FEMA: Fast and efficient mixed-effects algorithm for large sample whole-brain imaging data.

The linear mixed-effects model (LME) is a versatile approach to account for dependence among observations. Many large-scale neuroimaging datasets with complex designs have increased the need for LME; however LME has seldom been used in whole-brain imaging analyses due to its heavy computational requirements. In this paper, we introduce a fast and efficient mixed-effects algorithm (FEMA) that makes whole-brain vertex-wise, voxel-wise, and connectome-wide LME analyses in large samples possible. We validate FEMA with extensive simulations, showing that the estimates of the fixed effects are equivalent to standard maximum likelihood estimates but obtained with orders of magnitude improvement in computational speed. We demonstrate the applicability of FEMA by studying the cross-sectional and longitudinal effects of age on region-of-interest level and vertex-wise cortical thickness, as well as connectome-wide functional connectivity values derived from resting state functional MRI, using longitudinal imaging data from the Adolescent Brain Cognitive DevelopmentSM Study release 4.0. Our analyses reveal distinct spatial patterns for the annualized changes in vertex-wise cortical thickness and connectome-wide connectivity values in early adolescence, highlighting a critical time of brain maturation. The simulations and application to real data show that FEMA enables advanced investigation of the relationships between large numbers of neuroimaging metrics and variables of interest while considering complex study designs, including repeated measures and family structures, in a fast and efficient manner. The source code for FEMA is available via: https://github.com/cmig-research-group/cmig_tools/.

Heritability Estimation of Cognitive Phenotypes in the ABCD Study® Using Mixed Models.

Twin and family studies have historically aimed to partition phenotypic variance into components corresponding to additive genetic effects (A), common environment (C), and unique environment (E). Here we present the ACE Model and several extensions in the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), employed using the new Fast Efficient Mixed Effects Analysis (FEMA) package. In the twin sub-sample (n = 924; 462 twin pairs), heritability estimates were similar to those reported by prior studies for height (twin heritability = 0.86) and cognition (twin heritability between 0.00 and 0.61), respectively. Incorporating SNP-derived genetic relatedness and using the full ABCD Study® sample (n = 9,742) led to narrower confidence intervals for all parameter estimates. By leveraging the sparse clustering method used by FEMA to handle genetic relatedness only for participants within families, we were able to take advantage of the diverse distribution of genetic relatedness within the ABCD Study® sample.

Multi-ancestry phenome-wide association of complement component 4 variation with psychiatric and brain phenotypes in youth.

BACKGROUND: Increased expression of the complement component 4A (C4A) gene is associated with a greater lifetime risk of schizophrenia. In the brain, C4A is involved in synaptic pruning; yet, it remains unclear the extent to which upregulation of C4A alters brain development or is associated with the risk for psychotic symptoms in childhood. Here, we perform a multi-ancestry phenome-wide association study in 7789 children aged 9-12 years to examine the relationship between genetically regulated expression (GREx) of C4A, childhood brain structure, cognition, and psychiatric symptoms. RESULTS: While C4A GREx is not related to childhood psychotic experiences, cognition, or global measures of brain structure, it is associated with a localized reduction in regional surface area (SA) of the entorhinal cortex. Furthermore, we show that reduced entorhinal cortex SA at 9-10 years predicts a greater number and severity of psychosis-like events at 1-year and 2-year follow-up time points. We also demonstrate that the effects of C4A on the entorhinal cortex are independent of genome-wide polygenic risk for schizophrenia. CONCLUSIONS: Our results suggest neurodevelopmental effects of C4A on childhood medial temporal lobe structure, which may serve as a biomarker for schizophrenia risk prior to symptom onset.

Pharmacologic treatment of delirium symptoms: A systematic review.

OBJECTIVE: We conducted an updated, comprehensive, and contemporary systematic review to examine the efficacy of existing pharmacologic agents employed for management of delirium symptoms among hospitalized adults. METHODS: Searches of PubMed, Scopus, Embase, and Cochrane Library databases from inception to May 2021 were performed to identify studies investigating efficacy of pharmacologic agents for management of delirium. RESULTS: Of 11,424 articles obtained from searches, a total of 33 articles (N = 3030 participants) of randomized or non-randomized trials, in which pharmacologic treatment was compared to active comparator, placebo, or no treatment, met all criteria and were included in this review. Medications used for management of delirium symptoms included antipsychotic medications (N = 27), alpha-2 agonists (N = 5), benzodiazepines (N = 2), antidepressants (n = 1), acetylcholinesterase inhibitors (N = 2), melatonin (N = 2), opioids (N = 1), and antiemetics (N = 2). Despite somewhat mixed findings and a relative lack of high-quality trials, it appears that antipsychotic medications (e.g., haloperidol, olanzapine, risperidone, or quetiapine) and dexmedetomidine have the potential to improve delirium outcomes. CONCLUSIONS: Pharmacologic agents can reduce delirium symptoms (e.g., agitation) in some hospitalized patients. Additional double-blinded, randomized, placebo-controlled clinical trials are critically needed to investigate the efficacy of pharmacologic agents for diverse hospitalized populations (e.g., post-surgical patients, patients at the end-of-life, or in intensive care units).

Implementation of an antimicrobial stewardship programme in three regional hospitals in the south-east of Liberia: lessons learned.

Background: Antimicrobial stewardship (AMS) programmes can improve the use of antimicrobial agents. However, there is limited experience in the implementation of such programmes in low- and middle-income countries (LMICs). Objectives: To assess the effect of AMS measures in south-east Liberia on the quality of antimicrobial use in three regional hospitals. Methods: A bundle of three measures (local treatment guideline, training and regular AMS ward rounds) was implemented and quality indicators of antimicrobial use (i.e. correct compounds, dosage and duration) were assessed in a case series before and after AMS ward rounds. Primary endpoints were (i) adherence to the local treatment guideline; (ii) completeness of the microbiological diagnostics (according to the treatment guideline); and (iii) clinical outcome. The secondary endpoint was reduction in ceftriaxone use. Results: The majority of patients had skin and soft tissue infections (n = 108) followed by surgical site infections (n = 72), pneumonia (n = 64), urinary tract infection (n = 48) and meningitis (n = 18). After the AMS ward rounds, adherence to the local guideline improved for the selection of antimicrobial agents (from 34.5% to 61.0%, P < 0.0005), dosage (from 15.2% to 36.5%, P < 0.0005) and duration (from 13.2% to 31.0%, P < 0.0005). In total, 79.7% of patients (247/310) had samples sent for microbiological analysis. Overall, 92.3% of patients improved on Day 3 (286/310). The proportion of patients receiving ceftriaxone was significantly reduced after the AMS ward rounds from 51.3% to 14.2% (P < 0.0005). Conclusions: AMS measures can improve the quality of antimicrobial use in LMICs. However, long-term engagement is necessary to make AMS programmes in LMICs sustainable.

Emotional changes following discrimination induction in gender- and sexuality-diverse adolescents.

Sexual and gender minority (SGM)-identifying adolescents are particularly vulnerable to negative psychological outcomes, including engagement in nonsuicidal self-injury (NSSI). However, little is known about why these relationships exist. We used experimental methods to test the psychological mediation framework in an online sample of 328 adolescents who reported female sex at birth and a range of sexual and gender identities. Participants reported on depressive symptoms, self-criticism (both self-report and implicit), NSSI, and discrimination. They also completed a discrimination-based mood induction to test emotional reactivity. At baseline, SGM participants reported higher levels of implicit and self-reported self-criticism, depressive symptoms, discrimination, and higher rates of NSSI compared with cisgender, heterosexual participants (ps < .03). Following the discrimination induction, SGM-identifying participants exhibited larger emotional reactivity compared with cisgender heterosexual participants, as measured by change in negative mood, F(1, 326) = 7.33, p = .01, ηp2 = .02, and state self-criticism, F(1, 326) = 4.67, p = .03, ηp2 = .014, but not implicit affect toward the self. This effect was associated with baseline depressive symptoms, self-criticism, NSSI history, and discrimination. Post hoc analyses revealed that participants who tended to reframe experiences of discrimination as opportunities for growth exhibited attenuated emotional reactivity to the induction; findings remained significant after adjusting for SGM status and event severity (ps < .001). Results indicate that adolescents identifying as SGM may experience elevated psychological distress compared with their cisgender heterosexual peers and that stigma-related stressors may increase emotion dysregulation and maladaptive cognitive styles, paralleling previously proposed psychological mediation models. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Online Methods in Adolescent Self-Injury Research: Challenges and Recommendations.

Online methods hold promise as effective research tools for adolescent psychopathology research. Such methods may be the most effective way to reach large, representative samples of adolescents and harder-to-reach populations. They also may increase adolescent disclosure of risky behaviors, reduce recruitment costs, and increase the cost and time efficiency of recruitment. Despite these advantages, researchers may be concerned about including measures assessing risky behaviors, like suicidal thoughts and behaviors and nonsuicidal self-injury, in online studies of youth. In addition, parental consent in online studies is impractical and difficult to obtain. Concerns also include potential iatrogenic effects, sample bias, and data quality issues. This review discusses the benefits and challenges for online adolescent self-injury research, proposes strategies to overcome barriers, and provides examples and recommendations for future research.

Pre-enlistment Anger Attacks and Postenlistment Mental Disorders and Suicidality Among US Army Soldiers.

Importance: Anger is linked to adverse outcomes in military populations; however, whether pre-enlistment anger attacks are associated with postenlistment mental disorders and suicidality is unknown. Objective: To explore the associations of pre-enlistment anger attacks with postenlistment mental health. Design, Setting, and Participants: In this observational cohort study, the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) New Soldier Study (NSS) surveyed soldiers entering basic training from April 2011 to November 2012, with a subsample recruited for wave 1 of the STARRS Longitudinal Study (STARRS-LS) (conducted September 2016 to April 2018). Participants were recruited from 3 US Army installations for the NSS survey. Those who were subsequently contacted for STARRS-LS completed the follow-up survey via web or telephone. Prospective analyses were based on a weighted NSS subsample included in wave 1 of STARRS-LS. Data were analyzed from May 22, 2020, to March 17, 2021. Exposures: History of anger attacks at baseline (NSS). Survey responses were used to classify new soldiers as having nonimpairing anger attacks (>2 attacks without interference in work or personal life), impairing anger attacks (>2 attacks with interference in work or personal life), or no significant history of anger attacks. Main Outcomes and Measures: Baseline analyses examined sociodemographic and clinical correlates of a history of anger attacks. Prospective logistic regression models estimated associations of baseline history of anger attacks with new onset and persistence of posttraumatic stress disorder, major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder, mania/hypomania, substance use disorder, suicidal ideation, and suicide attempt at wave 1 of STARRS-LS. Results: Of the 38 507 baseline participants (83.0% male and 17.0% female; mean [SD] age, 20.97 [3.57] years), 6216 were selected for and completed wave 1 of the STARRS-LS. Baseline prevalence (SE) of nonimpairing and impairing anger attacks was 8.83% (0.16%) and 5.75% (0.15%), respectively. Prospective models showed that impairing anger attacks were associated with new onset of MDD (adjusted odds ratio [AOR], 1.98; 95% CI, 1.31-2.99), GAD (AOR, 2.39; 95% CI, 1.66-3.45), panic disorder (AOR, 2.02; 95% CI, 1.34-3.05), and suicidal ideation (AOR, 2.11; 95% CI, 1.45-3.07). When baseline psychiatric comorbidity was controlled for, impairing attacks remained associated with onset of GAD (AOR, 1.75; 95% CI, 1.19-2.58) and suicidal ideation (AOR, 1.62; 95% CI, 1.09-2.42). Anger attacks were not significantly associated with persistence of pre-enlistment mental disorders. Conclusions and Relevance: The findings of this study suggest that a pre-enlistment history of impairing anger attacks may be associated with elevated risk of developing GAD, MDD, and suicidality after enlistment. Detection of impairing anger attacks could aid in assessing psychiatric risk in new soldiers.

Recurrent versus new-onset depressive symptoms: Relationships with biomarkers of cardiovascular health following acute coronary syndrome.

OBJECTIVE: New-onset depressive symptoms commonly arise among persons without a history of major depressive disorder (MDD) in the setting of acute medical illness. Although depressive symptoms in general are associated with alterations in prognostic biomarkers following acute coronary syndrome (ACS), the nature of specifically new-onset depressive symptoms is less well-characterized. It is unclear whether such symptoms neurobiologically resemble recurrent symptoms of MDD or instead represent a distinct condition. In this exploratory analysis, we aimed to examine the effects of prior MDD history on the relationships between post-ACS depressive symptoms and cardiovascular biomarkers. METHODS: One-hundred sixty-four participants attended study visits 2 weeks and 6 months after ACS to complete self-report measures and provide biomarker samples. MDD history was identified by a psychiatrist through systematic electronic medical record review. Generalized estimating equations were performed to examine the moderating effects of MDD history on concurrent relationships between depressive symptoms and several biomarkers (endothelin-1, soluble intercellular adhesion molecule-1, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha). RESULTS: Twenty percent (n = 33) of participants had a history of MDD. Depressive symptoms were more strongly associated with levels of endothelin-1 in patients with prior MDD compared to those without (B = 0.024, 95% CI [0.005, 0.043], p = .012), adjusting for age, sex, medical factors, and anxiety. MDD history did not moderate relationships between depressive symptoms and other biomarkers. CONCLUSION: Recurrent post-ACS depressive symptoms are more strongly associated with elevated endothelin-1 levels than new-onset symptoms. Further work is needed to clarify the mechanism and clinical implications of this relationship.

Longitudinal predictors of self-injurious thoughts and behaviors in sexual and gender minority adolescents.

Sexual and gender minority (SGM) populations are at increased risk for several negative psychological outcomes, including self-injury. Although correlates of self-injurious thoughts and behaviors (SITBs) have been identified, it is unclear which factors are prospective predictors of SITB engagement in SGM youth. The current study investigated an online sample of 252 SGM adolescents over a 6-month period. Participants reported attitudes based on SGM identity, depression, self-criticism, body image, family support and family strain, friend NSSI engagement, and experiences of everyday discrimination. Lasso and elastic net regularized logistic regressions were used to examine which baseline variables were associated with SITB engagement at follow-up. Models resulted in excellent predictive accuracy of nonsuicidal self-injury and suicidal ideation (mean Area Under the Receiving Operating Characteristics Curve [AUC] of 0.90 and 0.91), good predictive accuracy for suicide plans (mean AUC = 0.85), and fair predictive accuracy for suicidal behaviors (mean AUC = 0.78). Several variables emerged as prospectively related to SITB risk, with varied associations across different SITBs. Results suggest that minority-specific factors may predict SITBs in SGM adolescents. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Text Message Interventions for Physical Activity: A Systematic Review and Meta-Analysis.

CONTEXT: Despite clear health benefits, many individuals fail to achieve the recommended levels of physical activity. Text message interventions to promote physical activity hold promise owing to the ubiquity of cell phones and the low expense of text message delivery. EVIDENCE ACQUISITION: A systematic review and meta-analysis were performed to examine the impact of text message interventions on physical activity. Searches of PubMed, PsycINFO, Scopus, Cochrane, and ClinicalTrials.gov databases from inception to December 2017 were performed to identify studies investigating one-way text message interventionss to promote physical activity. A subset of RCTs, including an objective (accelerometer-based) physical activity outcome, were included in random-effects meta-analyses in 2018. EVIDENCE SYNTHESIS: The systematic search revealed 944 articles. Of these, 59 were included in the systematic review (12 1-arm trials and 47 controlled trials; n=8,742; mean age, 42.2 years; 56.2% female). In meta-analyses of 13 studies (n=1,346), text message interventionss led to significantly greater objectively measured postintervention steps/day (Cohen's d=0.38, 95% CI=0.19, 0.58, n=10 studies). Analysis of postintervention moderate-to-vigorous physical activity found a similar but not statistically significant effect (Cohen's d=0.31, 95% CI= -0.01, 0.63, n=5 studies). Interventions with more components, tailored content, and interventions in medical populations led to nonsignificantly larger effect sizes compared with text message interventions without these features. CONCLUSIONS: Text message interventions lead to higher objectively measured postintervention physical activity compared with control groups. More extensive, well-controlled studies are needed to examine this relationship further and identify characteristics of effective text message interventions.

Understanding Contextual Spillover: Using Identity Process Theory as a Lens for Analyzing Behavioral Responses to a Workplace Dietary Choice Intervention.

Spillover occurs when one environmentally sustainable behavior leads to another, often initiated by a behavior change intervention. A number of studies have investigated positive and negative spillover effects, but empirical evidence is mixed, showing evidence for both positive and negative spillover effects, and lack of spillover altogether. Environmental identity has been identified as an influential factor for spillover effects. Building on identity process theory the current framework proposes that positive, negative, and a lack of spillover are determined by perceived threat of initial behavior and identity process mechanisms evaluating the behavior. It is proposed, that an environmental behavior change intervention may threaten one's existing identities, leading to either (a) integration, (b) compartmentalization, or (c) conflict between one's environmental identity and non-environmental identities. Initial evidence for the proposed framework is based on a field intervention which included a meat reduction programme in a canteen of a medium size private sector company. Semi-structured interviews and an explorative visualization method that aimed at assessing identity change were implemented with thirteen employees (i.e., intervention participants) before and after the intervention. The qualitative data was analyzed by using thematic analysis via NVivo12. Results of the visualization task and interview method provided initial evidence of direct and indirect positive contextual spillover effects, with comparatively less evidence a lack of spillover and a relative absence of reported negative spillover. This paper provides a novel theoretical approach, centered on identity process theory to enhance understanding of positive spillover, negative spillover, and the lack of spillover.

Does nonsuicidal self-injury prospectively predict change in depression and self-criticism?

Few studies have investigated nonsuicidal self-injury (NSSI) as a predictor of outcomes other than suicidal self-injury, severely limiting our understanding of this behavior's full range of consequences. Three independent studies were used to examine the prospective association between NSSI and two outcomes: depressive symptoms and self-criticism. Data were collected from samples of (1) adults with past-month NSSI, (2) adults with lifetime NSSI, and (3) adults with past-year NSSI. Studies included one-month and six-month follow-up periods. Results were tested in an internal meta-analysis. Results suggested that NSSI did not prospectively predict changes in self-criticism. No changes in depressive symptoms were seen over shorter follow-up periods; however, NSSI predicted increases in depressive symptoms at six-month follow-up in one sample. The internal meta-analysis indicated a null relationship between NSSI and prospective internalizing symptoms. Future research should replicate these findings and examine a broader range of outcomes of NSSI to better understand its complex relationship to psychopathology.

Self-Injurious Thoughts and Behaviors May Be More Common and Severe Among People Identifying as a Sexual Minority.

Research indicates that people who identify as a sexual minority are at higher risk of numerous negative outcomes, including self-injurious thoughts and behaviors (SITBs). The minority stress model proposes that people identifying as a sexual minority are at higher risk of these behaviors due to sexual orientation-specific stressors-however, it does not clarify whether SITBs will be more severe among these individuals. The present study tested whether SITBs are more common and more severe among people identifying as a sexual minority using several metrics, including frequency of SITB engagement, age of onset of SITB, desire to discontinue SITB engagement, and likelihood of future SITBs. Four independent research samples were used to test this model. Results were then combined and tested in an internal meta-analysis. Findings converge to indicate a longer and more severe course of SITB engagement among people identifying as a sexual minority. Future research is needed to replicate these findings and to advance the understanding of why this imbalance in risk and severity might exist, and how it can be prevented.

Positive Value of a Women's Junior Faculty Mentoring Program: A Mentor-Mentee Analysis.

BACKGROUND: Recently appointed women faculty in academic medicine face many challenges during their careers and can become overwhelmed managing their multiple faculty roles as teacher, scholar, and clinician, in addition to their roles in personal life. Although a mentor can be invaluable in assisting a woman junior faculty member to adjust to faculty life and providing critical career guidance, not all medical institutions have faculty mentoring programs. We created a mentoring program specifically for our women junior faculty to address this issue at our own institution. MATERIALS AND METHODS: To assess the value of this program, we conducted a novel mentor-mentee paired-data analysis of annual surveys collected from 2010 to 2015. Of the 470 responses received, 83 were from unique mentees and 61 from unique mentors. RESULTS: Career development, research, and promotion were the top topics discussed among the mentoring pairs, followed by discussions of institutional resources and administration/service. There was high congruency among the mentoring pairs that they thought these discussions, as well as other conversations about mentee professional development and well-being, had been helpful. However in some instances, mentors felt they had not been helpful to their mentee, whereas their mentees felt otherwise; this finding speaks to the value and importance of mentees providing positive feedback to their mentors. Overall, both mentees and mentors thought that the mentees had significantly benefited from the mentorship. Unexpected outcomes of these relationships included promotion, grant applications/awards, articles, presentations, and professional memberships. The use of a Mentee Needs Assessment Form to individualize the mentoring relationship for each mentee may explain the high overall satisfaction and participant recommendations of the program. CONCLUSIONS: Our findings demonstrate the value in establishing mentoring programs specifically for women faculty, especially in environments in which other mentoring opportunities do not exist.

2016 AAHA Oncology Guidelines for Dogs and Cats.

All companion animal practices will be presented with oncology cases on a regular basis, making diagnosis and treatment of cancer an essential part of comprehensive primary care. Because each oncology case is medically unique, these guidelines recommend a patient-specific approach consisting of the following components: diagnosis, staging, therapeutic intervention, provisions for patient and personnel safety in handling chemotherapy agents, referral to an oncology specialty practice when appropriate, and a strong emphasis on client support. Determination of tumor type by histologic examination of a biopsy sample should be the basis for all subsequent steps in oncology case management. Diagnostic staging determines the extent of local disease and presence or absence of regional or distant metastasis. The choice of therapeutic modalities is based on tumor type, histologic grade, and stage, and may include surgery, radiation therapy, chemotherapy, immunotherapy, and adjunctive therapies, such as nutritional support and pain management. These guidelines discuss the strict safety precautions that should be observed in handling chemotherapy agents, which are now commonly used in veterinary oncology. Because cancer is often a disease of older pets, the time of life when the pet-owner relationship is usually strongest, a satisfying outcome for all parties involved is highly dependent on good communication between the entire healthcare team and the client, particularly when death or euthanasia of the patient is being considered. These guidelines include comprehensive tables of common canine and feline cancers as a resource for case management and a sample case history.

Periodontitis prevalence and serum antibody reactivity to periodontal bacteria in primary Sjögren's syndrome: a pilot study.

AIMS: The aims of this study were as follows: (i) To assess the prevalence of periodontitis among patients with primary Sjögren's syndrome (pSS) and comparator groups of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). (ii) To perform a pilot study to compare serum antibody responses to 10 oral/periodontal bacteria in these patient groups and a historical comparator group of patients with periodontitis. MATERIALS AND METHODS: Standard clinical periodontal assessments were performed on 39 pSS, 36 RA and 23 OA patients and "In-house" antibody ELISAs for serum antibodies against 10 oral/periodontal bacteria were performed in these groups. RESULTS: Forty-six percent of the pSS group, 64% of the RA group and 48% of the OA group had moderate/severe periodontitis. These frequencies did not reach statistical significance between groups. Raised antibody levels to Prevotella denticola were found in the pSS, RA and periodontitis groups compared to the OA group. Significant between group differences were seen for Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Campylobacter showae. None of these differences were specifically associated with pSS. CONCLUSION: This study showed no increase in periodontitis in pSS patients. Although the P. denticola data are of interest, identifying bacterial triggering factors for pSS will likely require alternative strategies including modern techniques such as microbiome analysis.