapy process before and during interpretation and negatively associated with affiliative patient responses to interpretation. The results suggest that therapists who persisted with interpretations had more hostile interactions with patients and had patients who reacted with less warmth than therapists who used interpretations more judiciously. (PsycINFO Database Record (c) 2010 APA, all rights reserved).