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OBJECTIVES/HYPOTHESIS: To understand the effect of the COVID-19 pandemic on the volume, quality, and impact of otolaryngology publications. STUDY DESIGN: Retrospective analysis. METHODS: Fifteen of the top peer-reviewed otolaryngology journals were queried on PubMed for COVID and non-COVID-related articles from April 1, 2020 to March 31, 2021 (pandemic period) and pre-COVID articles from the year prior. Information on total number of submissions and rate of acceptance were collected from seven top-ranked journals. RESULTS: Our PubMed query returned 759 COVID articles, 4,885 non-COVID articles, and 4,200 pre-COVID articles, corresponding to a 34% increase in otolaryngology publications during the pandemic period. Meta-analysis/reviews and miscellaneous publication types made up a larger portion of COVID publications than that of non-COVID and pre-COVID publications. Compared to pre-COVID articles, citations per article 120 days after publication and Altmetric Attention Score were higher in both COVID articles (citations/article: 2.75 ± 0.45, P < .001; Altmetric Attention Score: 2.05 ± 0.60, P = .001) and non-COVID articles (citations/article: 0.03 ± 0.01, P = .002; Altmetric Attention Score: 0.67 ± 0.28, P = .016). COVID manuscripts were associated with a 1.65 times higher acceptance rate compared to non-COVID articles (P < .001). CONCLUSIONS: COVID-19 was associated with an increase in volume, citations, and attention for both COVID and non-COVID articles compared to pre-COVID articles. However, COVID articles were associated with lower evidence levels than non-COVID and pre-COVID articles. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2021.

Background While effective treatments for posttraumatic stress disorder (PTSD) exist, many individuals, including military personnel and veterans fail to respond to them. Equine‐assisted therapy (EAT), a novel PTSD treatment, may complement existing PTSD interventions. This study employs longitudinal neuro‐imaging, including structural magnetic resonance imaging (sMRI), resting state‐fMRI (rs‐fMRI), and diffusion tensor imaging (DTI), to determine mechanisms and predictors of EAT outcomes for PTSD. Method Nineteen veterans with PTSD completed eight weekly group sessions of EAT undergoing multimodal MRI assessments before and after treatment. Clinical assessments were conducted at baseline, post‐treatment and at 3‐month follow‐up. Results At post‐treatment patients showed a significant increase in caudate functional connectivity (FC) and reduction in the gray matter density of the thalamus and the caudate. The increase of caudate FC was positively associated with clinical improvement seen immediately at post‐treatment and at 3‐month follow‐up. In addition, higher baseline caudate FC was associated with greater PTSD symptom reduction post‐treatment. Conclusions This exploratory study is the first to demonstrate that EAT can affect functional and structural changes in the brains of patients with PTSD. The findings suggest that EAT may target reward circuitry responsiveness and produce a caudate pruning effect from pre‐ to post‐treatment., This study employs longitudinal neuro‐imaging, including structural magnetic resonance imaging (sMRI), resting state‐fMRI (rs‐fMRI), and diffusion tensor imaging (DTI), to determine mechanisms and predictors of EAT outcomes for PTSD.

Surrogate markers of the host immune response are not currently included in AJCC staging for Merkel cell carcinoma (MCC), and have not been consistently associated with clinical outcomes. We performed an analysis of a large national database to investigate tumor infiltrating lymphocyte (TIL) grade as an independent predictor of overall survival (OS) for patients with MCC and to characterize the relationship between TIL grade and other clinical prognostic factors.The NCDB was queried for patients with resected, non-metastatic MCC with known TIL grade (absent, non-brisk and brisk). Multivariable Cox regression modeling was performed to define TIL grade as a predictor of OS adjusting for other relevant clinical factors. Multinomial, multivariable logistic regression was performed to characterize the relationship between TIL grade and other clinical prognostic factors. Multiple imputation was performed to account for missing data bias.Both brisk (HR 0.55, CI 0.36-0.83) and non-brisk (HR 0.77, CI 0.60-0.98) were associated with decreased adjusted hazard of death relative to absent TIL grade. Adverse clinical factors such as 1-3 positive lymph nodes, lymphovascular invasion (LVI) and immunosuppression were associated with increased likelihood of non-brisk TIL relative to absent TIL grade (Histopathologic TIL grade was independently predictive for OS in this large national cohort. Significant differences in the likelihood of non-brisk or brisk TIL relative to absent grade were present with regards to LVI, ECS and immune status. TIL grade may be a useful prognostic factor to consider in addition to more granular characterization of TIL morphology and immunophenotype.

Change-resistant behavior, such as rigid and selective food consumption, is a core symptom of autism that can have significant negative consequences for the child (Flygare Wallén et al., 2018; Levy et al., 2019). In the current study, we used a matching-law-based intervention (Fisher et al., 2019) to treat the change-resistant feeding behavior of 7 young children with autism. The feeder gave the participant a choice between a change-resistant and an alternative food during free- and asymmetrical-choice conditions. Alternative-food consumption increased for 2 participants during asymmetrical choice when the feeder provided a preferred item for consuming the alternative food and no programmed consequence for consuming the change-resistant food. Alternative-food consumption increased for the other 5 participants after the feeder exposed at least 1 food to single choice in which the feeder guided the participant to put the bite of alternative food in his or her mouth if he or she did not do so within 8 s of presentation. Effects of the single-choice contingencies maintained during reversals and generalized to other alternative foods the feeder did not expose to single choice. These results are important because participants consumed alternative foods even when their change-resistant foods were present, which is similar to typical mealtime contexts in which children have choices among foods.

Immunosuppressed (IS) patients are at increased risk for developing Merkel cell carcinoma (MCC) with worsened outcomes compared to immunocompetent (IC) patients. We sought to determine the effects of immune status on the efficacy of adjuvant RT regarding OS for patients with stage I, II or III (localized) MCC of the head and neck. The National Cancer Database was queried for patients with resected, localized MCC of the head and neck with known immune status. Kaplan–Meier methods were used to describe OS. Log-rank tests, multivariable Cox regression models and interaction effect testing were used to compare OS by subgroup categorized by patient and treatment factors including immune status and adjuvant RT receipt. A total of 892 (89.6%) IC and 104 (10.4%) IS patients with MCC of the head and neck were included. Adjuvant RT was associated with improved 3-year OS rate for both IS patients (49.4% vs. 35.5%, p = 0.0467) and stage I/II IC patients (72.4% vs. 62.9%, p = 0.0092). Adjuvant RT was associated with decreased hazard of death (HR 0.77, 95% CI 0.62–0.95). Interaction effect testing did not demonstrate a difference in the efficacy of adjuvant RT on OS between IC and IS status (p = 0.157). In this NCDB analysis, adjuvant RT was associated with decreased hazard of death for patients with localized MCC of the head and neck regardless of immune status and should be considered for both IS and IC patients.

Introduction Equine-assisted therapy (EAT) for post-traumatic stress disorder (PTSD) has attracted great interest despite lacking empirical support, a manual, and a standardized protocol. Our team of experts in EAT and PTSD developed an eight-session group EAT treatment protocol for PTSD (EAT-PTSD) and administered it to two pilot groups of military veterans to assess initial effects. Materials and Methods We describe the development of the treatment manual, which was used with two pilot groups of veterans. Protocol safety, feasibility, and acceptability were assessed by reported adverse events, treatment completion rates, and self-rated patient satisfaction. Preliminary data on PTSD, depressive, and anxiety symptoms and quality of life were collected pretreatment, midpoint, post-treatment, and at 3-month follow up. Results No adverse events were recorded. All patients completed treatment, reporting high satisfaction. Preliminary data showed decreases in clinician-assessed PTSD and depressive symptoms from pre to post-treatment and follow-up (medium to large effect sizes, d = .54–1.8), with similar trends across self-report measures (d = 0.72–1.6). In our pilot sample, treatment response and remission varied; all patients showed some benefit post-treatment, but gains did not persist at follow-up. Conclusions This article presents the first standardized EAT protocol. Highly preliminary results suggest our new manualized group EAT-PTSD appears safe, well-regarded, and well-attended, yielding short-term benefits in symptomatology and quality of life if unclear length of effect. Future research should test this alternative treatment for PTSD more rigorously.

The development of additive manufacturing in the 1980s led to a revolution in various metalcasting processes as early as the 1990s, including the use of polymer 3D printing for the manufacture of sand casting patterns. While additive manufacturing has entered many metalcasting processes, including both expendable and permanent mold processes, this paper specifically examines the sand casting process. ExOne’s development of binder jetting technology over the last 20 years has allowed designers in the sand casting field to directly 3D print sand molds for metalcasting. Use of binder jet additively manufactured sand molds allows for quicker turnaround time for testing prototypes, new gating designs, and for producing one-off parts. Additive manufacturing of sand molds for metalcasting may implement any of the same foundry sands as green sand processes, but uses a furan binder instead of the traditional mixture of bentonite clay and water. The use of a chemical binder had led to questions about the resulting dimensional capabilities and mechanical properties of the castings produced by the mold. This study investigated the dimensional tolerancing capabilities, surface finish, mechanical properties, microstructure, and defects present in identical castings made from both a traditional olivine green sand molding process and a binder jet additively manufactured silica sand molding process. It was concluded that binder jet additively manufactured sand molds are capable of either equal or better dimensional accuracy and tolerance capabilities than traditional olivine green sand molds. The olivine green sand parts had an average of approximately 1 μm better surface finish than the binder jet sand molds; however, it is likely that both the addition of sea coal to the green sand and the difference in final part color significantly affected this result. The mean hardness of the binder jet parts was 58.9 HBW with a standard deviation of 5.6 HBW, compared to the mean of the green sand parts of 47.7 HBW with a standard deviation of 7.2 HBW. The hardness findings were confirmed by the presence of a finer microstructure in the binder jet parts than the green sand parts. While both types of molds produced parts with defects, a greater variety of defects was evident in the olivine green sand molds. Porosity tended to move toward the surface of the olivine green sand parts, but was relatively evenly spread through the additively manufactured sand mold parts.

BACKGROUND Suicide is a leading cause of death among adolescents and young adults (AYA). AYA living with perinatally acquired HIV infection (AYALPHIV) are at higher risk of attempted suicide when compared with AYA who were perinatally HIV-exposed but uninfected (AYAPHEU). To inform interventions, we identified risk and protective factors of attempted suicide among AYALPHIV and AYAPHEU. SETTING Data were obtained from a longitudinal New York City-based study of AYALPHIV and AYAPHEU (n = 339; enrollment age 9-16 years) interviewed approximately every 12-18 months. METHOD Our main outcome was suicide attempt at any follow-up. The DISC was used to assess psychiatric disorder diagnoses and attempted suicide and the Child Depression Inventory to assess depressive symptoms. Psychosocial and sociodemographic risk factors were also measured. Analyses used backward stepwise logistic regression modeling. RESULTS At enrollment, 51% was female individuals, 49% Black, 40% Latinx, and 11% both Black and Latinx. Attempted suicide prevalence was significantly higher among AYALPHIV compared with AYAPHEU (27% vs 16%, P = 0.019), with AYALPHIV having 2.21 times the odds of making an attempt [95% confidence interval: (1.18 to 4.12), P = 0.013]. Higher Child Depression Inventory scores were associated with an increased risk of attempted suicide in both groups and the total sample. The presence of DISC-defined behavior disorder increased the risk of attempted suicide in the total sample and the AYALPHIV subgroup. Religiosity was protective of attempted suicide in AYALPHIV. CONCLUSIONS AYALPHIV had increased suicide attempts compared with AYAPHEU. Religiosity was protective in AYALPHIV. Highlighting a need for prevention of early mental health challenges was associated with risk.

Introduction Existing research on postabortion emergency room visits is sparse and limited by methods which underestimate the incidence of adverse events following abortion. Postabortion emergency room (ER) use since Food and Drug Administration approval of chemical abortion in 2000 can identify trends in the relative morbidity burden of chemical versus surgical procedures. Objective To complete the first longitudinal cohort study of postabortion emergency room use following chemical and surgical abortions. Methods A population-based longitudinal cohort study of 423 000 confirmed induced abortions and 121,283 subsequent ER visits occurring within 30 days of the procedure, in the years 1999-2015, to Medicaid-eligible women over 13 years of age with at least one pregnancy outcome, in the 17 states which provided public funding for abortion. Results ER visits are at greater risk to occur following a chemical rather than a surgical abortion: all ER visits (OR 1.22, CL 1.19-1.24); miscoded spontaneous (OR 1.88, CL 1.81-1.96); and abortion-related (OR 1.53, CL 1.49-1.58). ER visit rates per 1000 abortions grew faster for chemical abortions, and by 2015, chemical versus surgical rates were 354.8 versus 357.9 for all ER visits; 31.5 versus 8.6 for miscoded spontaneous abortion visits; and 51.7 versus 22.0 for abortion-related visits. Abortion-related visits as a percent of total visits are twice as high for chemical abortions, reaching 14.6% by 2015. Miscoded spontaneous abortion visits as a percent of total visits are nearly 4 times as high for chemical abortions, reaching 8.9% of total visits and 60.9% of abortion-related visits by 2015. Conclusion The incidence and per-abortion rate of ER visits following any induced abortion are growing, but chemical abortion is consistently and progressively associated with more postabortion ER visit morbidity than surgical abortion. There is also a distinct trend of a growing number of women miscoded as receiving treatment for spontaneous abortion in the ER following a chemical abortion.

Osteomyelitis is a common occurrence in children and typically has a prolonged treatment course involving multiple specialties. Historically, the long bones are most commonly affected and Staphylococcus aureus is the primary causative organism.This case shows the value of using the Kocher criteria and acute phase reactant C-reactive protein as diagnostic tools that can be used to advocate MRI to rule out this potentially devastating process.

Objective: As veterans have high rates of posttraumatic stress disorder (PTSD) and historically poor treatment outcomes and high attrition, alternative treatments have gained much popularity despite lack of rigorous research. In this study, a recently developed and manualized 8-session group Equine-Assisted Therapy for PTSD (EAT-PTSD) was tested in an open trial to assess its preliminary feasibility, acceptability, and outcomes for military veterans. Methods: The study was conducted from July 2016 to July 2019. Sixty-three treatment-seeking veterans with PTSD enrolled. PTSD diagnosis was ascertained using the Structured Clinical Interview for DSM-5, Research Version (SCID-5-RV) and confirmed using the Clinician-Administered PTSD Scale (CAPS-5). Mean age was 50 years, and 23 patients (37%) were women. Clinician and self-report measures of PTSD and depression were assessed at pretreatment, midtreatment, and posttreatment and at a 3-month follow-up. An intent-to-treat analysis and a secondary analysis of those who completed all 4 clinical assessments were utilized. Results: Only 5 patients (8%) withdrew from treatment, 4 before midtreatment and 1 afterward. Posttreatment assessment revealed marked reductions in both clinician-rated and self-reported PTSD and depression symptoms, which persisted at 3-month follow-up. Specifically, mean (SD) CAPS-5 scores fell from 38.6 (8.1) to 26.9 (12.4) at termination. Thirty-two patients (50.8%) showed clinically significant change (≥ 30% decrease in CAPS-5 score) at posttreatment and 34 (54.0%) at follow-up. Conclusions: Manualized EAT-PTSD shows promise as a potential new intervention for veterans with PTSD. It appears safe, feasible, and clinically viable. These preliminary results encourage examination of EAT-PTSD in larger, randomized controlled trials. Trial Registration: ClinicalTrials.gov identifier: NCT03068325.

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Introduction: The prevalence of induced abortion among women with children has been estimated indirectly by projections derived from survey research. However, an empirically derived, population-based conclusion on this question is absent from the published literature. Objective: The objective of this study was to describe the period prevalence of abortion among all other possible pregnancy outcomes within the reproductive histories of Medicaid-eligible women in the U.S. Methods: A retrospective, cross-sectional, longitudinal analysis of the pregnancy outcome sequences of eligible women over age 13 from the 17 states where Medicaid included coverage of most abortions, with at least one identifiable pregnancy between 1999 and 2014. A total of 1360 pregnancy outcome sequences were grouped into 8 categories which characterize various combinations of the 4 possible pregnancy outcomes: birth, abortion, natural loss, and undetermined loss. The reproductive histories of 4,884,101 women representing 7,799,784 pregnancy outcomes were distributed into these categories. Results: Women who had live births but no abortions or undetermined pregnancy losses represented 74.2% of the study population and accounted for 87.6% of total births. Women who have only abortions but no births constitute 6.6% of the study population, but they are 53.5% of women with abortions and have 51.5% of all abortions. Women with both births and abortions represent 5.7% of the study population and have 7.2% of total births. Conclusion: Abortion among low-income women with children is exceedingly uncommon, if not rare. The period prevalence of mothers without abortion is 13 times that of mothers with abortion.

Shortened versions of self-reported questionnaires may be used to reduce respondent burden. When shortened screening tools are used, it is desirable to maintain equivalent diagnostic accuracy to full-length forms. This manuscript presents a case study that illustrates how external data and individual participant data meta-analysis can be used to assess the equivalence in diagnostic accuracy between a shortened and full-length form. This case study compares the Patient Health Questionnaire-9 (PHQ-9) and a 4-item shortened version (PHQ-Dep-4) that was previously developed using optimal test assembly methods. Using a large database of 75 primary studies (34,698 participants, 3,392 major depression cases), we evaluated whether the PHQ-Dep-4 cutoff of ≥ 4 maintained equivalent diagnostic accuracy to a PHQ-9 cutoff of ≥ 10. Using this external validation dataset, a PHQ-Dep-4 cutoff of ≥ 4 maximized the sum of sensitivity and specificity, with a sensitivity of 0.88 (95% CI 0.81, 0.93), 0.68 (95% CI 0.56, 0.78), and 0.80 (95% CI 0.73, 0.85) for the semi-structured, fully structured, and MINI reference standard categories, respectively, and a specificity of 0.79 (95% CI 0.74, 0.83), 0.85 (95% CI 0.78, 0.90), and 0.83 (95% CI 0.80, 0.86) for the semi-structured, fully structured, and MINI reference standard categories, respectively. While equivalence with a PHQ-9 cutoff of ≥ 10 was not established, we found the sensitivity of the PHQ-Dep-4 to be non-inferior to that of the PHQ-9, and the specificity of the PHQ-Dep-4 to be marginally smaller than the PHQ-9.

The recent Translations article by Bishop et al.1 draws much-needed attention to social communication (SC) in autism spectrum disorder (ASD) and to the need in autism research for treatment-sensitive measures of this key domain. In this context, the authors define SC ability as "the appropriate use and modulation of verbal and nonverbal behaviors during interactions with others"1(p. 555). "Appropriate" is defined relative to normative behaviors for developmental age and language level based on parent report. This stirred us to share our concern that clinicians, too, need ways to assess SC. Historically, observation of a patient's SC has not been part of the routine psychiatric mental status examination (MSE); clinicians lack even a common basic vocabulary for describing this vital domain. The DSM-52 does not explicitly define SC or distinguish it from social interaction (SI) or language, important terms also used in the criteria for ASD. All three terms are used interchangeably and inconsistently across the literature. Here we offer a definition of SC, distinguish it from SI and language, and propose a schema, or conceptual model, for observing and documenting an impression of a patient's SC.

Treatment of differentiated thyroid cancer often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. However, there is morbidity associated with I-131 therapy, which can result in both acute and chronic complications. Currently, there are no approved radioprotectors that can be used in conjunction with I-131 to reduce complications in thyroid cancer therapy. It is well known that the damaging effects of ionizing radiation are mediated, in part, by the formation of reactive oxygen species (ROS). A potent scavenger of ROS, Mn(III)meso-tetrakis(N–n-butoxyethylpyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP), has radioprotective and anti-tumor effects in various cancer models including head and neck, prostate, and brain tumors exposed to external beam radiation therapy. Female C57BL/6 mice were administered I-131 orally at doses of 0.0085–0.01 mCi/g (3.145 × 105 to 3.7 × 105 Bq) of body weight with or without MnTnBuOE-2-PyP. We measured acute external inflammation, blood cell counts, and collected thyroid tissue and salivary glands for histological examination. We found oral administration of I-131 caused an acute decrease in platelets and white blood cells, caused facial swelling, and loss of thyroid and salivary tissues. However, when MnTnBuOE-2-PyP was given during and after I-131 administration, blood cell counts remained in the normal range, less facial inflammation was observed, and the salivary glands were protected from radiation-induced killing. These data indicate that MnTnBuOE-2-PyP may be a potent radioprotector of salivary glands in thyroid cancer patients receiving I-131 therapy.

Clinicians regularly use both indirect and direct assessments to identify preferred stimuli to include in control conditions and positive reinforcement test conditions in a functional analysis (FA). However, clinicians often rely on indirect assessment alone (e.g., caregiver report) to identify aversive stimuli to include in negative reinforcement test conditions. In this study, we evaluate a paired-stimulus demand analysis and validate assessment results via FA. Results indicate that, for all 4 participants, the demands selected least often evoked higher rates of destructive behavior than more frequently selected demands. We identified an escape function for all 4 participants in the escape-least selected (LS) condition (true positive finding) and for only 1 participant in the escape-most selected (MS) condition (false negative finding for 3 of 4 participants). These results support the utility of empirically deriving stimuli for inclusion in the negative reinforcement test condition of an FA to decrease the likelihood of false negative findings.

Ciliated hepatic foregut cyst (CHFC) is a rare benign cyst of the liver derived from an embryonic remnant of foregut epithelium. CHFC is typically asymptomatic and is found incidentally. Recent reports of malignant transformation may warrant surgical removal of CHFC. We present the case of a 54-year-old male who was discovered to have a CHFC while undergoing kidney transplant evaluation.

Functional communication training is a commonly used and effective treatment for socially reinforced destructive behavior. However, when a functional analysis suggests that destructive behavior is multiply controlled (e.g., by attention, tangibles, and escape), teaching and evaluating separate functional communication responses (FCRs) can be time-consuming or only partially effective when failing to address multiple establishing operations that may occur simultaneously. We evaluated the use of an omnibus FCR or mand that produced access to attention, tangibles, and escape within each functional-analysis test condition for two boys with autism spectrum disorder who displayed multiply controlled destructive behavior. The omnibus-FCR treatment produced low rates of destructive behavior and high percentages of independent FCRs within each condition for both children, suggesting that such a treatment option may reduce destructive behavior and teach communication skills quickly prior to introducing other treatment components, such as teaching individual FCRs to address each unique function of destructive behavior.

Prior research has shown that bringing functional communication responses under the discriminative control of schedule-correlated stimuli facilitates rapid reinforcement schedule thinning and the transfer of functional communication training (FCT) treatment effects to other therapists and settings. In Experiment 1, we extended this body of research by rapidly transferring FCT treatment effects to a caregiver, despite the caregiver's unique and lengthy history of reinforcement of the child's destructive behavior. In Experiment 2, we evaluated the degree to which FCT treatment effects transferred to another participant's caregivers when the caregivers implemented FCT with and without schedule-correlated stimuli. Rapid transfer of FCT treatment effects occurred only when caregivers used the schedule-correlated stimuli. We discuss the use of schedule-correlated stimuli within FCT procedures as a method of programming for generalization when extending treatment to caregivers.

Food selectivity is a common problem for children with autism spectrum disorder (ASD; Schreck, Williams, & Smith, 2004). Behavior-analytic interventions have the most empirical support for feeding disorders (Sharp, Jaquess, Morton, & Miles, 2011). However, there are no randomized controlled trials that have evaluated its effects with a well-defined cohort of children with ASD. In the current investigation, we randomly assigned 6 young children with ASD and food selectivity to either an applied behavior analytic intervention or a wait-list control. We used a crossover randomized controlled trial to evaluate the effects of a multicomponent applied behavior analytic intervention on independent acceptance and mouth clean of 16 novel foods. We subsequently exposed the wait-list control group to the intervention. We also evaluated the effects of the intervention on individual participants with single-case designs. The percentage of independent acceptance and mouth clean increased for the applied behavior analytic intervention group, but not for the wait-list control group until we implemented the intervention.

Fitted algebraic equations with probability distributions are presented to predict the maturation of selected physiological parameters that occur postnatally in preterm and term neonates through early infancy. The neonatal population, in particular preterm neonates, remains a challenge for the development of physiologically based pharmacokinetic (PBPK) models. The need to make available these building blocks for PBPK models for this age group is important for this field to advance. While the equations do not represent an exhaustive evaluation of anatomy, equations with 90% prediction intervals, where data permits, are presented for body weight, organ and tissue growth, blood flows, cardiac output, plasma albumin concentration, and glomerular filtration rate. Ontogeny measurements for blood flows to organs and tissues are limited. Longitudinal anthropomorphic measurements versus intrauterine or newborn measurements in preterm neonates would help reduce the uncertainty in the growth trajectories of neonates.

Children with autism spectrum disorder (ASD) often display impaired listener skills, and few studies have evaluated procedures for establishing initial auditory-visual conditional discrimination skills. We developed and evaluated a treatment package for training initial auditory-visual conditional discriminations based on the extant research on training such discriminations in children with ASD with at least some preexisting skills in this area. The treatment package included (a) conditional-only training, (b) prompting the participant to echo the sample stimulus as a differential observing response, (c) prompting correct selection responses using an identity-match prompt, (d) using progressively delayed prompts, and (e) repeating trials until the participant emitted an independent correct response. Results indicated all participants mastered all listener targets, and the two participants for whom we tested the emergence of corresponding tacts showed mastery of most tacts without direct training. We discuss these results relative to prior research on listener skills and tacts.

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring. Genotyping of somatic cells as well as brain biopsies confirmed mutations in the SHANK3 gene and reduced levels of SHANK3 protein in these macaques. Analysis of data from functional magnetic resonance imaging revealed altered local and global connectivity patterns that were indicative of circuit abnormalities. The founder mutants exhibited sleep disturbances, motor deficits and increased repetitive behaviours, as well as social and learning impairments. Together, these results parallel some aspects of the dysfunctions in the SHANK3 gene and circuits, as well as the behavioural phenotypes, that characterize autism spectrum disorder and Phelan-McDermid syndrome.

Behavioral and Psychological Symptoms of Dementia (BPSD), present in almost 90% of patients with Alzheimer’s Disease (AD), cause extensive impairment leading to reduced independence and inability to complete activities of daily living. Though BPSD includes a wide range of symptoms, such as agitation, aggression, disinhibition, anxiety, depression, apathy, delusions, and hallucinations. Certain BPSD in AD co-present and can be clustered into distinct domains based on their frequency of co-occurrence. As these BPSD are so pervasive in any stages of AD, the disease may be better characterized as a disorder of heterogeneous degenerative symptoms across a number of symptom domains, with the most prominent domain comprising memory and cognitive deficits. Importantly, there are no FDA-approved drugs to treat these BPSD, and new approaches must be considered to develop effective treatments for AD patients. The biogenic monoamine 5-hydroxytryptamine (5-HT), or serotonin, works as both a neurotransmitter and neuromodulator, which has been tied to cognitive decline and multiple BPSD domains. This review summarizes the evidence for specific serotonergic system alterations across some of the well-studied cognitive, behavioral, and psychiatric domains. Though differences in overall serotonergic transmission occur in AD, circuit-specific alterations in individual 5-HT receptors (5-HTRs) are likely linked to the heterogeneous presentation of BPSD in AD.

Under naturally occurring conditions, the individual who is the target of aggression is likely to physically react to evade the aggressor and avoid physical harm. Like other forms of attention that occur following problem behavior, physical reactions may maintain problem behavior. However, evaluating the effects of physical reactions is complicated by issues related to therapists' ability to consistently and safely control their reactions, which may prove difficult to achieve in functional analyses. We evaluated the utility of a concurrent-operant analysis to test behavioral sensitivity to physical reactions. The results suggest that the concurrent-operant analysis may be useful when therapists cannot consistently refrain from responding contingent on problem behavior in the control condition of a more typical functional analysis.

The Military Family Wellness Center at Columbia University Irving Medical Center provides cost-free, confidential mental health services to military service members, veterans, and their families in a nongovernmental setting, with an emphasis on addressing gaps in available care. Partnerships with academic institutions and collaboration with veteran organizations, regional stakeholders, and local Veterans Administration centers facilitate cross-site referrals, enhance knowledge and expertise, and advance shared goals. This article describes the development of these relationships, focusing on key priorities, barriers overcome, and lessons learned. Future directions are discussed.

This study examined clinician experiences and attitudes toward safety planning in a large urban pediatric psychiatry department serving primarily Latino youth. A total of 46 clinicians completed a survey assessing their experience with and attitudes toward safety planning with adolescents at-risk for suicide. The majority of clinicians were female (78%), non-Latino White (54%), and aged 30-39 (52%). Clinicians' attitudes were largely positive (M = 3.69 SD = 0.47, Range = 2.42-4.42). However, many clinicians (n = 24) were not convinced that safety planning reduces the imminent risk of suicidal behavior in patients. This study provides more depth to our understanding of the way in which safety planning is perceived by clinicians.

Arsenic is a ubiquitous contaminant, with typical human dietary intake below 1 μg/kg bw/d and extreme drinking water exposures up to ∼50 μg/kg bw/d. The formation and binding of trivalent metabolites are central to arsenic toxicity and strong human evidence suggests special concern for early life exposures in the etiology of adult diseases, especially cancer. This study measured the metabolism and disposition of arsenite in neonatal mice to understand the role of maturation in metabolic activation and detoxification of arsenic. Many age-related differences were observed after gavage administration of arsenite, with consistent evidence in blood and tissues for higher exposures to trivalent arsenic species in neonatal mice related to the immaturity of metabolic and/or excretory functions. The evidence for greater tissue binding of arsenic species in young mice is consistent with enhanced susceptibility to toxicity based on metabolic and toxicokinetic differences alone. Lactational transfer from arsenite-dosed dams to suckling mice was minimal, based on no dosing-related changes in the levels of arsenic species in pup blood or milk collected from the dams. Animal models evaluating whole-life exposure to inorganic arsenic must use direct dosing in early neonatal life to predict accurately potential toxicity from early life exposures in children.

The objective of this study was to develop pediatric physiologically based pharmacokinetic (PBPK) models for pantoprazole and esomeprazole. Pediatric PBPK models were developed by Simcyp version 15 by incorporating cytochrome P450 (CYP)2C19 maturation and auto‐inhibition. The predicted‐to‐observed pantoprazole clearance (CL) ratio ranged from 0.96–1.35 in children 1–17 years of age and 0.43–0.70 in term infants. The predicted‐to‐observed esomeprazole CL ratio ranged from 1.08–1.50 for children 6–17 years of age, and 0.15–0.33 for infants. The prediction was markedly improved by assuming no auto‐inhibition of esomeprazole in infants in the PBPK model. Our results suggested that the CYP2C19 auto‐inhibition model was appropriate for esomeprazole in adults and older children but could not be directly extended to infants. A better understanding of the complex interplay of enzyme maturation, inhibition, and compensatory mechanisms for CYP2C19 is necessary for PBPK modeling in infants.

Children with autism spectrum disorder (ASD) have difficulty generalizing from directly trained responses to untrained responses (i.e., emergent responding). In this study, we used a chain prompt combined with matrix training to teach 2 participants with ASD to tact 192 three-digit numerals. We used a multiple-baseline design across matrices to evaluate the treatment effects on trained and untrained tacts of numerals. Both participants mastered all numerals exposed to training and all numerals not exposed to training after 3 to 5 sixteen-trial sessions per matrix. One participant learned to tact 8 numerals for each 1 numeral exposed to direct training, and the other participant learned to tact 12 numerals for each 1 numeral exposed to direct training. We discuss these results relative to the effectiveness and efficiency of our chain prompt combined with matrix training for teaching tacting skills for targets with shared stimulus properties that facilitate generalization to untrained targets.