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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.

Introduction: In this study we aimed to assess the impact of an electronic health assessment with individualized feedback for risk behaviors in adolescents seeking care in a pediatric emergency department (ED). Methods: We conducted a randomized control trial using a tablet-based screening program with a study population of adolescents in a busy pediatric ED. The intervention group received the screening program with individualized feedback. The control group received the screening program without feedback. All participants received one-day and three-month follow-up surveys to assess behaviors and attitudes toward health behaviors. Results: A total of 296 subjects were enrolled and randomized. There was no difference in changes in risky behaviors between the control and experimental groups. A higher proportion of participants in the intervention groups reported that the screener changed the way they thought about their health at one-day follow-up (27.0%, 36/133) compared to the control group (15.5%, 20/129, P = .02). Conclusion: This study successfully tested a multivariable electronic health screener in a real-world setting of a busy pediatric ED. The tool did not significantly change risky health behaviors in the adolescent population screened. However, our finding that the intervention changed adolescents’ perceptions of their health opens a door to the continued development of electronic interventions to screen for and target risk behaviors in adolescents in the ED setting.

The proteome provides unique insights into disease biology beyond the genome and transcriptome. A lack of large proteomic datasets has restricted the identification of new cancer biomarkers. Here, proteomes of 949 cancer cell lines across 28 tissue types are analyzed by mass spectrometry. Deploying a workflow to quantify 8,498 proteins, these data capture evidence of cell-type and post-transcriptional modifications. Integrating multi-omics, drug response, and CRISPR-Cas9 gene essentiality screens with a deep learning-based pipeline reveals thousands of protein biomarkers of cancer vulnerabilities that are not significant at the transcript level. The power of the proteome to predict drug response is very similar to that of the transcriptome. Further, random downsampling to only 1,500 proteins has limited impact on predictive power, consistent with protein networks being highly connected and co-regulated. This pan-cancer proteomic map (ProCan-DepMapSanger) is a comprehensive resource available at https://cellmodelpassports.sanger.ac.uk.

We present a multiomic cell atlas of human lung development that combines single cell RNA and ATAC sequencing, high throughput spatial transcriptomics and single cell imaging. Coupling single cell methods with spatial analysis has allowed a comprehensive cellular survey of the epithelial, mesenchymal, endothelial and erythrocyte/leukocyte compartments from 5-22 post conception weeks. We identify new cell states in all compartments. These include developmental-specific secretory progenitors and a new subtype of neuroendocrine cell related to human small cell lung cancer. Our datasets are available through our web interface (https://lungcellatlas.org). Finally, to illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signalling and transcription factor hierarchies which we test using organoid models.HighlightsSpatiotemporal atlas of human lung development from 5-22 post conception weeks identifies 144 cell types/states.Tracking the developmental origins of multiple cell compartments, including new progenitor states.Functional diversity of fibroblasts in distinct anatomical signalling niches.Resource applied to interrogate and experimentally test the transcription factor code controlling neuroendocrine cell heterogeneity and the origins of small cell lung cancer.

Combinations of anti-cancer drugs can overcome resistance and provide new treatments1,2. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable orKRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stableorKRAS–TP53double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.

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.

Although current sports nutrition recommendations advocate for a high carbohydrate (CHO) intake among endurance athletes, recent research has suggested that training with low CHO availability may augment adaptations to aerobic training. The purpose of this study was to observe the dietary habits of collegiate distance runners and to investigate the effects of habitual CHO intake on aerobic performance [VODuring an 8-week trial period, 12 (N = 12) collegiate track athletes recorded their self-selected dietary intake via 24-hour recall. Analysis of CHO intake was conducted by a registered dietitian. Pre [VOThe average CHO was 4.11 ± 1.03 g/kg body mass (BM), with only one female athlete meeting dietary recommendations, consuming ≥ 6 g/kg BM. Male distance runners on average had a lower CHO than females. After adjusting for VOCollegiate distance runners exhibited marked improvements in maximal aerobic capacity during the in-season while consuming a marginally low-CHO diet, with a predominant effect in males. Therefore, CHO intakes below current recommendations for endurance athletes might not be detrimental to aerobic training adaptations.

The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G) measures the quality of object relations in narrative material. The reliability and validity of this measure have been well established. However, a psychometric oddity of this scale is that default ratings are given to select dimensions when the relevant construct is not present. This can result in narrative 'blandness' and may impact clinical findings. The aim of these two studies is to understand these phenomena both psychometrically and clinically. In the first study, we identified 276 outpatients who had SCORS-G ratings for TAT Cards 1, 2, 3BM, and 14, set criteria for narrative 'blandness' across all eight dimensions, and examined group differences. In Study 2, we used a subset (N = 99) of Study 1 and examined how percentage of formal default ratings for Emotional Investment in Values and Moral Standards (EIM), Experience and Management of Aggressive Impulses (AGG), Self-Esteem(SE), and Identify and Coherence of Self (ICS) impacted robustness of correlations across tests of intelligence, psychopathology, and normal personality functioning. Taken together, we identified clinical characteristics of patients who are more likely to produce 'bland' narratives and increased percentages of formal default ratings. Also, an excess of default ratings per protocol impacts robustness of correlations and weakens significant correlations. As cut-off scores increase (>25% and >28.12%), the likelihood of being able to interpret EIM, AGG, SE, and ICS decreases. Psychometric and clinical implications are discussed.

Background Employment is a key determinant in quality of life. However, less than 50% of adults with ASD are employed. Objective In order to better support community-based employment for persons with ASD who use augmentative and alternative communication (AAC), there is a need to better understand those situations in which successful outcomes have been achieved. Method This study utilized a multiple case design to investigate the experiences of seven individuals with ASD who use AAC and are successfully employed in the community. Results Results provide evidence that individuals with ASD who use AAC can be successfully employed, when provided with appropriate supports. Expressive and receptive communication were commonly identified as challenges, however, mobile devices provided support to communication and participation for many of the participants with ASD. Conclusions Results from the current study provide evidence that successful employment for individuals with ASD who use AAC is possible when intervention addresses three key areas: the development of skills that are valued in the workplace, the identification and creation of good job matches, and access to needed supports.

The current study sought to develop and validate a new measure of chronic suicide risk (the S_Chron) from the Personality Assessment Inventory in a mixed sample of psychiatric inpatients and outpatients. In an initial development sample (N=397), hierarchical logistic regression identified six PAI variables uniquely associated with multiple versus single/no prior suicide attempts after controlling for sample demographics: Negative Impression Management, Situational Stress, Mania - Grandiosity, Borderline - Negative Relationships, Borderline - Self-Harm, and Antisocial Behaviors. These indicators were then aggregated into a single index (S_Chron) and evaluated in terms of validity in an independent clinical sample (N=398). Results indicated the S_Chron effectively differentiated between groups with multiple versus single/no prior suicide attempts, even after controlling for the effects of the PAI Suicidal Ideation (SUI) and Suicide Potential (SPI) indices, with moderate to large effect sizes observed (range of Cohen's d's=0.30-0.91). Further, the S_Chron incremented all other PAI indices and SUI in predicting multiple suicide attempts. The potential clinical application and ways in which the S_Chron may augment other existing measures of suicide risk are discussed.

The purpose of this project was to understand the hopes of parents with children with ASD. Particularly understudied are the hopes parents have for long-term outcomes for their child. A cross-sectional focus group design was used and six focus groups were completed. These groups included parents of (1) preschool aged children who were recently diagnosed, (2) children in early elementary school, (3) children in later elementary school, (4) children in middle school, (5) children in high school, and (6) children who are adults with ASD. Results indicated 77.4% of the data were devoted to hopes for the children's independence, happiness, and skill improvement; increased authentic socially significant relationships; and future employment.

Background and Purpose— Faster treatment with intravenous tissue-type plasminogen activator (tPA) is likely to improve outcomes. Optimizing prehospital triage by mobile stroke units (MSUs) may speed treatment times. The Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit (BEST-MSU) study was launched in May 2014 using the first MSU in the United States to compare stroke management using an MSU versus standard management (SM). Herein, we describe the results of the prespecified, nonrandomized run-in phase designed to obtain preliminary data on study logistics. Methods— The run-in phase consisted of 8 MSU weeks when all-patient care occurred on the MSU and 2 SM weeks when the MSU nurse met personnel on scene or at the emergency department to ensure comparability with MSU patients. Telemedicine was independently performed in 9 MSU cases. Results— Of 130 alerts, 24 MSU and 2 SM patients were enrolled. Twelve of 24 MSU patients received tPA on board; 4 were treated within 60 minutes of last seen normal, and 4 went on to endovascular treatment. There were no hemorrhagic complications. Four had primary intracerebral hemorrhage. Agreement on tPA eligibility between the onsite and telemedicine physician was 90%. Conclusions— The run-in phase provided a tPA treatment rate of 1.5 patients per week, assured us that treatment within 60 minutes of onset is possible, and enabled enrollment of patients on SM weeks. We also recognized the opportunity to assess the effect of the MSU on endovascular treatment and intracerebral hemorrhage. Challenges include the need to control biased patient selection on MSU versus SM weeks and establish inter-rater agreement for tPA treatment using telemedicine.

Summary Obesity is a steadily growing epidemic affecting all segments of the population including college-aged students. The weight gain that is evidenced amid the transitional stage of college years increases the risks associated with cardiovascular and metabolic diseases. The BodyMetrix® BX-2000 (ULTRA) using a seven-site method has been evaluated against dual-energy X-ray absorptiometry (DXA) for estimation of body composition, which has yielded conflicting results. To date, no studies have compared the three-site method Jackson and Pollock three-site method to DXA. Purpose The purpose of the study was twofold (i) to compare agreement between Jackson–Pollock seven site (JP7), Jackson–Pollock three site (JP3) and Pollock three site (P3) to predict body fat (%BF) using ULTRA and (ii) and to compare the three ULTRA methodologies against DXA. Methods Seventy-six healthy college-aged subjects (ages = 22·08 ± 2·50 years) participated in this study. DXA and ULTRA body composition assessments were performed following manufacturer's instructions to estimate %BF. Paired sample t-tests were used to assess agreement between JP7, P3 and JP3. Additionally, a two-tailed sample t-test was performed by sex. ULTRA and DXA results were also performed for agreement and bivariate correlation. Results No significant differences between JP7 and P3, P = 0·38, were observed. In males, no significant differences were observed between JP7 and P3, P = 0·18. Significant differences were observed in all other pairs, P≤0·001 and between ULTRA and DXA. Conclusions The Pollock 3-site method estimates body fat percentage with comparable accuracy to JP7 using ULTRA.

Research has indicated that as many as 10% to 15% of primary care patients have symptoms that are not well explained medically. These patients could be labeled as "somatizers." This study assessed the extent to which underlying psychological characteristics contribute to a person's level of somatization and service utilization. The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G; Stein, Hilsenroth, Slavin-Mulford, & Pinsker, 2011; Westen, 1995) was used to rate early memory narratives of 100 patients in a suburban primary care setting. Using principal axis factoring, the SCORS-G was divided into 2 components and these components (cognitive and affective) were used in subsequent analyses. The affective component was significantly negatively correlated with 2 measures of somatization and positively related to physician ratings of global health. The affective component also showed a trend toward significance on overnight hospital stays and patient-rated health. The cognitive component showed a trend toward significance with both measures of somatization, but it was not correlated with other measures of health. This study demonstrates the value of assessing underlying processes (via SCORS-G ratings of early memory narratives) that contribute to increased rates of somatization and health care utilization. Clinical implications for the relationship between affect and physical health are explored.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Karliner, Westrich, Shedler, and Mayman (1996) developed the Early Memory Index (EMI) to assess mental health, narrative coherence, and traumatic experiences in reports of early memories. We assessed the convergent validity of EMI scales with data from 103 women from an urban primary care clinic (Study 1) and data from 48 women and 24 men from a suburban primary care clinic (Study 2). Patients provided early memory narratives and completed self-report measures of psychopathology, trauma, and health care utilization. In both studies, lower scores on the Mental Health scale and higher scores on the Traumatic Experiences scale were related to higher scores on measures of psychopathology and childhood trauma. Less consistent associations were found between the Mental Health and Traumatic Experiences scores and measures of health care utilization. The Narrative Coherence scale showed inconsistent relationships across measures in both samples. In analyses assessing the overall fit between hypothesized and actual correlations between EMI scores and measures of psychopathology, severity of trauma symptoms, and health care utilization, the Mental Health scale of the EMI demonstrated stronger convergent validity than the EMI Traumatic Experiences scale. The results provide support for the convergent validity of the Mental Health scale of the EMI.

For at-risk (single parent, low income, low support) mothers, healthy adaptation and the ability to manage stress have clear implications for parenting and the social-emotional well-being of their young offspring. The purpose of this longitudinal study was to examine associations between defense mechanisms in pregnant women and their toddlers' attachment security, social-emotional, and behavioral adjustment.Participants were 84 pregnant women during their last trimester of pregnancy, recruited from community agencies primarily serving low-income families. Women were followed prospectively from pregnancy through 2 years after birth and completed several multimethod assessments during that period. Observations of mother-child interactions were also coded after the postnatal visits.Multiple regression analyses revealed that mothers' defense mechanisms were significantly associated with several toddler outcomes. Mature, healthy defenses were significantly associated with greater toddler attachment security and social-emotional competence and fewer behavior problems, and less mature defenses (disavowal in particular) were associated with lower levels of attachment security and social-emotional competence. Associations remained significant, or were only slightly attenuated, after controlling for demographic variables and partner abuse during pregnancy.The study findings suggest that defensive functioning in parents preparing for and parenting toddlers influences the parent-child attachment relationship and social-emotional adjustment in the earliest years of life. Possible mechanisms for these associations may include parental attunement and mentalization, as well as specific caregiving behavior toward the child. Defensive functioning during times of increased stress (such as the prenatal to postnatal period) may be especially important for understanding parental influences on the child.

Awareness of effective weight management strategies is necessary to prepare exercise science students for future work with obesity. Exercise science faculty members developed a course related to exercise as a therapeutic tool and options available for weight loss. The purpose of the present study was to investigate student views of weight management and obesity, which can be a difficult task using traditional methods such as Likert scale surveys. To investigate student views relative to the course content, Q methodology, which is a mixed-method research approach, was used at the beginning and end of the course. Students completed a Q sort, ranking 44 statements related to obesity in accordance to their own points of view. The pretest/posttest design enabled an opportunity to determine if course goals were accomplished and if student perceptions related to obesity were transformed. Factor analysis of precourse sorts revealed that students possessed a naïve singular view of weight-related concepts. Analysis of sorts at course completion resulted in a two-factor solution revealing changes in perspective; some students took on a health professional type of view, whereas others demonstrated antifat views. In conclusion, the findings revealed key variables that should be addressed in curricula involving therapeutic obesity interventions. An improved curriculum based on these results should better encourage students to develop a broad comprehension of multifactorial causes and treatment for weight management and obesity. Implementing the use of Q methodology may serve as a valuable asset to measure and evaluate subjectivity of obesity discrimination. Antifat attitudes among exercise science students may influence future clients' potential achievements.

© 2014, Springer Science+Business Media New York. Leadership development is a core value of Maternal Child Health Bureau training programs. Mentorship, an MCH Leadership Competency, has been shown to positively affect career advancement and research productivity. Improving mentorship opportunities for junior faculty and trainees may increase pursuit of careers in areas such as adolescent health research and facilitate the development of new leaders in the field. Using a framework of Developmental Networks, a group of MCH Leadership Education in Adolescent Health training program faculty developed a pilot mentoring program offered at the Society for Adolescent Health and Medicine Annual Meeting (2011–2013). The program matched ten interdisciplinary adolescent health fellows and junior faculty with senior mentors at other institutions with expertise in the mentee’s content area of study in 2011. Participants were surveyed over 2 years. Respondents indicated they were “very satisfied” with their mentor match, and all agreed or strongly agreed that the mentoring process in the session was helpful, and that the mentoring relationships resulted in several ongoing collaborations and expanded their Developmental Networks. These results demonstrate that MCH programs can apply innovative strategies to disseminate the MCH Leadership Competencies to groups beyond MCH-funded training programs through programs at scientific meetings. Such innovations may enhance the structure of mentoring, further the development of new leaders in the field, and expand developmental networks to provide support for MCH professionals transitioning to leadership roles.

Ewing's sarcoma is a malignant pediatric bone tumor with a poor prognosis for patients with metastatic or recurrent disease. Ewing's sarcoma cells are acutely hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibition and this is being evaluated in clinical trials, although the mechanism of hypersensitivity has not been directly addressed. PARP inhibitors have efficacy in tumors with BRCA1/2 mutations, which confer deficiency in DNA double-strand break (DSB) repair by homologous recombination (HR). This drives dependence on PARP1/2 due to their function in DNA single-strand break (SSB) repair. PARP inhibitors are also cytotoxic through inhibiting PARP1/2 auto-PARylation, blocking PARP1/2 release from substrate DNA. Here, we show that PARP inhibitor sensitivity in Ewing's sarcoma cells is not through an apparent defect in DNA repair by HR, but through hypersensitivity to trapped PARP1-DNA complexes. This drives accumulation of DNA damage during replication, ultimately leading to apoptosis. We also show that the activity of PARP inhibitors is potentiated by temozolomide in Ewing's sarcoma cells and is associated with enhanced trapping of PARP1-DNA complexes. Furthermore, through mining of large-scale drug sensitivity datasets, we identify a subset of glioma, neuroblastoma and melanoma cell lines as hypersensitive to the combination of temozolomide and PARP inhibition, potentially identifying new avenues for therapeutic intervention. These data provide insights into the anti-cancer activity of PARP inhibitors with implications for the design of treatment for Ewing's sarcoma patients with PARP inhibitors.

Background and Purpose— Recently, the Mobile Stroke Unit (MSU) concept was introduced in Germany demonstrating prehospital treatment of more patients within the first hour of symptom onset. However, the details and complexities of establishing such a program in the United States are unknown. We describe the steps involved in setting up the first MSU in the United States. Methods— Implementation included establishing leadership, fund-raising, purchase and build-out, knitting a collaborative consortium of community stakeholders, writing protocols to ensure accountability, radiation safety, purchasing supplies, licensing, insurance, establishing a base station, developing a communication plan with city Emergency Medical Services, Emergency Medical Service training, staffing, and designing a research protocol. Results— The MSU was introduced after ≈1 year of preparation. Major obstacles to establishing the MSU were primarily obtaining funding, licensure, documenting radiation safety protocols, and establishing a smooth communication system with Emergency Medical Services. During an 8 week run-in phase, ≈2 patients were treated with recombinant tissue-type plasminogen activator per week, one-third within 60 minutes of symptom onset, with no complications. A randomized study to determine clinical outcomes, telemedicine reliability and accuracy, and cost effectiveness was formulated and has begun. Conclusion— The first MSU in the United States has been introduced in Houston, TX. The steps needed to accomplish this are described.

Cell 166(3), 740-754 (2016). doi:10.1016/j.cell.2016.06.017, Published by Elsevier, New York, NY