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Eosinophils are granular leukocytes that play a role in mediating inflammatory responses linked to infection and allergic disease. Their activation during an immune response triggers spatial reorganization and eventual cargo release from intracellular granules. Understanding this process is important in diagnosing eosinophilic disorders and in assessing treatment efficacy; however, current protocols are limited to simply quantifying the number of eosinophils within a blood sample. Given that high optical absorption and scattering by the granular structure of these cells lead to marked image features, the physical changes that occur during activation should be trackable using image analysis. Here, we present a study in which imaging flow cytometry is used to quantify eosinophil activation state, based on the extraction of 85 distinct spatial features from dark‐field images formed by light scattered orthogonally to the illuminating beam. We apply diffusion mapping, a time inference method that orders cells on a trajectory based on similar image features. Analysis of exogenous cell activation using eotaxin and endogenous activation in donor samples with elevated eosinophil counts shows that cell position along the diffusion‐path line correlates with activation level (99% confidence level). Thus, the diffusion mapping provides an activation metric for each cell. Assessment of activated and control populations using both this spatial image‐based, activation score and the integrated side‐scatter intensity shows an improved Fisher discriminant ratio r d = 0.7 for the multivariate technique compared with an r d = 0.47 for the traditional whole‐cell scatter metric. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

White blood cell (WBC) differential counting is an established clinical routine to assess patient immune system status. Fluorescent markers and a flow cytometer are required for the current state‐of‐the‐art method for determining WBC differential counts. However, this process requires several sample preparation steps and may adversely disturb the cells. We present a novel label‐free approach using an imaging flow cytometer and machine learning algorithms, where live, unstained WBCs were classified. It achieved an average F1‐score of 97% and two subtypes of WBCs, B and T lymphocytes, were distinguished from each other with an average F1‐score of 78%, a task previously considered impossible for unlabeled samples. We provide an open‐source workflow to carry out the procedure. We validated the WBC analysis with unstained samples from 85 donors. The presented method enables robust and highly accurate identification of WBCs, minimizing the disturbance to the cells and leaving marker channels free to answer other biological questions. It also opens the door to employing machine learning for liquid biopsy, here, using the rich information in cell morphology for a wide range of diagnostics of primary blood. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Tourette syndrome (TS) is a neurodevelopmental disorder that is characterized by vocal and motor tics. Children with TS often also exhibit disruptive behaviors including sudden anger outbursts accompanied by verbal and physical aggression. This case study presents cognitive behavioral therapy (CBT) treatment of anger and aggression in a 9-year-old girl with TS, co-occurring generalized anxiety disorder (GAD), and oppositional defiant disorder (ODD). At initial assessment, tics were well-managed and disruptive behavior concerns, including near-daily tantrums lasting 20 min to 1 hr, were primary clinical concerns. The child and her mother received 12 weekly sessions of CBT for anger and aggression, with select supplements and modifications that related to the context of TS. Posttreatment assessment indicated a significant decrease in noncompliance, anger outbursts, and aggressive behavior. CBT for anger and aggression can be a useful treatment for the disruptive behaviors that often co-occur with TS.

Disruptive mood dysregulation disorder (DMDD) is a relatively new diagnosis in the field of childhood onset disorders. Characterized by both behavior and mood disruption, DMDD is a purportedly unique clinical presentation with few relevant treatment studies to date. The current case study presents the application of cognitive-behavioral therapy (CBT) for anger and aggression in a 9-year-old girl with DMDD, co-occurring attention deficit hyperactivity disorder (ADHD), and a history of unspecified anxiety disorder. At the time of intake evaluation, she demonstrated three to four temper outbursts and two to three episodes of aggressive behavior per week, in addition to prolonged displays of non-episodic irritability lasting hours or days at a time. A total of 12 CBT sessions were conducted over 12 weeks and 5 follow-up booster sessions were completed over a subsequent 3-month period. Irritability-related material was specially designed to target the DMDD clinical presentation. Post-treatment and 3-month follow-up assessments, including independent evaluation, demonstrated significant decreases in the target symptoms of anger, aggression, and irritability. Although the complexities of diagnosing and treating DMDD warrant extensive research inquiry, the current case study suggests CBT for anger and aggression as a viable treatment for affected youth.

Anger, irritability, and aggression are among the most common reasons for child mental health referrals. This review is focused on two forms of behavioral interventions for these behavioral problems: Parent management training (PMT) and cognitive-behavioral therapy (CBT).First, we provide an overview of anger/irritability and aggression as the treatment targets of behavioral interventions, followed by a discussion of the general principles and techniques of these treatment modalities. Then we discuss our current work concerning the transdiagnostic approach to CBT for anger, irritability, and aggression.PMT is aimed at improving aversive patterns of family interactions that engender children's disruptive behavior. CBT targets deficits in emotion regulation and social problem-solving that are associated with aggressive behavior. Both forms of treatment have received extensive support in randomized controlled trials. Given that anger/irritability and aggressive behavior are common in children with a variety of psychiatric diagnoses, a transdiagnostic approach to CBT for anger and aggression is described in detail.PMT and CBT have been well studied in randomized controlled trials in children with disruptive behavior disorders, and studies of transdiagnostic approaches to CBT for anger and aggression are currently underway. More work is needed to develop treatments for other types of aggressive behavior (e.g., relational aggression) that have been relatively neglected in clinical research. The role of callous-unemotional traits in response to behavioral interventions and treatment of irritability in children with anxiety and mood disorders also warrants further investigation.