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Using a between-subject 3 × 3 design of an experimentally manipulated realistic case vignette of Black, White, and Hispanic youth in a survey mailed to 1540 experienced psychologists, psychiatrists, and social workers, the authors examined if clinicians alter their judgments about treatment for antisocially behaving youth based on the symptom’s social context (e.g., life circumstances) and the youth’s race or ethnicity, even among youth who are otherwise identical in terms of behavioral symptoms. Vignettes describe behaviors meeting DSM-IV criteria for conduct disorder, but contain contextual information suggesting either internal dysfunction (ID) or a normal response to a difficult environment [i.e., environmental-reaction (ER)]. Comparison was symptom-only (SO). Judgments of effectiveness of 14 treatments for youth exhibiting antisocial behavior were examined. Frequencies and median scores of perceived effectiveness level (1–9, Likert) were compared in bivariate analyses, stratifying context and youth’s race or ethnicity. The context of the behavior was associated significantly with differences in effectiveness judgments in 13 of 14 treatments. Within ID and ER contexts, clinicians judged three different treatments as effective (median ≥ 7 of 9). In the SO condition, clinicians were less selective, judging six as effective. In the ID context, psychiatric medications, systems oriented family therapy, and residential care were judged more effective for White than for Black or Hispanic youth. Evidence-based practice research may be hampered by inattention to the social context of behavioral symptoms. Context may activate implicit racial assumptions about treatment effectiveness. Implications are for clinical training to improve service delivery, and future clinical research.

Are mental health clinicians guided by the injunctions of theDiagnostic and Statistical Manual of Mental Disorders(DSM) in making judgments of mental disorder in youth engaging in antisocial behavior? The DSM requires clinicians making a judgment of mental disorder to first make complex mediating inferences about internal dysfunction and rule out the possibility that behaviors are normal reactions to a problematic environment. Responding to a case vignette in which the social context of antisocial behavior was systematically varied, a sample of 1,500 social workers, psychologists, and psychiatrists made judgments about the presence of mental disorder, internal dysfunction, and normality in the antisocial behavior of a youth. Perceptions about the presence of internal dysfunction and normality are found to be related to judgments of mental disorder, but they do not fully mediate the relationship between the influence of social context and judgments of mental disorder.

Background: Conduct disorder (CD) must be distinguished from nondisordered delinquent behaviour to avoid false positives, especially when diagnosing youth from difficult environments. However, the nature of this distinction remains controversial. The DSM-IV observes that its own syndromal CD diagnostic criteria conflict with its definition of mental disorder, which requires that symptoms be considered a manifestation of internal dysfunction to warrant disorder diagnosis. Previous research indicates that professional judgments tend to be guided by the dysfunction requirement, not syndromal symptoms alone. However, there are almost no data on lay conceptualizations. Thus it remains unknown whether judgments about CD are anchored in a broadly shared understanding of mental disorder that provides a basis for professional–lay consensus. Objective: The present study tests which conception of CD, syndromal-symptoms or dysfunction-requirement, corresponds most closely to lay judgments of disorder or nondisorder and compares lay and professional judgments. We hypothesized that lay disorder judgments, like professional judgments, tend to presuppose the dysfunction requirement. Method: Three lay samples (nonclinical social workers, nonpsychiatric nurses, and undergraduates) rated their agreement that youths described in clinical vignettes have a mental disorder. All vignettes satisfied DSM-IV CD diagnostic criteria. Vignettes were varied to present syndromal symptoms only, symptoms suggesting internal dysfunction, and symptoms resulting from reactions to negative circumstances, without dysfunction. Results: All lay samples attributed disorder more often to youths whose symptoms suggested internal dysfunction than to youths with similar symptoms but without a likely dysfunction. Conclusions: The dysfunction requirement appears to reflect a widely shared lay and professional concept of disorder.

We examine biases in social workers' assessment of antisocial youths based on the responses of 250 MSW students to clinical case vignettes describing youths engaging in antisocial behavior, all of whom satisfied theDiagnostic and Statistical Manual of Mental Disorders,fourth edition, criteria for conduct disorder. Respondents were to judge whether the described youth had a psychiatric or mental disorder. We manipulated the content of the vignettes to suggest either internal dysfunction (i.e., disorder) or a normal response to a difficult environment (i.e., nondisorder) as the cause of the antisocial behavior. Contrary to the claims of critics, respondents generally appropriately distinguished, based on contextual information, between disordered and nondisordered youth. However, a minority of students did appear to display bias, primarily in the direction of underdiagnosis of disorder.

This study investigated whether the current system of psychiatric classification can validly distinguish mental disorders from non-disordered problems in living. A core assumption of the DSM (1994, APA) classification system is that elements of disorder can be captured by the presence of specific operationalized syndromes, or sets of co-occurring symptoms, based on symptom counts, severity, duration, and impaired functioning, and that this can be adequately achieved independent of the social context in which the behavioral symptoms occur. The validity of this assumption was tested using the judgments of experienced mental health clinicians. We hypothesized that an identical set of adolescent antisocial behaviors, meeting the DSM-IV diagnostic criteria for Conduct Disorder, would be judged by experienced clinicians as indicative of disorder or non-disorder, depending on the social context in which the behaviors occur. A representative sample of 483 psychiatrists, 603 psychologists, and 454 social workers read a vignette depicting adolescent antisocial behavior, and responded to questions concerning its nature, cause, and response to various mental health interventions. In these vignettes, the features of the behavioral pattern were held constant, while the situational context in which the behavior occurred was systematically altered. Results supported our hypothesis. Under certain situational circumstances, a youth may exhibit behaviors that clearly meet the DSM-IV diagnostic criteria for Conduct Disorder, but does not have a mental disorder, according to the view of experienced clinicians. In addition, clinicians reached different judgments about course, etiology, and treatment responsiveness when the same adolescent antisocial behavior occurred in different situational contexts. Our findings raise questions about the validity of classification systems based on behavioral criteria independent of their social context. Implications of findings are discussed.

We examine biases in social workers' assessment of antisocial youths based on the responses of 250 MSW students to clinical case vignettes describing youths engaging in antisocial behavior, all of whom satisfied the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for conduct disorder. Respondents were to judge whether the described youth had a psychiatric or mental disorder.

Neurodevelopmental proteasomopathies are a group of disorders caused by variants in proteasome subunit genes, that disrupt protein homeostasis and brain development through poorly characterized mechanisms. Here, we report 26 distinct variants in PSMC5 , encoding the AAA⁺ ATPase subunit PSMC5/RPT6, in individuals with syndromic neurodevelopmental conditions. Combining genetic, multi-omics and biochemical approaches across cellular models and Drosophila , we unveil the essential role of proteasomes in sustaining key cellular processes. Loss of PSMC5/RPT6 function impairs proteasome activity, leading to protein aggregation, disruption of mitochondrial homeostasis, and dysregulation of lipid metabolism and immune signaling. It also compromises synaptic balance, neuritogenesis, and neural progenitor cell stemness, causing deficits in higher-order functions, including learning and locomotion. Pharmacological targeting of integrated stress response kinases reveals a mechanistic link between proteotoxic stress and spontaneous type I interferon activation. These findings expand our understanding of proteasome-dependent quality control in neurodevelopment and suggest potential therapeutic strategies for neurodevelopmental proteasomopathies. Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Understanding the ability of SARS-CoV-2 vaccine-elicited antibodies to neutralize and protect against emerging variants of concern and other sarbecoviruses is key for guiding vaccine development decisions and public health policies. We show that a clinical stage multivalent SARS-CoV-2 receptor-binding domain nanoparticle vaccine (SARS-CoV-2 RBD-NP) protects mice from SARS-CoV-2-induced disease after a single shot, indicating that the vaccine could allow dose-sparing. SARS-CoV-2 RBD-NP elicits high antibody titers in two non-human primate (NHP) models against multiple distinct RBD antigenic sites known to be recognized by neutralizing antibodies. We benchmarked NHP serum neutralizing activity elicited by RBD-NP against a lead prefusion-stabilized SARS-CoV-2 spike immunogen using a panel of single-residue spike mutants detected in clinical isolates as well as the B.1.1.7 and B.1.351 variants of concern. Polyclonal antibodies elicited by both vaccines are resilient to most RBD mutations tested, but the E484K substitution has similar negative consequences for neutralization, and exhibit modest but comparable neutralization breadth against distantly related sarbecoviruses. We demonstrate that mosaic and cocktail sarbecovirus RBD-NPs elicit broad sarbecovirus neutralizing activity, including against the SARS-CoV-2 B.1.351 variant, and protect mice against severe SARS-CoV challenge even in the absence of the SARS-CoV RBD in the vaccine. This study provides proof of principle that sarbecovirus RBD-NPs induce heterotypic protection and enables advancement of broadly protective sarbecovirus vaccines to the clinic.

When social workers judge that an antisocially behaving adolescent has a mental disorder, what are the implications of that attribution for other clinical judgments about the youth? Clinical case vignettes that satisfied DSM-IV diagnostic criteria for conduct disorder were presented to 250 MSW students. Based on DSM-IV guidelines and on the “harmful dysfunction” analysis of the concept of mental disorder, the context of the symptoms presented in the vignettes was manipulated experimentally to suggest either internal dysfunction or a normal response to a difficult environment as the cause of the youth's antisocial behavior. Students were asked to judge whether the youth had a psychiatric disorder and to assess prognosis, need for professional help, and appropriateness of medication.

Since the ALMA North America Prototype Antenna was awarded to the Smithsonian Astrophysical Observatory (SAO), SAO and the Academia Sinica Institute of Astronomy & Astrophysics (ASIAA) are working jointly to relocate the antenna to Greenland. This paper shows the status of the antenna retrofit and the work carried out after the recommissioning and subsequent disassembly of the antenna at the VLA has taken place. The next coming months will see the start of the antenna reassembly at Thule Air Base. These activities are expected to last until the fall of 2017 when commissioning should take place. In parallel, design, fabrication and testing of the last components are taking place in Taiwan.