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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.

T1 Figure 1ConclusionsOverall, this largest paediatric single cell COVID-19 study to date showed significant differences in response to SARS-CoV-2 between children and adults, reflecting the changes of the immune landscape over developmental time, which in children are dominated by naive and innate responses.

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatricversusadult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data1as a highly granular reference for the study of immune responses in airways and blood in children.

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.

Low success rates during drug development are due, in part, to the difficulty of defining drug mechanism‐of‐action and molecular markers of therapeutic activity. Here, we integrated 199,219 drug sensitivity measurements for 397 unique anti‐cancer drugs with genome‐wide CRISPR loss‐of‐function screens in 484 cell lines to systematically investigate cellular drug mechanism‐of‐action. We observed an enrichment for positive associations between the profile of drug sensitivity and knockout of a drug's nominal target, and by leveraging protein–protein networks, we identified pathways underpinning drug sensitivity. This revealed an unappreciated positive association between mitochondrial E3 ubiquitin–protein ligase MARCH5 dependency and sensitivity to MCL1 inhibitors in breast cancer cell lines. We also estimated drug on‐target and off‐target activity, informing on specificity, potency and toxicity. Linking drug and gene dependency together with genomic data sets uncovered contexts in which molecular networks when perturbed mediate cancer cell loss‐of‐fitness and thereby provide independent and orthogonal evidence of biomarkers for drug development. This study illustrates how integrating cell line drug sensitivity with CRISPR loss‐of‐function screens can elucidate mechanism‐of‐action to advance drug development.

Financial support for the analyses was from grants from the Natural Sciences and Engineering Research Council Discovery program, the Canada Foundation for Innovation and the Ontario Innovation Trust (TKK, NPJ)

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.

Background Adolescents account for 1 in 4 sexually transmitted infections (STIs) diagnosed annually in the United States. Many adolescents seek care in emergency departments (ED) for acute medical problems which offers an opportunity to screen for risk behaviors including sexual health. As emergency medicine provider time is focused on the acute medical problem, using technology may be an acceptable and effective alternative to identify and decrease screening risky sexual behaviors. Methods Adolescents aged 13–18 years participated in a randomized controlled trial of an electronic health behavior screening and feedback tool in a pediatric emergency department. All participants were surveyed about risky behaviors at the baseline ED visit and 3 months later, and only intervention arm participants received immediate individualized electronic feedback about their risk behaviors, normative comparisons and brief educational information, including on birth control and condoms. In this secondary analysis, we used Chi-squared analyses to compare differences in 3-month STI risk defined as sexually active and reporting inconsistent condom use. Results A total of 296 adolescents including 55% females enrolled in the study with 72% (n=212) completing the 3 month follow-up survey. At baseline 23% (69/296) reported ever having sex and 67% (46/69) reported using a condom at last sex. At follow-up 16% (17/105) of the intervention group and 23% (25/107) of controls reported having sex in the last 3 months. Of those sexually active, 35% (6/17) of intervention group compared to 56% (14/25) of control group reported not always using condoms in the last 3 months (p=0.19). STI risk at 3 months was 6% (6/105) for intervention participants compared to 13% (14/107) for controls (p=0.07). Conclusion Electronic sexual health screening in the emergency department increases opportunities to assess, identify, and intervene in risky sexual behaviors in adolescents and may contribute to a decrease in risky behaviors. Disclosure No significant relationships.

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.

Handling a rodent disease outbreak in a facility can be a challenge. After the University of Colorado Denver Office of Laboratory Animal Resources enhanced its sentinel monitoring program, > 90% of the animal colonies housed in a vivarium at the Anschutz Medical Campus (with an area of 50,000 net ft(2)), serving the labs of > 250 principal investigators, tested positive for multiple infective agents including mouse parvovirus, fur mites, pinworms and epizootic diarrhea of infant mice. The authors detail the process by which they planned and executed a shutdown and a decontamination of the facility, which involved the rederivation or cryopreservation of > 400 unique genetically modified mouse lines. The authors discuss the aspects of the project that were successful as well as those that could have been improved.

A systematic review of the literature was conducted to investigate what is currently known about support for social participation for adults with autism spectrum disorders (ASD). A computerized database search followed by hand searching was conducted to locate empirical studies published after 1995 in peer-reviewed journals that described social participation or social support for adults with ASD. 14 studies were identified, evaluated for strength of evidence, and organized into topical themes. These studies focused on support for social participation from two perspectives: social functioning and quality of life (QoL). Supporting social functioning and social participation is important, as this is one route through which individuals with ASD may be able to form relationships and establish natural support networks, which can in turn contribute to QoL. In addition, working to improve social skills is of key importance as social functioning heavily impacts outcomes in a variety of areas. Social participation, social functioning, and QoL for adults with ASD appear to be facilitated through informal social support from social networks, participation in social skills groups, and membership in support groups.

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.

© 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