Inpatient Care Utilization Following Mobile Crisis Response Encounters Among Racial/Ethnic Minoritized Youth.

OBJECTIVE: There has been an increase in youth psychiatric emergencies and psychiatric inpatient hospitalizations in recent years. Mobile crisis response (MCR) services offer an opportunity to meet acute youth mental health needs in the community and to provide linkage to care. However, an understanding of MCR encounters as a care pathway is needed, including how patterns of subsequent care may vary by youth race/ethnicity. The current study examines racial/ethnic differences in the rates of inpatient care use following MCR among youth. METHOD: Data included Los Angeles County Department of Mental Health (LACDMH) administrative claims for MCR in 2017 and psychiatric inpatient hospitalizations and outpatient services from 2017-2020 for youth aged 0 to 18 years. RESULTS: In this sample of 6,908 youth (70.4% racial/ethnic minoritized youth) who received an MCR, 3.2% received inpatient care within 30 days of their MCR, 18.6% received inpatient care beyond 30 days of their MCR, and 14.7% received repeated inpatient care episodes during the study period. Multivariate models revealed that Asian American/Pacific Islander (AAPI) youth were less likely to receive inpatient care, whereas American Indian/Alaska Native (AI/AN) youth were more likely to receive inpatient care following MCR. Youth age, primary language, primary diagnosis, and insurance status also predicted future inpatient episodes. CONCLUSION: Findings highlight differential rates of inpatient use following MCR among AAPI and AI/AN youth relative to youth from other groups. Alternative interpretations for the findings are offered related to differential levels of need and disparate penetration of community-based outpatient and prevention-focused services.

After the Crisis: Racial/Ethnic Disparities and Predictors of Care Use Following Youth Psychiatric Emergencies.

OBJECTIVE: Youth psychiatric emergencies have increased at alarming rates, and disproportionately so for youth of color. Outpatient follow-up care is critical for positive youth outcomes, but rates of follow-up remain low, especially for racial/ethnic minoritized youth. Mobile crisis response can initiate care connection. The current study (1) describes the population who received mobile crisis response (MCR) within the nation's largest county public mental health system, (2) assesses rates of follow-up outpatient services after MCR, and (3) examines racial/ethnic disparities in outpatient services and correlates of receipt of therapy dose (≥8 sessions). METHOD: Administrative claims for MCR and outpatient services for youth ages 0 to 18 were abstracted from the Los Angeles County Department of Mental Health. RESULTS: From October 2016-2019, 20,782 youth received a MCR, 52.5% of youth were female, and youth mean age was 13.41 years. The majority of youth (91.8%) received some outpatient services after their first MCR. However, only 56.7% of youth received ≥1 therapy session. In a logistic regression, youth age, gender, race/ethnicity, primary language, primary diagnosis, insurance status, MCR call location, and MCR disposition significantly predicted receipt of ≥8 therapy sessions. CONCLUSIONS: Findings highlight disparities in therapy receipt for Asian American Pacific Islander, Black, and White youth (relative to Latinx youth), older youth, youth whose MCR was initiated from a police station call, and youth whose MCR did not result in hospitalization. We discuss priorities for quality improvement for MCR processes and strategies to promote linkage to care to achieve mental health equity.

Integrating blue: How do we make nationally determined contributions work for both blue carbon and local coastal communities?

Blue Carbon Ecosystems (BCEs) help mitigate and adapt to climate change but their integration into policy, such as Nationally Determined Contributions (NDCs), remains underdeveloped. Most BCE conservation requires community engagement, hence community-scale projects must be nested within the implementation of NDCs without compromising livelihoods or social justice. Thirty-three experts, drawn from academia, project development and policy, each developed ten key questions for consideration on how to achieve this. These questions were distilled into ten themes, ranked in order of importance, giving three broad categories of people, policy & finance, and science & technology. Critical considerations for success include the need for genuine participation by communities, inclusive project governance, integration of local work into national policies and practices, sustaining livelihoods and income (for example through the voluntary carbon market and/or national Payment for Ecosystem Services and other types of financial compensation schemes) and simplification of carbon accounting and verification methodologies to lower barriers to entry.

Assessing intertidal seagrass beds relative to water quality in Vanuatu, South Pacific.

Seagrasses are globally important, but their extent is decreasing due to the impact of human activities and changing climatic conditions. Seagrass meadows provide vital services, but their condition and distribution are not yet well known, particularly in many small tropical Pacific islands. In 2018, observations and samples were collected from intertidal seagrasses of Efate Island, Vanuatu (South Pacific). Observations included canopy height, percentage cover, growth rate and species variety. Water quality samples were also collected in some locations. Our seagrass metrics suggested more challenging conditions for the seagrasses near Port Vila, the main urban area in the island, where water quality analyses indicated higher levels of dissolved inorganic nitrogen and suspended solids.

Computational Thinking Is More about Thinking than Computing.

Computational thinking is widely recognized as important, not only to those interested in computer science and mathematics but also to every student in the twenty-first century. However, the concept of computational thinking is arguably complex; the term itself can easily lead to direct connection with "computing" or "computer" in a restricted sense. In this editorial, we build on existing research about computational thinking to discuss it as a multi-faceted theoretical nature. We further present computational thinking, as a model of thinking, that is important not only in computer science and mathematics, but also in other disciplines of STEM and integrated STEM education broadly.

Development of a multisystem surveillance database for transfusion-transmitted infections among blood donors in the United States.

BACKGROUND: The frequency of positive test results for transfusion-transmitted infections (TTIs) among blood donors is an important index of safety; thus, appropriate monitoring is critical, particularly when there are changes in policies affecting donor suitability. STUDY DESIGN AND METHODS: Testing algorithms from three large blood systems were reviewed and consensus definitions for a surveillance-positive result for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) established. In addition, information on each donation, including donor demographics and location, was collected. Combined data were analyzed to characterize the epidemiology of TTIs by person, place, and time. RESULTS: Data from 14.8 million donations were collected for 2011 to 2012, representing more than 50% of the US blood supply. Surveillance-positive rates per 10,000 donations were as follows: HBV, 0.76; HCV, 2.0; HIV, 0.28; and HTLV 0.34. Rates did not vary between the 2 years, although there was variation within a year. With the exception of HTLV, rates were higher among males, and all rates were higher among first-time donations. Window-period donations (those positive only in nucleic acid tests) were infrequent (HBV, 13; HCV, 60; HIV, 14) during the 2-year period. Frequencies of surveillance-positive results varied by donor age and residence location. CONCLUSIONS: We demonstrated that standardized data from multiple major US blood systems can be combined and analyzed for change. However, TTI frequencies are low, impacting their sensitivity to change. Furthermore, observed fluctuations in TTI frequencies may be secondary to changes in blood donor demographics rather than necessarily reflecting the immediate impact of policy modification.

A randomized controlled trial of the web-based OurRelationship program: Effects on relationship and individual functioning.

OBJECTIVE: Within the United States, one third of married couples are distressed and almost half of first marriages (and more than half of unmarried cohabiting relationships) end in divorce/separation. Additionally, relationship distress has been linked to mental and physical health problems in partners and their children. Although couple therapy is effective in reducing relationship distress, it is utilized by less than one third of divorcing couples. Therefore, more accessible interventions for relationship distress are needed. METHOD: This study tests the efficacy of the OurRelationship program, an 8-hr online program adapted from an empirically based, in-person couple therapy. In the program, couples complete online activities and have 4 15-min calls with project staff. Nationwide, 300 heterosexual couples (N = 600 participants) participated; couples were generally representative of the US in terms of race, ethnicity, and education. Couples were randomly assigned to begin the program immediately or to a 2-month waitlist control group. RESULTS: Compared to the waitlist group, intervention couples reported significant improvements in relationship satisfaction (Cohen's d = 0.69), relationship confidence (d = 0.47), and negative relationship quality (d = 0.57). Additionally, couples reported significant improvements in multiple domains of individual functioning, especially when individuals began the program with difficulties in that domain: depressive (d = 0.71) and anxious symptoms (d = 0.94), perceived health (d = 0.51), work functioning (d = 0.57), and quality of life (d = 0.44). CONCLUSIONS: In a nationally representative sample of couples, the OurRelationship program was effective in significantly improving both relationship and individual functioning, suggesting it can substantially increase the reach of current interventions through its low-cost, Web-based format.

Reply to the commentaries: Of course, we do not yet know what it is all about, but functional contextualism is a good place to start.

In this reply to the commentaries, we note several points of disagreement with Johnson and Greenman on theoretical and empirical grounds. We are particularly surprised by their assumption that attachment has already been established as the key mechanism of change in couple therapy, as our present findings do not support this idea. We also elaborate on Gurman's functional contextualist views and describe why IBCT may be a particularly helpful model for training new couple therapists in a contextualist way.

Pharmacokinetics, bioavailability, and hemodynamic effects of trazodone after intravenous and oral administration of a single dose to dogs.

OBJECTIVE: To determine the pharmacokinetics and hemodynamic effects of trazodone after IV and oral administration in dogs and bioavailability after oral administration. ANIMALS: 6 adult Beagles. PROCEDURES: Dogs received trazodone HCl (8 mg/kg) orally and IV in a randomized controlled crossover design. Blood samples were collected at various times after administration. Heart rates and indirectly measured blood pressures of dogs and plasma concentrations and pharmacokinetics of trazodone were determined. RESULTS: Following IV administration, the mean ± SD elimination half-life, apparent volume of distribution, and plasma total body clearance were 169 ± 53 minutes, 2.53 ± 0.47 L/kg, and 11.15 ± 3.56 mL/min/kg, respectively. Following oral administration, the mean ± SD elimination half-life and absolute bioavailability were 166 ± 47 minutes and 84.6 ± 13.2%, respectively. Maximum plasma concentration following oral administration was 1.3 ± 0.5 µ/mL, and time to maximum plasma concentration was 445 ± 271 minutes. After IV administration, all dogs immediately developed transient tachycardia (184.3 ± 8.0 beats/min), and 3 of 6 dogs developed aggression. Increase in heart rate was significantly associated with increase in plasma drug concentration following IV administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicated oral administration of trazodone resulted in acceptable absolute bioavailability, with substantial variability in time to maximum plasma concentration. Individualized approaches in dosing intervals may be necessary for dogs receiving oral trazodone. An orally administered dose of 8 mg/kg was well tolerated in dogs; IV administration of a dose of 8 mg/kg caused substantial adverse effects, including tachycardia and behavior disinhibition.

Translation of Integrative Behavioral Couple Therapy to a web-based intervention.

Couple therapy-across a number of different theoretical approaches-has been shown to be an effective treatment for a variety of individual and relationship difficulties. Moreover, recent studies have demonstrated that the effects of several approaches last at least 2-5 years after the end of treatment. However, couple therapy has a critical limitation: most distressed couples--including those who eventually divorce--do not seek couple therapy. Thus, although we recognize there are notable advances in the treatment approaches described in this special section, we argue that traditional approaches to couple therapy need to be supplemented by alternative interventions before we can make a profound, population-level impact on relationship distress and divorce. To this end, we translated Integrative Behavioral Couple Therapy into a self-help, web-based program-www.OurRelationship.com. Through a combination of tailored feedback, filmed examples, and interactive education, the online program first helps couples identify a core problem in their relationship. The program then assists partners in coming to a new and more accurate understanding of the problem they jointly identified and subsequently brings them together in a structured conversation to share their new understandings with each other. Finally, based on this shared conceptualization, the program supports couples in making concrete changes in their relationship. In this article, we discuss the rationale for the program, describe the core components of the website, and illustrate these components with a case example. Relative advantages and disadvantages compared with traditional couple therapy are presented.

The impact of behavioral couple therapy on attachment in distressed couples.

Emotion-focused therapy (EFT; Greenberg & Johnson, Emotionally focused therapy for couples. New York: Guilford Press) is anchored in attachment theory (Johnson, 2003 Attachment processes in couples and families. New York: Guilford) and considers change in attachment schemas essential in the process of improving satisfaction in relationships (Johnson, 1999, Research and couples therapy: Where do we go from here? American Family Therapy Academy Newsletter). However, there are little data on how measures of attachment change over the course of EFT or any other couple therapy. The current study examines whether increases in attachment security predict improvements in marital satisfaction during behavioral couple therapy, which would suggest that change in attachment style is a key process variable even for a non-attachment-focused treatment. Multilevel models of data from 134 couples participating in a randomized clinical trial of integrative behavioral couple therapy and traditional behavioral couple therapy (Christensen et al. Journal of Consulting and Clinical Psychology, 72, 2004, 176) indicate that although there is a trend for early change in attachment-related anxiety and avoidance to predict later change in marital satisfaction, early change in marital satisfaction strongly predicts change in attachment-related anxiety through the end of treatment and 2-year follow-up. These findings suggest that changes in satisfaction may lead to changes in attachment rather than the reverse and that change in attachment may not be the mechanism of change in all efficacious couple therapy.

Validation of a high-throughput, automated electrophysiology platform for the screening of nicotinic agonists and antagonists.

High-throughput compound screening using electrophysiology-based assays represents an important tool for biomedical research and drug discovery programs. The recent development and availability of devices capable of performing high-throughput electrophysiology-based screening have brought the need to validate these tools by producing data that are consistent with results obtained with conventional electrophysiological methods. In this study, we compared the response properties of hα3ß4 and hα4ß2 nicotinic receptors to their endogenous ligand acetylcholine (ACh) using three separate electrophysiology platforms: Dynaflow (low-throughput, manual system), PatchXpress 7000A (medium-throughput automated platform), and IonWorks Barracuda (high-throughput automated platform). We found that despite the differences in methodological approaches between these technologies, the EC(50) values from the ACh dose-response curves were consistent between all three platforms. In addition, we have validated the IonWorks Barracuda for both competitive and uncompetitive inhibition assays by using the competitive nicotinic antagonist dihydro-beta-erythroidin (DHßE) and uncompetitive nicotinic antagonist mecamylamine. Furthermore, we have demonstrated the utility of a custom-written algorithm for generating dose-response curves from multiple extrapolated current metrics that allows for discriminating between competitive and uncompetitive inhibition while maintaining high-throughput capacity. This study provides validation of the consistency of results using low-, medium-, and high-throughput electrophysiology platforms and supports their use for screening nicotinic compounds.

Functional and structural interaction of (-)-reboxetine with the human α4ß2 nicotinic acetylcholine receptor.

The interaction of the selective norepinephrine reuptake inhibitor (-)-reboxetine with the human α4ß2 nicotinic acetylcholine receptor (nAChR) in different conformational states was studied by several functional and structural approaches. Patch-clamp and Ca(2+)-influx results indicate that (-)-reboxetine does not activate hα4ß2 nAChRs via interaction with the orthosteric sites, but inhibits agonist-induced hα4ß2 activation by a noncompetitive mechanism. Consistently, the results from the electrophysiology-based functional approach suggest that (-)-reboxetine may act via open channel block; therefore, it is capable of producing a use-dependent type of inhibition of the hα4ß2 nAChR function. We tested whether (-)-reboxetine binds to the luminal [(3)H]imipramine site. The results indicate that, although (-)-reboxetine binds with low affinity to this site, it discriminates between the resting and desensitized hα4ß2 nAChR ion channels. Patch-clamp results also indicate that (-)-reboxetine progressively inhibits the hα4ß2 nAChR with two-fold higher potency at the end of one-second application of agonist, compared with the peak current. The molecular docking studies show that (-)-reboxetine blocks the ion channel at the level of the imipramine locus, between M2 rings 6' and 14'. In addition, we found a (-)-reboxetine conformer that docks in the helix bundle of the α4 subunit, near the middle region. According to molecular dynamics simulations, (-)-reboxetine binding is stable for both sites, albeit less stable than imipramine. The interaction of these drugs with the helix bundle might alter allostericaly the functionality of the channel. In conclusion, the clinical action of (-)-reboxetine may be produced (at least partially) by its inhibitory action on hα4ß2 nAChRs.

Discovery of (2S,3R)-N-[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]furan-2-carboxamide (TC-5619), a selective α7 nicotinic acetylcholine receptor agonist, for the treatment of cognitive disorders.

(2S,3R)-N-[2-(Pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]furan-2-carboxamide (7a, TC-5619), a novel selective agonist of the α7 neuronal nicotinic acetylcholine receptor, has been identified as a promising drug candidate for the treatment of cognitive impairment associated with neurological disorders. 7a demonstrated more than a thousand-fold separation between the affinities for the α7 and α4ß2 receptor subtypes and had no detectable effects on muscle or ganglionic nicotinic receptor subtypes, indicating a marked selectivity for the central nervous system over the peripheral nervous system. Results obtained from homology modeling and docking explain the observed selectivity. 7a had positive effects across cognitive, positive, and negative symptoms of schizophrenia in animal models and was additive or synergistic with the antipsychotic clozapine. Compound 7a, as an augmentation therapy to the standard treatment with antipsychotics, demonstrated encouraging results on measures of negative symptoms and cognitive dysfunction in schizophrenia and was well tolerated in a phase II clinical proof of concept trial in patients with schizophrenia.

Structure-activity studies of 7-heteroaryl-3-azabicyclo[3.3.1]non-6-enes: a novel class of highly potent nicotinic receptor ligands.

The potential for nicotinic ligands with affinity for the α4ß2 or α7 subtypes to treat such diverse diseases as nicotine addiction, neuropathic pain, and neurodegenerative and cognitive disorders has been exhibited clinically for several compounds while preclinical activity in relevant in vivo models has been demonstrated for many more. For several therapeutic programs, we sought nicotinic ligands with various combinations of affinity and function across both subtypes, with an emphasis on dual α4ß2-α7 ligands, to explore the possibility of synergistic effects. We report here the structure-activity relationships (SAR) for a novel series of 7-heteroaryl-3-azabicyclo[3.3.1]non-6-enes and characterize many of the analogues for activity at multiple nicotinic subtypes.

Common principles of couple therapy.

The similarity in efficacy of evidence-based couple therapies suggests that it may be useful to identify those treatment principles they hold in common. Expanding on the previous description of a unified protocol for couple therapy (Christensen, 2010), this article outlines five common principles: (a) altering the couple's view of the presenting problem to be more objective, contextualized, and dyadic; (b) decreasing emotion-driven, dysfunctional behavior; (c) eliciting emotion-based, avoided, private behavior; (d) increasing constructive communication patterns; and (e) emphasizing strengths and reinforcing gains. For each of these five elements of the unified protocol, the paper addresses how and to what extent the most common forms of evidence-based couple therapy carry out this principle. Implications for clinical practice, treatment research, and basic research on intimate relationships are discussed.

A method for bidirectional solution exchange--"liquid bullet" applications of acetylcholine to α7 nicotinic receptors.

Fast solution exchange techniques have revolutionized the study of synaptic transmission and promise to remain an important neuroscience research tool. Here we provide evidence for the hypothesis that using continuous, rapid transitions through an agonist solution can significantly increase the exchange rate around a cell by reducing the diffusion boundary at the membrane. This novel approach of rapid solution exchange during whole-cell recordings--described as a "liquid bullet" (LB) application--takes advantage of a bidirectional solution flow around the cell, allowing for a full solution exchange within a range of several milliseconds. An exchange rate (10-90% rise time) of about 2 ms could be achieved during both agonist application and washout. We recorded whole-cell currents from cells expressing the rapidly desensitizing α7 neuronal nicotinic receptor (NNR) subtype that exhibited very fast rise times of around 4-5 ms. We further demonstrated the advantages of a LB application over conventional methods by the ability of this method to elicit concentration-dependent responses for rapidly desensitizing compounds that were not measurable with conventional agonist applications. In addition, we illustrate the utility of this approach for frequency-based assays through fast, repeated agonist applications at frequencies of 1 Hz and 30 Hz. This approach could therefore be useful for the study of rapid agonist-receptor interactions that closely mimic the physiological conditions in the synaptic cleft during bursts of neuronal activity.

Workplace abuse and economic exploitation of children working in the streets of Latin American cities.

This study presents the prevalence of, and factors associated with workplace abuse and economic exploitation among 584 children ages 5 to 17 working in the streets of the Latin American cities of Bogotá, Lima, Quito, and São Paulo. Each additional 10 hours/week of children's work in the streets increased workplace abuse prevalence by 8% (odds ratio [OR], 1.08; 95% confidence interval [95% CI], 1.01-1.19). Suffering an occupational injury was associated with abuse (OR, 1.70; 95% CI, 1.13-2.57). Participation in begging was associated with an almost five-fold increase in economic exploitation (OR, 4.94; 95% CI, 1.96-12.48). Children residing with their mothers were 2.6 times more likely to experience economic exploitation (OR, 2.61; 95% CI, 1.58-4.33), reflecting our definition of economic exploitation in which a child's income is confiscated by parents, even if used for basic family needs. Increased health care coverage and conditional cash transfer programs are recommended to improve the situation.

Biomechanical testing of unstable humeral shaft fracture plating.

This study compared the biomechanical performance of 4.5-mm limited-contact dynamic compression plates (DCPs) and 3.5-mm locking compression plates (LCPs) for the fixation of unstable humeral shaft fractures. Composite humeri were divided into two groups: 3.5-mm LCPs and 4.5-mm DCPs. Osteotomy gaps of 5 mm, simulating diaphyseal comminution, were created. Stiffness tests were performed in anterior-posterior (AP) bending, medial-lateral (ML) bending, torsion, and axial compression. Results showed that while construct stiffnesses in ML bending and torsional loading are significantly higher for the 4.5 DCP group (p < .05), no statistically significant differences were observed in AP bending or axial compression. Fatigue characteristics under cyclic AP bending conditions were also evaluated, although no failures occurred. Data from the literature suggest that stiffness results for the LCP constructs perhaps afford sufficient fixation strength capable of supporting the physiologic loads most commonly applied during postoperative rehabilitation. However, results indicate that the DCP construct is mechanically advantageous for stabilizing diaphyseal comminuted fractures.

Comparison of polyethylene tibial insert damage from in vivo function and in vitro wear simulation.

Function and wear of total knee arthroplasties were compared by analysis of damage patterns on polyethylene tibial inserts retrieved from patients (Group R) with inserts obtained after in vitro force-controlled knee joint wear simulation. Two simulator input profiles were evaluated, including standard walking (Group W), and combined walking and stair descent (Group W + S), simulating varied activities and a more severe physiological environment. Damage regions on all inserts were quantitatively assessed. On average, inserts in all groups had internally rotated damage patterns and the greatest articular deformation in the lateral compartment. These patterns were more pronounced in Group W + S compared to Group W. Deformation rates of simulated inserts were analogous to about six years of physiologic function. However, both groups of simulated inserts generally underestimated the magnitude of damage area and extent observed on retrieved inserts, consistent with differences in the simulator's tibiofemoral contact mechanics and those known to occur in patients during functional activities. Modification of simulator inputs, such as the increased anteroposterior excursion and more severe loading conditions in Group W + S, can generate greater wear volume, larger damage areas, and increased surface deformation rates compared to standard inputs.