Determinants of Propranolol’s Selective Effect on Loss Aversion

Research on emotion and decision making has suggested that arousal mediates risky decisions, but several distinct and often confounded processes drive such choices. We used econometric modeling to separate and quantify the unique contributions of loss aversion, risk attitudes, and choice consistency to risky decision making. We administered the beta-blocker propranolol in a double-blind, placebo-controlled within-subjects study, targeting the neurohormonal basis of physiological arousal. Matching our intervention’s pharmacological specificity with a quantitative model delineating decision-making components allowed us to identify the causal relationships between arousal and decision making that do and do not exist. Propranolol selectively reduced loss aversion in a baseline- and dose-dependent manner (i.e., as a function of initial loss aversion and body mass index), and did not affect risk attitudes or choice consistency. These findings provide evidence for a specific, modulatory, and causal relationship between precise components of emotion and risky decision making

The Phenomenology of SUSY models with a Gluino LSP

In this paper we study the experimental consequences of a theory which naturally has a heavy, stable (or almost stable) gluino. We define the boundary conditions at a messenger scale $M \sim 10^{14}$ GeV which lead to this alternative phenomenologically acceptable version of the minimal supersymmetric standard model. In this theory, either the gluino or the gravitino is the lightest supersymmetric particle [LSP]. If the gravitino is the LSP, then the gluino is the next-to-LSP with a lifetime on the order of 100 years. In either case, the gluino is (for all practical purposes) a stable particle with respect to experiments at high energy accelerators. Thus the standard missing energy signature for SUSY fails. A stable gluino forms a color singlet hadron, the lightest of which is assumed to be an isoscalar gluino-gluon bound state ($R_0$). The $R_0$ has strong interactions and will interact in a hadronic calorimeter; depositing some fraction of its kinetic energy. Finally, in the case the gravitino is the LSP, bounds from searches for stable heavy isotopes of hydrogen or oxygen do not apply to the metastable $R_0$.Comment: 34 pages, 16 figures color code

An Observational Study With the Janssen Autism Knowledge Engine (JAKE®) in Individuals With Autism Spectrum Disorder

Objective: The Janssen Autism Knowledge Engine (JAKE®) is a clinical research outcomes assessment system developed to more sensitively measure treatment outcomes and identify subpopulations in autism spectrum disorder (ASD). Here we describe JAKE and present results from its digital phenotyping (My JAKE) and biosensor (JAKE Sense) components.Methods: An observational, non-interventional, prospective study of JAKE in children and adults with ASD was conducted at nine sites in the United States. Feedback on JAKE usability was obtained from caregivers. JAKE Sense included electroencephalography, eye tracking, electrocardiography, electrodermal activity, facial affect analysis, and actigraphy. Caregivers of individuals with ASD reported behaviors using My JAKE. Results from My JAKE and JAKE Sense were compared to traditional ASD symptom measures.Results: Individuals with ASD (N = 144) and a cohort of typically developing (TD) individuals (N = 41) participated in JAKE Sense. Most caregivers reported that overall use and utility of My JAKE was “easy” (69%, 74/108) or “very easy” (74%, 80/108). My JAKE could detect differences in ASD symptoms as measured by traditional methods. The majority of biosensors included in JAKE Sense captured sizable amounts of quality data (i.e., 93–100% of eye tracker, facial affect analysis, and electrocardiogram data was of good quality), demonstrated differences between TD and ASD individuals, and correlated with ASD symptom scales. No significant safety events were reported.Conclusions: My JAKE was viewed as easy or very easy to use by caregivers participating in research outside of a clinical study. My JAKE sensitively measured a broad range of ASD symptoms. JAKE Sense biosensors were well-tolerated. JAKE functioned well when used at clinical sites previously inexperienced with some of the technologies. Lessons from the study will optimize JAKE for use in clinical trials to assess ASD interventions. Additionally, because biosensors were able to detect features differentiating TD and ASD individuals, and also were correlated with standardized symptom scales, these measures could be explored as potential biomarkers for ASD and as endpoints in future clinical studies.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02668991 identifier: NCT0266899

Deletions in the Repertoire of Pseudomonas syringae pv. tomato DC3000 Type III Secretion Effector Genes Reveal Functional Overlap among Effectors

The γ-proteobacterial plant pathogen Pseudomonas syringae pv. tomato DC3000 uses the type III secretion system to inject ca. 28 Avr/Hop effector proteins into plants, which enables the bacterium to grow from low inoculum levels to produce bacterial speck symptoms in tomato, Arabidopsis thaliana, and (when lacking hopQ1-1) Nicotiana benthamiana. The effectors are collectively essential but individually dispensable for the ability of the bacteria to defeat defenses, grow, and produce symptoms in plants. Eighteen of the effector genes are clustered in six genomic islands/islets. Combinatorial deletions involving these clusters and two of the remaining effector genes revealed a redundancy-based structure in the effector repertoire, such that some deletions diminished growth in N. benthamiana only in combination with other deletions. Much of the ability of DC3000 to grow in N. benthamiana was found to be due to five effectors in two redundant-effector groups (REGs), which appear to separately target two high-level processes in plant defense: perception of external pathogen signals (AvrPto and AvrPtoB) and deployment of antimicrobial factors (AvrE, HopM1, HopR1). Further support for the membership of HopR1 in the same REG as AvrE was gained through bioinformatic analysis, revealing the existence of an AvrE/DspA/E/HopR effector superfamily, which has representatives in virtually all groups of proteobacterial plant pathogens that deploy type III effectors

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Data Descriptor: An open resource for transdiagnostic research in pediatric mental health and learning disorders

Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5–21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eyetracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n =664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis

Beta-adrenergic Blockade at Memory Encoding, but Not Retrieval, Decreases the Subjective Sense of Recollection

Humans remember emotional events not only better but also exhibit a qualitatively distinct recollective experience—that is, emotion intensifies the subjective vividness of the memory, the sense of reliving the event, and confidence in the accuracy of the memory [Phelps, E. A., & Sharot, T. How (and why) emotion enhances the subjective sense of recollection. Current Directions in Psychological Science, 17, 147–152, 2008]. Although it has been demonstrated that activation of the betaadrenergic system, linked to increases in stress hormone levels and physiological arousal, mediates enhanced emotional memory accuracy, the mechanism underlying the increased subjective sense of recollection is unknown. Behavioral evidence suggests that increased arousal associated with emotional events, either at encoding or retrieval, underlies their increased subjective sense of recollection. Using a double-blind, placebo-controlled, within-subject design, we showed that reducing arousal at encoding through oral intake of 80-mg of the beta-adrenergic receptor antagonist propranolol decreases the subjective sense of recollection for both negative and neutral stimuli 24 hr later. In contrast, administration of propranolol before memory retrieval did not alter the subjective sense of recollection. These results suggest that the neurohormonal changes underlying increased arousal at the time ofmemory formation, rather than the time of memory retrieval, modulate the subjective sense of recollection

Multimodal Investigations of Reward Circuitry and Anhedonia in Adolescent Depression

&lt;jats:p&gt;Depression is a highly prevalent condition with devastating personal and public health consequences that often first manifests during adolescence. Though extensively studied, the pathogenesis of depression remains poorly understood, and efforts to stratify risks and identify optimal interventions have proceeded slowly. A major impediment has been the reliance on an all-or-nothing categorical diagnostic scheme based solely on whether a patient endorses an arbitrary number of common symptoms for a sufficiently long period. This approach masks the well-documented heterogeneity of depression, a disorder that is highly variable in presentation, severity, and course between individuals and is frequently comorbid with other psychiatric conditions. In this targeted review, we outline the limitations of traditional diagnosis-based research and instead advocate an alternative approach centered around symptoms as unique dimensions of clinical dysfunction that span across disorders and more closely reflect underlying neurobiological abnormalities. In particular, we highlight anhedonia—the reduced ability to anticipate and experience pleasure—as a specific, quantifiable index of reward dysfunction and an ideal candidate for dimensional investigation. Anhedonia is a core symptom of depression but also a salient feature of numerous other conditions, and its severity varies widely within clinical and even healthy populations. Similarly, reward dysfunction is a hallmark of depression but is evident across many psychiatric conditions. Reward function is especially relevant in adolescence, a period characterized by exaggerated reward-seeking behaviors and rapid maturation of neural reward circuitry. We detail extensive work by our research group and others to investigate the neural and systemic factors contributing to reward dysfunction in youth, including our cumulative findings using multiple neuroimaging and immunological measures to study depressed adolescents but also trans-diagnostic cohorts with diverse psychiatric symptoms. We describe convergent evidence that reward dysfunction: (a) predicts worse clinical outcomes, (b) is associated with functional and chemical abnormalities within and beyond the neural reward circuitry, (c) is linked to elevated peripheral levels of inflammatory biomarkers, and (d) manifests early in the course of illness. Emphasis is placed on high-resolution neuroimaging techniques, comprehensive immunological assays, and data-driven analyses to fully capture and characterize the complex, interconnected nature of these systems and their contributions to adolescent reward dysfunction.&lt;/jats:p&gt