Deriving the Transdiagnostic Scales From the Personality Assessment Inventory and SPECTRA: Indices of Psychopathology: A Demonstration.

Transdiagnostic models of psychopathology address many of the shortcomings common to categorical diagnostic systems. These empirically derived models conceptualize psychopathology as a few broad interrelated and hierarchically arranged dimensions, with an overarching general psychopathology dimension, the p-factor, at the apex. While transdiagnostic models are gaining prominence in mental health research, the lack of available tools has limited their clinical translation. The present study explored the potential of creating transdiagnostic scales from the joint factor structure of the Personality Assessment Inventory, Alternative Model of Personality Disorder trait scales (AMPD), and the clinical scales of the SPECTRA: Indices of Psychopathology (SPECTRA). Exploratory factor analysis in a clinical sample (n = 212) identified five factors corresponding to the Negative Affect/Internalizing, Detachment, Antagonism/Externalizing, Disinhibition/Externalizing, and Thought Disorder transdiagnostic dimensions. Goldberg's "Bass-Ackward" method supported a hierarchical structure. Five composite transdiagnostic scales were created by summing each factor's highest loading PAI and SPECTRA scales. A global psychopathology scale was created by summing the five composite scales. All the composite scales demonstrated adequate internal consistency. Correlations between the composite scales and the NEO Five-Factor Inventory-3 provide initial validity evidence for four composite and global scales. The composite thought disorder scale had no conceptually corresponding NEO domain. Clinical implications and study limitations are discussed.

Using the Personality Assessment Inventory to Assess the Alternative Model for Personality Disorders: Criterion Validity in a Clinical Sample.

The Personality Assessment Inventory (PAI) is a broadband measure of psychopathology that is widely used in applied settings. Researchers developed regression-based estimates that use the PAI to measure constructs of the Alternative Model for Personality Disorders (AMPD) - a hybrid dimensional and categorical approach to conceptualizing personality disorders. Although prior work has linked these estimates to formal measures of the AMPD, there is little work investigating the clinical correlates of this scoring approach of the PAI. The current study examines associations between these PAI-based AMPD estimates and life data in a large, archival dataset of psychiatric outpatients and inpatients. We found general support for the criterion validity of AMPD estimate scores, such that a theoretically consistent pattern of associations emerged with indicators such as prior academic achievement, antisocial behavior, psychiatric history, and substance abuse. These results provide preliminary support to this scoring approach for use in clinical samples.

The Impact of Different Thematic Apperception Test Administration Methods on Narrative Length and Story Richness as Measured by the Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G).

The Thematic Apperception Test (TAT) is the second most commonly used performance-based task in clinical practice. However, traditional TAT administration is time-consuming and raises accessibility issues. This study examines the effect of administration modifications (i.e., examiner handwriting versus typing, examiner recording versus participant recording, and re-prompting versus no re-prompting) on narrative length and richness as measured by the Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G). A four-card TAT protocol was administered to 150 college students under one of five conditions. The resulting narratives were scored by two trained raters using the SCORS-G. MANOVA procedures showed (a) no significant differences between examiner handwriting versus typing; (b) the shortest, blandest narratives were produced when the examiner recorded the narratives without re-prompting; and (c) the longest, richest narratives were produced when the participant typed the narratives with re-prompts on the computer screen. Clinical and research implications and future directions will be discussed.

RNA-Based Homologous Recombination Deficiency Signature Detects Homologous Recombination Deficiency-RNA+ Patients With and Without Homologous Recombination Repair Gene Pathogenic Alterations in Men With Prostate Cancer.

PURPOSE: Homologous recombination deficiency (HRD) is a well-described phenotype of some prostate cancers; however, current biomarkers for HRD are imperfect and rely on detection of single gene alterations in the homologous recombination repair (HRR) pathway, which may not capture the complexity of HRD biology. RNA signature-based methods of HRD identification present a potentially dynamic assessment of the HRD phenotype; however, its relationship with HRR gene alterations is not well characterized in prostate cancer. METHODS: A HRD assay on the basis of an RNA signature associated with biallelic BRCA1/2 loss was applied to a retrospective cohort study of 985 men with prostate cancer analyzed on the Tempus xT platform. HRD status was defined by a binary threshold on a continuous scale. RESULTS: In this cohort, of the 126 (13%) patients found to be HRD+ by RNA signature (HRD-RNA+), 100 (79%) had no coexisting HRR gene alteration. Among samples with biallelic BRCA1/2 loss, 78% (7/9) were classified as HRD-RNA+, while 8% (2/25) of samples with BRCA1/2 monoallelic loss were HRD-RNA+. Biallelic and monoallelic ATM loss exhibited HRD-RNA+ at a lower prevalence: 6.7% (1/15) and 7.1% (1/14), respectively, compared with HRD-RNA+ prevalence among samples without any HRR gene loss (13%; 100/782). HRD-RNA+ was associated with a significantly higher prevalence of TP53 and AR gene alterations relative to HRD-RNA- after correction for multiple comparisons, 59% versus 39% (q = 0.003) and 23% versus 12% (q = 0.024), respectively. CONCLUSION: Use of an RNA-based HRD signature significantly expands the fraction of patients with prostate cancer who may derive benefit from poly (ADP-ribose) polymerase inhibitors (PARPis) compared with using HRR gene mutations alone. Further studies are needed to evaluate functional HRD significance and inform future usage as a predictive biomarker for PARPi selection.

Early childhood educator outcomes from online professional development for physical literacy: A randomised controlled trial.

INTRODUCTION: Early childhood is recognised as a critical window of opportunity for physical literacy development, however early childhood educators typically lack the training required to effectively provide appropriate physical literacy opportunities for children. We examined the effects of an online physical literacy professional development program-relative to continuing with 'standard' practice-on early childhood educators' physical literacy knowledge and application. METHODS: We conducted a parallel two-arm randomised controlled trial, in which 88 early childhood educators were randomly assigned to an online professional development program designed to support educators' physical literacy instructional skills (intervention arm; n = 37), or a 'standard practice' control condition (n = 51). Data were collected prior to and after the four-week intervention period. We measured educators' physical literacy knowledge and application (our primary outcome) through independent coding of open-ended survey responses, and educators' self-reported perceptions of values, confidence, behaviours, and barriers (secondary outcomes). Between-group differences were assessed through analysis of covariance. RESULTS: One intervention arm participant withdrew from the study, resulting in 87 participants included in analysis. Educators in the intervention arm scored significantly higher on post-intervention physical literacy knowledge (d = 0.62) and application (d = 0.33) than those in the control arm. Educators in the intervention arm also scored significantly higher than controls on confidence in teaching physical activity (d = 0.42) and significantly lower than controls on perceived personal barriers to physical activity (d = 0.53). Thirteen participants in the intervention arm (36%) did not begin the online professional development program. CONCLUSION: Improvements in physical literacy instructional outcomes indicate the potential for further investigation into broader implementation of online professional development programs of this nature in the future.

Psychology Internship Training Amidst COVID-19: Balancing Training Opportunities, Patient Care, and Risk of Exposure.

The emergence of the 2019 novel coronavirus (COVID-19) has dramatically altered how psychologists deliver its training. At least for the time being, virtual care has become the primary method for delivering mental health services. This has allowed patients and clinicians to continue to access and provide services in a way that would have been impossible years ago. Not only has this shift impacted patients, but it has also impacted supervision and training. The impact has been especially profound on inpatient units where the psychiatric and medical acuity is high of patients and the therapeutic milieu is an important aspect of treatment. The purpose of this paper is to review the impact of COVID-19 on pre-doctoral psychology interns during their rotation on an inpatient psychiatry unit at the start of the pandemic (January to June of 2020) and use these experiences to onboard the next class of interns in the new academic year (July 2020 to June 2021) using a hybrid model of in-person and virtual training experiences. At the end of 2020/2021 rotation, we voluntarily asked interns to complete a questionnaire that was developed based on the qualitative experiences of the previous class to assess the effectiveness of this hybrid model. We also surveyed multi-disciplinary staff members who were essential personnel and required to work in person during this time about their experiences of safety and support. With this information, we explore and offer guidance to other inpatient training sites who are likely to encounter similar challenges during this time. In particular, we discuss the integration of virtual technology into this training experience, as well as the restructuring of clinical and supervisory experiences. We highlighted several short-term strategies that we have flexibly adapted to our inpatient unit. The lessons learned herein seek to guide supervisors and trainees alike in adapting their psychology training programs to meet the evolving demands of COVID-19.

Comparison of the tumor immune microenvironment and checkpoint blockade biomarkers between stage III and IV non-small cell lung cancer.

BACKGROUND: Adjuvant immune checkpoint blockade (ICB) following chemoradiotherapy and adding ICB to chemotherapy have been key advances for stages III-IV non-small cell lung cancer (NSCLC) treatment. However, known biomarkers like PD-L1 are not consistently indicative of ICB response. Other markers within the tumor immune microenvironment (TIME) may better reflect ICB response and/or resistance mechanisms, but an understanding of how TIMEs differ between stage III and IV NSCLC has not been explored. METHODS: Real-world data from unresectable, stage III-IV, non-squamous, pretreatment NSCLCs (stage III n = 106, stage IV n = 285) were retrospectively analyzed. PD-L1 immunohistochemistry (IHC) was compared to CD274 gene expression. Then, differential gene expression levels, pathway enrichment, and immune infiltrate between stages were calculated from whole-transcriptome RNA-seq. Analyses were stratified by EGFR status. RESULTS: PD-L1 IHC and CD274 expression in tumor cells were highly correlated (n = 295, P < 2.2e-16, ⍴ = 0.74). CTLA4 expression was significantly increased in stage III tumors (P = 1.32e-04), while no differences were observed for other ICB-related genes. Metabolic pathway activity was significantly enriched in stage IV tumors (P = 0.004), whereas several immune-related KEGG pathways were enriched in stage III. Stage IV tumors had significantly increased macrophage infiltration (P = 0.0214), and stage III tumors had a significantly higher proportion of CD4 + T cells (P = 0.017). CD4 + T cells were also relatively more abundant in EGFR-mutant tumors vs. wild-type (P = 0.0081). CONCLUSION: Directly comparing the TIMEs of stage III and IV NSCLC, these results carry implications for further studies of ICB response in non-resectable stage III NSCLC and guide further research of prognostic biomarkers and therapeutic targets.

[Positive experiences of specialist assistants and physicians with respect to the delegation research project StaerkeR : Evaluation of the training and experiences within the framework of this project]. / Positive Erfahrungen von Fachassistent:innen und Ärzt:innen hinsichtlich des Delegations-Forschungsprojekts StärkeR : Evaluation der Schulung und Erfahrungen im Rahmen dieses Projekts.

INTRODUCTION: The delegation of medical services to rheumatology assistants (RFA) has proven to be safe and effective in the evaluation of the research project "StaerkeR". Afterwards, the experiences of the participating RFAs and rheumatologists with delegation were surveyed and discussed within the framework of an opinion research project. METHODS: At the end of the project, the participating RFAs and rheumatologists were surveyed via an online questionnaire (quantitative analysis) (21 questions for physicians and 44 questions for RFAs). In addition, focus group meetings were held for the RFAs, which were led by a moderator and a secretary. The results of the focus group sessions (qualitative analyses) were analyzed according to the structured method of Kuckartz. RESULTS: All 31 RFAs and 25 rheumatologists involved in the project participated in the online surveys and 9 RFAs took part in the 2 focus groups. In the online surveys, both the RFAs and the rheumatologists gave predominantly good to very good ratings with respect to RFA training, the implementation of delegation in the practices and outpatient clinics, the role of the RFAs and the overall evaluation of the delegation concept. In the focus group discussions, many possible limitations regarding acceptance and implementation of the delegation concept were mentioned. CONCLUSION: The delegation of medical tasks to RFAs is a concept that is positively assessed and highly accepted by both sides, the rheumatologists and the RFAs. In a comparison between the individual practices and hospital outpatient departments, there is still a clear heterogeneity with respect to the willingness and logistical possibilities in the implementation of the delegation concept.

Integration of tumor extrinsic and intrinsic features associates with immunotherapy response in non-small cell lung cancer.

The efficacy of immune checkpoint blockade (ICB) varies greatly among metastatic non-small cell lung cancer (NSCLC) patients. Loss of heterozygosity at the HLA-I locus (HLA-LOH) has been identified as an important immune escape mechanism. However, despite HLA-I disruptions in their tumor, many patients have durable ICB responses. Here we seek to identify HLA-I-independent features associated with ICB response in NSCLC. We use single-cell profiling to identify tumor-infiltrating, clonally expanded CD4+ T cells that express a canonical cytotoxic gene program and NSCLC cells with elevated HLA-II expression. We postulate cytotoxic CD4+ T cells mediate anti-tumor activity via HLA-II on tumor cells and augment HLA-I-dependent cytotoxic CD8+ T cell interactions to drive ICB response in NSCLC. We show that integrating tumor extrinsic cytotoxic gene expression with tumor mutational burden is associated with longer time to progression in a real-world cohort of 123 NSCLC patients treated with ICB regimens, including those with HLA-LOH.

Genome Sequences of Two Methicillin-Sensitive Staphylococcus aureus Healthy Skin Isolates.

The USA300 and USA600 clonal lineages are the cause of many serious Staphylococcus aureus infections. Here, we report the complete genomes of two methicillin-sensitive S. aureus strains isolated from the healthy skin of adults in Colorado, which are most phylogenetically similar to the USA300 and USA600 lineages.

An Ecological Momentary Intervention Study of Emotional Responses to Smartphone-Prompted CBT Skills Practice and the Relationship to Clinical Outcomes.

The practice of therapeutic skills outside of sessions in which they are learned is one presumed key component of cognitive behavioral therapy (CBT). Yet, our understanding of how skills practice relates to clinical outcomes remains limited. Here, we explored patients' emotional responses to CBT skills practice in a pilot study pairing smartphone-app-delivered skills reminders and guided practice (ecological momentary intervention [EMI]) using ecological momentary assessment (EMA). Participants (n = 25) were adults recently hospitalized for a suicide attempt or severe suicidal thinking. They received brief inpatient CBT (1 to 3 sessions covering core CBT skills from the Unified Protocol), followed by 1 month of EMI and EMA after discharge. On average, participants reported modest reductions in negative affect after skills use (i.e., immediate responses; median time elapsed = 4.30 minutes). Additionally, participants tended to report less negative affect when the timepoint preceding the current assessment included EMI skills practice, rather than EMA alone (i.e., delayed responses; median time elapsed between prompts = 2.17 hours). Immediate effects were unrelated to longer-term clinical outcomes, whereas greater delayed effects were associated with lower symptom severity at follow-up. Future studies should further examine how CBT skills use in daily life may alleviate symptoms.

Longitudinal stability of Social Cognition and Object Relations Scale-Global Rating Method dimensional ratings, score ranges and narrative 'blandness' in a clinical sample.

While understanding how internalized representations of others (i.e., object relations) change over the course of treatment is essential for treatment planning and evaluation of progress, few studies have examined the nature of these changes through repeated psychological assessments. In this study, we applied the SCORS-G to Thematic Apperception Test narratives for 61 adult patients with complex psychiatric problems undergoing residential treatment over an 18-month period. Over the course of treatment, patient representations of self and others became more complex, indicating improvements in mentalization. Further, an analysis of default ratings (i.e., an aspect of story 'blandness') suggested that certain shifts in SCORS-G dimensional scores over time were accounted for by greater degree of scorable content across time points, rather than changes specific to the dimensions themselves. Findings from novel exploratory analyses aimed at evaluating the test-retest reliability of both default rating proportion and several emerging alternative scoring approaches (including changes in minimum, maximum and range of scores on individual dimensions) are reported. While the magnitude of change across mean dimensional scores was found to be lower compared to those previously found in outpatient populations, our results suggest that the SCORS-G remains capable of detecting changes in mentalization capacities in individuals contending with longstanding, severe psychiatric impairment and personality-based psychopathology. Implications for treatment, assessment and future research are discussed.

Exploring the Alternative Model for Personality Disorders Using SCORS-G Ratings on Thematic Apperception Test Narratives.

The Alternative Model for Personality Disorders (AMPD) in Section III of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013) conceptualizes personality pathology as a combination of impairment (Criterion A) and traits (Criterion B). One measure used to develop Criterion A was the Social Cognition and Object Relations Scale - Global Rating Method (SCORS-G), which is a multidimensional, object-relational clinician-rated measure of personality functioning. Although there are conceptual links between the AMPD and SCORS-G dimensions, there exists no research examining the relationship. To address this, we examined associations between the SCORS-G dimensions and measures of the AMPD constructs in a large, archival dataset of outpatients and inpatients. More pathological scores on SCORS-G dimensions reflecting self- and interpersonal functioning were associated with greater pathological traits and impairment. Overall, results support further investigation into SCORS-G as a useful measure in AMPD research and assessment.

Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region.

Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.

A pan-cancer organoid platform for precision medicine.

Patient-derived tumor organoids (TOs) are emerging as high-fidelity models to study cancer biology and develop novel precision medicine therapeutics. However, utilizing TOs for systems-biology-based approaches has been limited by a lack of scalable and reproducible methods to develop and profile these models. We describe a robust pan-cancer TO platform with chemically defined media optimized on cultures acquired from over 1,000 patients. Crucially, we demonstrate tumor genetic and transcriptomic concordance utilizing this approach and further optimize defined minimal media for organoid initiation and propagation. Additionally, we demonstrate a neural-network-based high-throughput approach for label-free, light-microscopy-based drug assays capable of predicting patient-specific heterogeneity in drug responses with applicability across solid cancers. The pan-cancer platform, molecular data, and neural-network-based drug assay serve as resources to accelerate the broad implementation of organoid models in precision medicine research and personalized therapeutic profiling programs.

How narrative source impacts convergence of ratings from the Social Cognition and Object Relations Scale-Global Rating Method with psychotherapy process measures.

This study examines the construct validity of the Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Westen, 1995; see also Stein & Mulford, 2018) by exploring the degree of convergence across different narrative sources (i.e., early memories [EM] and psychotherapy narratives [PT]) in relation to patient- and therapist-rated psychotherapy process measures. Using a university-based outpatient sample (n = 81), we found limited convergence for SCORS-G ratings across narrative type. First, paired t tests showed that the means for six of the eight SCORS-G dimensions differed significantly between the EM and PT narratives with the majority having a large magnitude of effect. Moreover, despite 29 significant correlations between a SCORS-G dimension and either an alliance or session quality variable, only two of the eight SCORS-G dimensions significantly correlated with the same process variable across narrative type (e.g., patient-rated session depth with SCORS-G Self Esteem [SE] and Identity and Coherence of Self [ICS]). Importantly, the high degree of theoretical coherence in the associations that emerged between the SCORS-G dimensions and the process variables suggest that the lack of convergence was not due to limited validity of the SCORS-G. Instead, the results underscore the importance of multi-method assessment techniques by highlighting that the manner in which a narrative is elicited will impact the object relational content patients provide. Future research and clinical implications related to the SCORS-G, alliance and psychotherapy process are discussed.

Card pull effects of the Thematic Apperception Test using the Social Cognition and Object Relations-Global Rating Method on complex psychiatric sample.

In recent years, there has been growing interest in examining the stimulus pull effects on respondent narratives to the Thematic Apperception Test (Murray, 1943) using standardized coding methods such as the Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Stein, Hilsenroth, Slavin-Mulford, & Pinsker, 2011; Westen, 1995). The present study expands on prior work by examining sources of variance in SCORS-G dimensions and card pull effect patterns in an adult clinical sample characterized by high psychiatric comorbidity and clinical severity. A sample of 158 adult psychiatric patients in long-term residential treatment provided narratives to 10 TAT cards (five of which have not previously been studied for pull effects). Cards 2 and 7BM pulled for significantly more adaptive narratives (positive pull), whereas Card 13MF pulled for more pathological stories (negative pull). Like prior studies, variance in cognitive dimensions of the SCORS-G was most explained by person effects, whereas the largest source of variance for all other dimensions was best explained by a combination of the card and the person effects on the narrative. Finally, exploratory analyses of card pull effects within different gender groups were conducted. The implications of these findings for performance-based future studies and possible clinical applications of card pull findings are discussed.

Sex-specific differences in peripheral blood leukocyte transcriptional response to LPS are enriched for HLA region and X chromosome genes.

Sex-specific differences in prevalence are well documented for many common, complex diseases, especially for immune-mediated diseases, yet the precise mechanisms through which factors associated with biological sex exert their effects throughout life are not well understood. We interrogated sex-specific transcriptional responses of peripheral blood leukocytes (PBLs) to innate immune stimulation by lipopolysaccharide (LPS) in 46 male and 66 female members of the Hutterite community, who practice a communal lifestyle. We identified 1217 autosomal and 54 X-linked genes with sex-specific responses to LPS, as well as 71 autosomal and one X-linked sex-specific expression quantitative trait loci (eQTLs). Despite a similar proportion of the 15 HLA genes responding to LPS compared to all expressed autosomal genes, there was a significant over-representation of genes with sex by treatment interactions among HLA genes. We also observed an enrichment of sex-specific differentially expressed genes in response to LPS for X-linked genes compared to autosomal genes, suggesting that HLA and X-linked genes may disproportionately contribute to sex disparities in risk for immune-mediated diseases.

External correlates of the SPECTRA: Indices of psychopathology (SPECTRA) in a clinical sample.

The SPECTRA: Indices of Psychopathology is a broadband assessment inventory compatible with contemporary hierarchical models of psychopathology (internalizing, externalizing, reality impairing dimensions and global psychopathology factor). This study explored the SPECTRA's construct validity using a wide range of life event (extra-test) variables in a clinical sample. The life event variables included the following: education level, school failure, childhood adversity, suicide attempts, psychiatric hospitalizations, depression, psychotic symptoms, self-injury, substance abuse, arrests, physical violence, marital status, employment status and current medications. Results showed that all SPECTRA clinical scales had significant life event correlations. For the higher-order Spectra scales, the global index of psychopathology had the greatest number and range of life event correlations. Correlations for the externalizing and reality impairing Spectra scales provided solid validity evidence, while correlations for the internalizing Spectra scale were more diffuse. These findings provide the first non-test-based evidence of construct validity for the SPECTRA.

Do Patterns and Types of Negative Affect During Hospitalization Predict Short-Term Post-Discharge Suicidal Thoughts and Behaviors?

We still have little understanding of short-term predictors of suicidal thoughts and behaviors (STBs). Prior research links increased negative affect to STBs, but the vast majority of earlier work is limited by measuring negative affect at one time point and aiming to predict STBs months or years in the future. Recently, intensive longitudinal studies have shown that negative affect is associated with suicidal thoughts over relatively short, clinically useful time periods; however, the specific patterns and types of negative affect that predict STBs remain unclear. Using ecological momentary assessment (EMA) data from psychiatric inpatients hospitalized for suicide risk (N = 83), this study sought to test whether the patterns (means and variability) of two types of negative affect (anxiety/agitation and shame/self-hatred, which were derived from a larger EMA battery) during hospitalization predict STBs in the four weeks after discharge: an extremely high-risk time for suicidal behavior. The mean - but not the variability - of both anxiety/agitation and shame/self-hatred during hospitalization predicted the number of days with suicidal thoughts after discharge. The mean and the variability of shame/self-hatred - but not anxiety/agitation - predicted post-discharge suicide attempt. We discuss implications for assessment and treatment of suicidal individuals and propose key directions for future research.