Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images

Purpose

Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images.

Procedures

Data were acquired from three previously reported clinical studies with [⁸⁹Zr]antiCD20 (74 MBq, n?=?7), [⁸⁹Zr]antiEGFR (37 MBq, n?=?7), and [⁸⁹Zr]antiCD44 (37 MBq, n?=?13), with imaging obtained 1 to 6 days post injection (D0–D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50 % of the original injected dose (e.g., 37 MBq_74inj).Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images.

Results

The RC for the combined manually delineated organs for [⁸⁹Zr] antiCD20 (37 MBq_74inj) increased from D0 to D6 and was less than 6 % at all time points. Blood pool and bone marrow had higher RC, up to 43 % for 37 MBq_74inj at D6. For tumor, the RC was up to 42 % for [⁸⁹Zr]antiCD20 (37 MBq_74inj). For [⁸⁹Zr]antiCD20, (18 MBq_74inj), [⁸⁹Zr]antiEGFR (18 MBq_37inj), and [⁸⁹Zr]antiCD44 (18 MBq_37inj), measurement variability was independent of the investigated antibody.

Conclusions

Based on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37 MBq) around 6 % for manually delineated organs combined, increasing up to 43 % at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42 %.

     

A Transdiagnostic Minority Stress Treatment Approach for Gay and Bisexual Men’s Syndemic Health Conditions

Developing and deploying separate treatments for separate conditions seems ill-suited to intervening upon the co-occurring, and possibly functionally similar, psychosocial conditions facing gay and bisexual men. This article argues for the need to create transdiagnostic interventions that reduce multiple syndemic conditions facing gay and bisexual men at the level of their shared source in minority stress pathways. This article first reviews psychosocial syndemic conditions affecting gay and bisexual men, then suggests pathways that might link minority stress to psychosocial syndemics based on recent advancements in emotion science, psychiatric nosology, and cognitive-affective neuroscience, and finally suggests cross-cutting psychosocial treatment principles to reduce minority stress?syndemic pathways among gay and bisexual men. Because minority stress serves as a common basis of all psychosocial syndemic conditions reviewed here, locating the pathways through which minority stress generates psychosocial syndemics and employing overarching treatment principles capable of simultaneously alleviating these pathways will ultimately create a transdiagnostic approach to improving gay and bisexual men’s health. Clinical research and training approaches are suggested to further validate the pathways suggested here, establish the efficacy of treatment approaches tied to those pathways, and generate effective methods for disseminating a transdiagnostic minority stress treatment approach for gay and bisexual men’s psychosocial syndemic health.     

Assessing the Role of Masculinity in the Transmission of HIV: A Systematic Review to Inform HIV Risk Reduction Counseling Interventions for Men Who Have Sex with Men

HIV affects over 1.2 million people in the United States; a substantial number are men who have sex with men (MSM). Despite an abundance of literature evaluating numerous social/structural and individual risk factors associated with HIV for this population, relatively little is known regarding the individual-level role of masculinity in community-level HIV transmission risk. To address this gap, the current analysis systematically reviewed the masculinity and HIV literature for MSM. The findings of 31 sources were included. Seven themes were identified: (1) number of partners, (2) attitudes toward condoms, (3) drug use, (4) sexual positioning, (5) condom decision-making, (6) attitudes toward testing, and (7) treatment compliance. These factors, representing the enactment of masculine norms, potentiate the spread of HIV. The current article aligns these factors into a masculinity model of community HIV transmission. Opportunities for counseling interventions include identifying how masculinity informs a client’s cognitions, emotions, and behaviors as well as adapting gender-transformative interventions to help create new conceptualizations of masculinity for MSM clients. This approach could reduce community-level HIV incidence.     

Reflections on New York City’s 1947 Smallpox Vaccination Program and Its 1976 Swine Influenza Immunization Program

In 1947, a smallpox outbreak occurred in New York City with a total of twelve cases and two deaths. In order to contain this outbreak, the New York City Department of Health launched a mass immunization campaign that over a period of some 60 days vaccinated 6.35 million people. This article examines in detail the epidemiology of this outbreak and the measures employed to contain it. In 1976, a swine influenza strain was isolated among a few recruits at a US Army training camp at Fort Dix, New Jersey. It was concluded at the time that this virus possibly represented a re-appearance of the 1918 influenza pandemic influenza strain. As a result, a mass national immunization program was launched by the federal government. From its inception, the program encountered a myriad of challenges ranging from doubts that it was even necessary to the development of Guillain-Barré paralysis among some vaccine recipients. This paper examines the planning for and implementation of the swine flu immunization program in New York City. It also compares it to the smallpox vaccination program of 1947. Despite equivalent financial and personnel resources, leadership and organizational skills, the 1976 program only immunized approximately a tenth of the number of New York City residents vaccinated in 1947. The reasons for these marked differences in outcomes are discussed in detail.     

Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation

Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7 -week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3–72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids.     

Prospective Relation Between Peer Victimization and Suicidal Ideation: Potential Cognitive Mediators

The current study combines models about the effects of peer victimization on negative self-cognitions with models about the effects of negative cognitions on suicidal ideation. In a two-wave longitudinal investigation of high schoolers (N?=?192) and college students (N?=?142), the study examined perceived burdensomeness, thwarted belongingness, and hopelessness as mediators of the prospective relation between peer victimization and suicidal ideation. Path analyses yielded three findings: (a) peer victimization predicted perceived burdensomeness but not thwarted belongingness or hopelessness; (b) perceived burdensomeness, thwarted belongingness, and hopelessness each predicted suicidal ideation; and (c) perceived burdensomeness mediated part of the relation between peer victimization and suicidal ideation. These patterns were consistent across samples and did not differ significantly by gender. Results are consistent with aspects of all three original models and provide support for a new cognitive mediation model regarding the relation of peer victimization to suicidal ideation.     

Examining the Role of Repetitive Negative Thinking in Relations Between Positive and Negative Aspects of Self-compassion and Symptom Improvement During Intensive Treatment

Positive aspects of self-compassion (i.e., self-kindness and nonjudgmental acceptance of personal experiences) as well as negative aspects (i.e., high self-criticism and self-coldness) are strong predictors of anxiety, depression, worry, and quality of life. To date, however, relatively little is known about (a) how both aspects of self-compassion change during naturalistic treatment, (b) whether and how such changes relate to symptom improvement, and (c) which processes might explain the potential benefits of self-compassion. To address these gaps, the present study examined whether relations between changes in both aspects of self-compassion and treatment outcomes in a brief partial hospital setting for acute psychology could be explained by associated changes in repetitive negative thinking (RNT), an established maladaptive cognitive process involved in anxiety and depressive disorders. In a sample of 582 people receiving cognitive-behavioral (CBT) and dialectical behavior therapy over the course of 1–2 weeks, increases in positive aspects of self-compassion and decreases in negative aspects related to improvements in depression and anxiety. RNT mediated the relationship between decreases in negative aspects of self-compassion and improvements in anxiety and depression. However, a reverse model also showed that decreases in negative aspects of self-compassion could also explain relations between RNT and depressive symptom improvement only. These findings suggest that negative aspects of self-compassion and RNT may constitute important targets for treatment in acute settings. Future studies should investigate the impact of greater focus on self-compassion on RNT and symptom improvement using longitudinal experimental designs with multiple assessment points, examining causality and directionality.     

Group Cognitive Rehabilitation and Exposure/Sorting Therapy: A Pilot Program

While cognitive-behavioral therapy for hoarding disorder (HD) has resulted in significant reductions in symptoms, most individuals continue to have significant hoarding symptoms following treatment. This investigation sought to extend the literature on the behavioral treatments for hoarding by examining (1) group cognitive rehabilitation and exposure/sorting therapy (CREST) and (2) group exposure therapy (ET) for hoarding. Participants in both studies reported significant decreases in hoarding symptom severity from baseline to post-treatment on all primary outcome measures using mixed-effects linear regression models with the intent to treat sample. Participants who received group CREST reported statistically significant reductions in anxiety, depression, and overall severity at post-treatment, while participants who received group ET did not. Results provide preliminary evidence for both group CREST and group ET as effective treatments for hoarding disorder.     

The Brief State Rumination Inventory (BSRI): Validation and Psychometric Evaluation

Depressive rumination is an emotion regulation strategy that is considered a major risk factor for depression and other emotional disorders. While well-established measures of trait rumination are available, a psychometrically sound measure of state rumination is lacking. We report on the development and validation of a new self-report measure, the Brief State Rumination Inventory (BSRI), in both Dutch and English. In Study 1, we report the results of a multi-group confirmatory factor analysis across three independent samples (n?=?155; n?=?141; n?=?199). The analysis supported the unidimensionality and measurement invariance of the 8-item BSRI. We also examined its construct validity, showing that scores on the BSRI were positively related to measures of negative affect, trait rumination, and symptoms of depression and anxiety. Scores were negatively related to adaptive emotion regulation strategies and to positive affect. In Study 2 (n?=?60), we demonstrated the measure’s sensitivity to an experimental manipulation of rumination. Taken together, these findings suggest that the BSRI is a quick-to-administer, valid, and reliable measure of state rumination.     

Obsessive–Compulsive Disorder is Characterized by a Lack of Adaptive Coping Rather than an Excess of Maladaptive Coping

The present study aimed to elucidate the profile of coping in patients with obsessive–compulsive disorder (OCD) in order to discern whether the disorder is characterized by an excess of maladaptive coping skills and/or a lack of adaptive coping skills. Sixty individuals with OCD were compared with 110 individuals with depression and 1050 nonclinical controls on the Maladaptive and Adaptive Coping Styles Questionnaire (MAX). Psychopathology was assessed with the Obsessive–Compulsive Inventory-Revised (OCI-R), the Yale-Brown Obsessive–Compulsive Scale (Y-BOCS), and the Patient Health Questionnaire-9 for depression (PHQ-9). Individuals with OCD and depression displayed more maladaptive coping and avoidance as well as less adaptive coping than nonclinical controls. Importantly, adaptive coping was significantly lower in individuals with OCD than in those with depression at a medium effect size, whereas the clinical groups were indistinguishable on maladaptive coping and avoidance. Lack of adaptive coping was strongly correlated with resistance to symptoms and poor insight in OCD (Y-BOCS), even after controlling for depression. Lack of adaptive coping skills may represent a specific pathogenetic factor in OCD. Longitudinal studies need to clarify whether strengthening adaptive skills during childhood and adolescence may help to prevent the progression from subclinical to manifest OCD.