Differential Kinetics of Immune Responses Elicited by Covid-19 Vaccines

To the Editor: Previous studies have shown that the BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson–Janssen) vaccines provide robust protective efficacy against coronavirus disease 2019 (Covid-19). Here, we report comparative kinetics of humoral and cellular immune responses elicited by the two-dose BNT162b2 vaccine (in 31 participants), the two-dose mRNA-1273 vaccine (in 22 participants), and the one-dose Ad26.COV2.S vaccine (in 8 participants). We evaluated antibody and T-cell responses from peak immunity at 2 to 4 weeks after the second immunization in recipients of the messenger RNA (mRNA) vaccines or after the first immunization in recipients of the Ad26.COV2.S vaccine to 8 months (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org)

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

The Associations of Adolescent Invulnerability and Narcissism With Problem Behaviors

This study examined the correlations between invulnerability, narcissism, self-esteem, delinquency, and aggression in a sample of at-risk adolescents. Participants were 213, 16-18 year-olds (169 male, 44 female). As expected, narcissism and invulnerability were related to delinquency and aggression. However, maladaptive narcissism predicted unique variance in delinquency and relational aggression. A negative effect for self-esteem emerged for predicting delinquency when controlling for narcissism and perceived invulnerability. The distributions of narcissism and invulnerability indicated that these constructs may not, as a rule, be elevated in such youth. Some preliminary implications for the role of these variables in adolescent problem behaviors are presented. (C) 2009 Elsevier Ltd. All rights reserved

Conduct Disorders

Disruptive behaviors-defined here as behaviors that are associated with diagnoses of Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD)-are the most common reason for referral to mental health services for children and adolescents (Kazdin, 2003). The behaviors that comprise these diagnoses include argumentativeness, temper tantrums, often being angry or resentful, lying, stealing, hurting or threatening to hurt others, cruelty to animals, setting fires, and destruction of property (American Psychiatric Association, 2000). Kazdin (2003) estimates conservatively that between 1.4 million to 4.2 million children in the United States meet criteria for CD alone. Conduct problems or other externalizing behavioral difficulties constitute the most common referral issues for children and adolescents for mental health services (Brinkmeyer & Eyberg, 2003). The presence of these symptoms can be detected early in childhood (Webster-Stratton & Reid, 2003), making them amenable to treatment as long as candidates for intervention are identified and followed through with the prescribed treatment recommendations. ODD and CD encompass a broad array of acts, and young person need not exhibit all, or even most, of the symptoms of ODD and CD to warrant a diagnosis or be a candidate for intervention. Noncompliant behavior is frequently demonstrated in children with ODD or CD; however, many parents whose children do not meet diagnostic criteria for these disorders commonly report seeking outpatient mental health services for noncompliance in their children (McMahon & Forehand, 2003). One of the initial symptoms of conduct problems to emerge in children is lying (Christophersen & Mortweet, 2001). Specific behaviors that are associated with ODD and CD may in and of themselves be reason referring a young person for treatment, including bullying, rigidity/stubbornness, and temper tantrums (Christophersen & Mortweet, 2001; McMahon & Forehand, 2003). © 2009 Springer New York

Variance of gene expression identifies altered network constraints in neurological disease

Gene expression analysis has become a ubiquitous tool for studying a wide range of human diseases. In a typical analysis we compare distinct phenotypic groups and attempt to identify genes that are, on average, significantly different between them. Here we describe an innovative approach to the analysis of gene expression data, one that identifies differences in expression variance between groups as an informative metric of the group phenotype. We find that genes with different expression variance profiles are not randomly distributed across cell signaling networks. Genes with low-expression variance, or higher constraint, are significantly more connected to other network members and tend to function as core members of signal transduction pathways. Genes with higher expression variance have fewer network connections and also tend to sit on the periphery of the cell. Using neural stem cells derived from patients suffering from Schizophrenia (SZ), Parkinson's disease (PD), and a healthy control group, we find marked differences in expression variance in cell signaling pathways that shed new light on potential mechanisms associated with these diverse neurological disorders. In particular, we find that expression variance of core networks in the SZ patient group was considerably constrained, while in contrast the PD patient group demonstrated much greater variance than expected. One hypothesis is that diminished variance in SZ patients corresponds to an increased degree of constraint in these pathways and a corresponding reduction in robustness of the stem cell networks. These results underscore the role that variation plays in biological systems and suggest that analysis of expression variance is far more important in disease than previously recognized. Furthermore, modeling patterns of variability in gene expression could fundamentally alter the way in which we think about how cellular networks are affected by disease processes