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Schools offer an advantageous setting for the prevention, early identification, and treatment of mental health problems for youth. However, school mental health (SMH) services are typically not based on evidence for effectiveness, nor are they efficiently delivered, with SMH practitioners (SMHPs) able to only treat a small number of students in need. The current study evaluated the feasibility, acceptability, efficiency, and outcomes of a four-session assessment, engagement, problem-solving, and triage strategy for SMHPs that aimed to improve efficiency while being based on elements of evidence-based care. The study, conducted in 15 US school districts in three states, used stratified random assignment to assign 49 high schools and their participating SMHP(s) to either the Brief Intervention for School Clinicians (BRISC; N = 259 students) or services as usual (SAU; N = 198 students). SMHPs implemented BRISC elements with adequate to excellent fidelity and reported the strategy was feasible and well-aligned with presenting problems. Students assigned to BRISC reported significantly greater engagement in SMH at 2 months and completion of SMH treatment by 6 months. BRISC-assigned SMHPs reported significantly greater treatment completion after four sessions (53.4%) compared to SAU (15.4%). Students in the BRISC condition also reported significantly greater reduction in problem severity as evaluated by the Youth Top Problems Assessment. No differences were found for anxiety or depression symptoms or overall functioning. Results indicate that BRISC is a feasible early intervention and triage strategy that may aid in more efficient provision of SMH services with no compromise to SMH effectiveness.

Antitumor immunity can be hampered by immunosuppressive mechanisms in the tumor microenvironment, including recruitment of arginase (ARG) expressing myeloid cells that deplete l-arginine essential for optimal T-cell and natural killer cell function. Hence, ARG inhibition can reverse immunosuppression enhancing antitumor immunity. We describe AZD0011, a novel peptidic boronic acid prodrug to deliver an orally available, highly potent, ARG inhibitor payload (AZD0011-PL). We demonstrate that AZD0011-PL is unable to permeate cells, suggesting that this compound will only inhibit extracellular ARG. In vivo, AZD0011 monotherapy leads to arginine increases, immune cell activation, and tumor growth inhibition in various syngeneic models. Antitumor responses increase when AZD0011 is combined with anti–PD-L1 treatment, correlating with increases in multiple tumor immune cell populations. We demonstrate a novel triple combination of AZD0011, anti–PD-L1, and anti-NKG2A, and combination benefits with type I IFN inducers, including polyI:C and radiotherapy. Our preclinical data demonstrate AZD0011’s ability to reverse tumor immunosuppression and enhance immune stimulation and antitumor responses with diverse combination partners providing potential strategies to increase immuno-oncology therapies clinically.

While family engagement at the individual level of health care, such as families partnering with providers in decision-making about health care for an individual child has been well studied, family engagement in systems-level activities (e.g., participation in advisory and other decision-making groups, or creation and revision of policies) that impact the health services families and children receive has not. This note from the field presents a framework that describes the information and supports that help families partner with professionals and contribute to systems-level activities. Without attention to these components of family engagement, family presence and participation may be only token. We engaged an expert Family/Professional Workgroup whose members represented key constituencies and diverse geography, race/ethnicity, and areas of expertise; conducted a review of peer-reviewed publications and grey literature; and conducted a series of key informant interviews to identify best practices for supporting meaningful family engagement at the systems level. Based on an analysis of the findings, the authors identified four action-oriented domains of family engagement and key criteria that support and strengthen meaningful family engagement in systems-level initiatives. Child- and family-serving serving organizations can use this Family Engagement in Systems framework to support meaningful family engagement in the design of policies, practices, services, supports, quality improvement projects, research, and other systems-level activities.

Neonicotinoid insecticides are used to manage spotted lanternfly (Lycorma delicatula (White); hereafter SLF), a recently introduced pest in the United States. Neonicotinoids can harm nontargets, such as pollinators potentially exposed via floral resources of treated plants. We quantified neonicotinoid residues in whole flowers of two SLF host plant species, red maple (Acer rubrum L. [Sapindales: Sapindaceae]) and tree-of-heaven (Ailanthus altissima (Mill.) [Sapindales: Simaroubaceae]), treated with post-bloom imidacloprid or dinotefuran applications that differed in timing and method of application. In red maple flowers, dinotefuran residues from fall applications were significantly higher than summer applications, while imidacloprid residues from fall applications were significantly lower than summer applications. Residues did not differ between application methods or sites. In tree-of-heaven flowers, dinotefuran residues were only detected in one of 28 samples at a very low concentration. To assess acute mortality risk to bees from oral exposure to residues in these flowers, we calculated risk quotients (RQ) using mean and 95% prediction interval residue concentrations from treatments in this study and lethal concentrations obtained from acute oral bioassays for Apis mellifera (L. (Hymenoptera: Apidae)) and Osmia cornifrons (Radoszkowski (Hymenoptera: Megachilidae)), then compared these RQs to a level of concern. For A. mellifera, only one treatment group, applied at 2X maximum label rate, had an RQ that exceeded this level. However, several RQs for O. cornifrons exceeded the level of concern, suggesting potential acute risk to solitary bees. Further studies are recommended for more comprehensive risk assessments to nontargets from neonicotinoid use for SLF management.

Background From 2015 to 2020, the Centers for Disease Control and Prevention’s Colorectal Cancer Control Program (CRCCP) supported 30 awardees in partnering with primary care clinics to implement evidence-based interventions (EBIs) and supporting activities (SAs) to increase colorectal cancer (CRC) screening. This study identified factors that facilitated early implementation and sustainability within partner clinics. Methods We conducted longitudinal qualitative case studies of four CRCCP awardees and four of their partner clinics. We used the Consolidated Framework for Implementation Research (CFIR) to frame understanding of factors related to implementation and sustainability. A total of 41 semi-structured interviews were conducted with key staff and stakeholders exploring implementation practices and facilitators to sustainability. Qualitative thematic analysis of interview transcripts identified emerging themes across awardees and clinics. Results Qualitative themes related to six CFIR inner setting constructs—structural characteristics, readiness for implementation, networks and communication, culture, and implementation climate—were identified. Themes related to early implementation included conducting readiness assessments to tailor implementation, providing moderate funding to clinics, identifying clinic champions, and coordinating EBIs and SAs with existing clinic practices. Themes related to sustainability included the importance of ongoing electronic health record (EHR) support, clinic leadership support, team-based care, and EBI and SA integration with clinic policies, workflows, and procedures. Implications Findings help to inform future scale-up of and decision-making within CRC screening programs and other chronic disease prevention programs implementing EBIs and SAs within primary care clinics and also highlight factors that maximize sustainability within these programs.

PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Five-year survival is approaching 90%. In efforts to further improve outcomes, it is critical to consider the cost of ALL care. MATERIALS AND METHODS: Commercial insurance data from OptumLabs Data Warehouse were used to identify patients with ALL, age 1-30 years, diagnosed in 1993-2017 in the United States, with 36 months of continuous insurance coverage. Patients treated with hematopoietic cell transplantation were excluded. Inpatient and outpatient utilization and cumulative reimbursements (inflation-adjusted to December 2020) were computed 8 and 36 months from diagnosis and stratified by age (1-9, 10-12, and ≥ 13 years) as proxies for National Cancer Institute risk groups. Regression models were constructed to assess associations with demographic and clinical characteristics. RESULTS: Among 927 patients (median age, 6 years; interquartile range, 3-12 years; 43% female), individuals age ≥ 10 years had 23-25 more inpatient days and 22 more outpatient encounters compared with younger patients. The 36-month median cost was $394,000 (USD) (interquartile range, $256,000-$695,000 [USD]), and 64% of the total cost was incurred during the initial 8 months. The 36-month cost was 1.5-fold higher for those age 10-12 years and 1.7-fold higher for those age ≥ 13 years compared with 1-9 years. The cost for those diagnosed in 2013-2017 was 70% higher compared with 1993-2002, and was not different on the basis of sex, race, or ethnicity. CONCLUSION: Older age was associated with higher utilization and cost, and the cost of treatment increased significantly over time. These data provide valuable benchmarks for future studies examining the cost-benefit of ALL therapy modifications.

Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy ( P = 0.69) and HIV status ( P = 0.53) were not.Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes.

Purpose: Untreated hearing loss is a significant public health issue affecting the quality of life of millions of Americans. Barriers to treatment invite novel and innovation solutions, but as these solutions create new treatment delivery models, they also may—purposefully or accidentally—challenge the values of the field. Method: Value-sensitive design methodology is used in this study to identify the values in current hearing health care service delivery. We performed qualitative content analysis of questionnaires, clinical practice guidelines, and professional ethics documents that represent the intended and enacted values in audiology. Results: The result is a comprehensive list of values that can be used as a structured codebook for systematic textual analysis of materials representing current best practices in the provision of hearing health care services. A secondary result is an analysis of the relative importance of values in audiology, inferred from the frequency of references to each value. Conclusions: Subjective benefit, professional duties, and self-efficacy were the core values identified in the current provision of audiologic care, and these values should be central to considerations for new hearing health care models and technologies.

Se realizó un estudio bajo un diagnóstico del diseño de la infraestructura y la prestación del servicio educativo, que requiere de atención para reducir las brechas existentes en las instituciones educativas públicas. En el estudio se consideró el objetivo de establecer la incidencia de la percepción del diseño de la infraestructura en la prestación del servicio educativo de las instituciones educativas públicas. El enfoque de investigación se circunscribe en un enfoque cuantitativo, diseño no experimental y de alcance correlacional causal. La población estuvo determinada por 541 docentes de 14 instituciones educativas y mediante muestreo probabilístico se obtuvo una muestra de 225 docentes, representantes de las 14 instituciones educativas. Se aplicaron dos cuestionarios de la percepción del diseño de la infraestructura en la prestación del servicio educativo, contemplando que el Pseudo R2 de Nagelkerke fue de 0.593 y se establece que el diseño de la infraestructura educativa incide en 59.3% en las condiciones el servicio educativo; así mismo la dimensión optimización del diseño de infraestructura predice mejor el servicio educativo, debido a Wald= 10.115 y p= 0.001 y concluyó que existe incidencia significativa del diseño de infraestructura educativa en las condiciones del servicio educativo de las instituciones educativas públicas.

Sympathetic efferent axons regulate cardiac functions. However, the topographical distribution and morphology of cardiac sympathetic efferent axons remain insufficiently characterized due to the technical challenges involved in immunohistochemical labeling of the thick walls of the whole heart. In this study, flat-mounts of the left and right atria and ventricles of FVB mice were immunolabeled for tyrosine hydroxylase (TH), a marker of sympathetic nerves. Atrial and ventricular flat-mounts were scanned using a confocal microscope to construct montages. We found (1) In the atria: A few large TH-immunoreactive (IR) axon bundles entered both atria, branched into small bundles and then single axons that eventually formed very dense terminal networks in the epicardium, myocardium and inlet regions of great vessels to the atria. Varicose TH-IR axons formed close contact with cardiomyocytes, vessels, and adipocytes. Multiple intrinsic cardiac ganglia (ICG) were identified in the epicardium of both atria, and a subpopulation of the neurons in the ICG were TH-IR. Most TH-IR axons in bundles traveled through ICG before forming dense varicose terminal networks in cardiomyocytes. We did not observe varicose TH-IR terminals encircling ICG neurons. (2) In the left and right ventricles and interventricular septum: TH-IR axons formed dense terminal networks in the epicardium, myocardium, and vasculature. Collectively, TH labeling is achievable in flat-mounts of thick cardiac walls, enabling detailed mapping of catecholaminergic axons and terminal structures in the whole heart at single-cell/axon/varicosity scale. This approach provides a foundation for future quantification of the topographical organization of the cardiac sympathetic innervation in different pathological conditions.

In order to create a more diverse workforce, there is a need to involve historically excluded youth in public health-related work. Youth involvement in asset-based work experience approaches is especially relevant for rural areas with workforce shortages.To explore the public health workforce development implications of community-based career exploration and asset mapping work experience from the perspective of Black youth.We used qualitative in-depth interviews with youth, aged 14 to 22 years, who participated in a work experience program anchored in several rural counties in southeastern United States. A phenomenological lens was applied for qualitative analyses with iterative, team-based data coding. Participants were also surveyed pre- and postprogram to supplement findings.A rural community-based organization's work experience program consisted of 2 tracks: (1) Youth Connect-a career exploration track that included work placement within community agencies; and (2) MAPSCorps-a track that employs youth to conduct asset mapping for their community.We interviewed 28 of 31 total participants in the 2 tracks. We uncovered 4 emergent profiles in how youth described shifts in their perceptions of community: (1) Skill Developers; (2) Community Questioners; (3) Community Observers; and (4) Community Enthusiasts. In comparing between tracks, youth who participated in work experience that involved asset mapping uniquely described increased observation and expanded view of community resources and had greater increases in research self-efficacy than youth who participated only in career exploration.Asset mapping work experience that is directly placed in rural communities can expose Black youth to and engage them in essential public health services (assessing and mobilizing community assets) that impact their community. This type of program, directly integrated into rural communities rather than placed near academic centers, could play a role in creating a more diverse public health workforce.

Introducción. Los pacientes con Covid-19 tienen el riesgo de presentar síndrome de dificultad respiratoria aguda, por lo que pueden requerir ventilación mecánica y traqueostomía. De este modo, la decanulación es un proceso importante que está a cargo del equipo rehabilitador. Objetivos. Describir y caracterizar el proceso de decanulación en pacientes traqueostomizados con COVID-19 para identificar posibles factores que influyen en su realización exitosa. Métodos. Estudio descriptivo transversal realizado en los pacientes que fueron sometidos a traqueostomía entre junio de 2020 y julio del 2021 en la Clínica de Alta Complejidad Santa Bárbara de Palmira, Colombia. Las variables categóricas se presentaron con porcentajes y para las cuantitativas se contrastó la hipótesis de normalidad a través de la prueba de Kolmogorov-Smirnov. Resultados. Los pacientes, al momento de ingreso, tenían características de severidad, con un promedio de PaO2/FiO2 de 99,7 mmhg y bloqueo neuromuscular hasta por 20 días; el tiempo promedio de ventilación mecánica fue 17,3 días. A todos los pacientes el equipo de rehabilitación les realizó intervención; de los 15 pacientes incluidos, tres no fueron decanulados. Se realizó un análisis descriptivo de los objetivos y de la interven- ción realizada por cada disciplina; para los tres pacientes no decanulados se analizaron las principales barreras y los predictores del fracaso de una decanulación. Conclusión. Gracias a la instauración de un plan constante y activo de rehabilitación multidisciplinario en el que los pacientes reciben intervención desde su ingreso hasta su egreso se logró decanular de manera exitosa al 80% de los pacientes traqueostomizados.

Previous reports comparing transcarotid (TC) versus transfemoral (TF) approaches for patients undergoing transcatheter aortic valve replacement have had inconsistent conclusions. We compared in-hospital and 1-year clinical outcomes, changes in quality of life, and direct hospital costs for 138 TC versus 1,926 TF procedures. Propensity matching based on the Society of Thoracic Surgery Predicted Risk of Mortality was used to compare 130 patients who underwent TC with 813 patients who underwent TF. Matched TC versus TF cohorts did not differ with respect to in-hospital mortality (0.0% vs 1.4%, p = 0.380), stroke (2.3% vs 2.5%, p = 0.917), major vascular complications (0.8% vs 2.2%, p = 0.268), composite bleeding complications (4.6% vs 6.4%, p = 0.647), requirement for permanent pacemaker (14.6% vs 12.9%, p = 0.426), postoperative hospital length of stay (3.3 ± 3.4 vs 3.1 ± 3.3 days, p = 0.467), or direct hospital costs ($52,899 ± 9,560 vs $50,464 ± 10,997, p = 0.230). Similarly, at 1-year, patients who underwent TC versus patients who underwent TF did not differ with respect to all-cause mortality (7.6% vs 6.4%, p = 0.659), hospital readmission (20.0% vs 23.9%, p = 0.635), or quality of life as measured by the Kansas City Cardiomyopathy Questionnaire score (84.0 ± 17.1 vs 88.4 ± 13.9, p = 0.062). Patients who underwent TC and TF did not differ with respect to in-hospital complications, length of hospital stay, and direct hospital costs, as well as 1-year mortality, readmission, and quality of life. These data add to ongoing support for the TC approach as the optimal alternative access for patients with transcatheter aortic valve replacement deferred from a transfemoral approach.

Differential screening is a complex process in chronic pain conditions. There is significant uncertainty that surrounds the pathophysiology of many chronic pain syndromes that may lead to misdiagnosis and treatment failures. Such differential screening is even more challenging where there is regional overlapping from surrounding tissues. This case report chronicles the differential screening and treatment of a patient with sternocleidomastoid syndrome (SCMS) originally diagnosed as Eagle's syndrome (ES).A 55-year-old woman, referred to a physical therapist (PT) by an ear, nose and throat (ENT) physician with the diagnosis of ES. The patient complained of yearlong left-sided otalgia, blurred vision, excessive lacrimation, dysphagia, hyperesthesia on the left side of the face, unilateral temporal headaches, and both left mandibular and anterior neck pain.The PT examination revealed the patient did not exhibit hallmark findings for clinical confirmation of ES and instead demonstrated multiple signs consistent with SCMS.Manual therapy techniques and therapeutic exercises resolved the patient's year-long chronic symptoms within 6 sessions.

Hypertension is characterized by increased sodium (Na+) reabsorption along the aldosterone-sensitive distal nephron (ASDN) as well as chronic systemic inflammation. Interleukin-6 (IL-6) is thought to be a mediator of this inflammatory process. Interestingly, increased Na+ reabsorption within the ASDN does not always correlate with increases in aldosterone (Aldo), the primary hormone that modulates Na+ reabsorption via the mineralocorticoid receptor (MR). Thus, understanding how increased ASDN Na+ reabsorption may occur independent of Aldo stimulation is critical. Here, we show that IL-6 can activate the MR by activating Rac1 and stimulating the generation of reactive oxygen species (ROS) with a consequent increase in thiazide-sensitive Na+ uptake. Using an in vitro model of the distal convoluted tubule (DCT2), mDCT15 cells, we observed nuclear translocation of eGFP-tagged MR after IL-6 treatment. To confirm the activation of downstream transcription factors, mDCT15 cells were transfected with mineralocorticoid response element (MRE)-luciferase reporter constructs; then treated with vehicle, Aldo, or IL-6. Aldosterone or IL-6 treatment increased luciferase activity that was reversed with MR antagonist cotreatment, but IL-6 treatment was reversed by Rac1 inhibition or ROS reduction. In both mDCT15 and mpkCCD cells, IL-6 increased amiloride-sensitive transepithelial Na+ current. ROS and IL-6 increased 22Na+ uptake via the thiazide-sensitive sodium chloride cotransporter (NCC). These results are the first to demonstrate that IL-6 can activate the MR resulting in MRE activation and that IL-6 increases NCC-mediated Na+ reabsorption, providing evidence for an alternative mechanism for stimulating ASDN Na+ uptake during conditions where Aldo-mediated MR stimulation may not occur.

Zeta is a relatively recently developed tool for authorship attribution and computational stylistics (Craig and Kinney, 2009, Shakespeare, Computers, and the Mystery of Authorship. Cambridge: Cambridge University Press). In ‘The Interpretation of Zeta Test Results’ (2019), Perves Rizvi raised several objections to the method. I responded to and rejected those objections in ‘Zeta Revisited’ (Hoover, 2021a, Zeta revisited. Digital Scholarship in the Humanities, 1–20). Rizvi has renewed two of his main objections in a critique of my response in his ‘The Interpretation of Zeta Test Results: A Supplement’ (2022). First, he reiterates and expands his argument that the separation of base and counter segments in a Zeta analysis is a mechanical consequence of Zeta, rather than a significant and meaningful finding. Second, he again rejects the use of the bisector line to attribute texts in a Zeta analysis as unsound and adds new arguments that it leads to invalid attributions. This rejoinder provides further evidence and argument that both of Rizvi’s claims must be rejected.