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Respiratory syncytial virus (RSV) causes a significant burden of acute respiratory illness across all ages, particularly for infants and older adults. Infants, especially those born prematurely or with underlying health conditions, face a high risk of severe RSV-related lower respiratory tract infections (LRTIs). Globally, RSV contributes to millions of LRTI cases annually, with a disproportionate burden in low- and middle-income countries (LMICs). The RSV virion outer capsule contains glycoproteins G and F which are essential for viral entry into respiratory epithelial cells and represent key targets for therapeutics development. The F-glycoprotein has several highly conserved antigenic sites that have proven useful targets for the development of monoclonal antibodies (mAbs) against RSV. Historically, prevention in infants was limited to the mAb palivizumab, which, despite its efficacy, was costly and inaccessible in many regions. Recent advancements include nirsevimab, a long-acting mAb that has shown substantial efficacy in reducing medically attended RSV-related disease in infants, in phase III clinical trials, early regional and national real-world data. In addition, three new vaccines have been approved: two protein subunit vaccines and a messenger RNA vaccine. The vaccines are all licenced for use in older adults, with one also approved as a maternal vaccine. Promising candidates in development include the mAb clesrovimab, which has an extended half-life and high levels in the nasal epithelial lining and high safety and efficacy profiles in late-stage trials. There are also a wide range of vaccine candidates currently in late-stage clinical trials. These developments signify a major advancement in RSV prevention strategies, offering improved protection for high-risk populations. With the ongoing rollout of the recently licenced vaccines and mAbs internationally, the landscape of RSV care is rapidly changing. We also must ensure these advances reach those in LMICs who need these therapies most., (© The Author(s), 2025.)

Objective: To examine the association between caregiver-report of their child's inadequate sleep and exposure to interpersonal racism within racially minoritized subpopulations., Study Design: We conducted cross-sectional analysis among racially minoritized 21 924 school-aged children and 27 142 adolescents using a National Survey of Children's Health sample from 2016 through 2021. Multivariable logistic regression models were fit to estimate predicted probabilities for the adjusted associations between caregiver-report of their child's inadequate sleep and prior exposure to interpersonal racism., Results: In bivariate models, caregiver report of child exposure to interpersonal racism was significantly associated with a higher probability of inadequate sleep within non-Hispanic Asian American/Pacific Islander school-aged children, Hispanic adolescents, and non-Hispanic multiracial adolescents. After adjusting for covariates, only the association within Hispanic youth remained significant though attenuated. Unexpectedly, non-Hispanic Black school-age children exposed to racism had a lower probability of inadequate sleep than non-Hispanic Black children without exposure to racism after adjusting for covariates., Conclusions: Nationally representative pooled data that showed caregiver-report of Hispanic adolescents' inadequate sleep was associated with their exposure to interpersonal racism, although an association with inadequate sleep was not found in other racially minoritized subpopulations. Examining within-race associations helps to assess more accurately risk and target efforts that seek to address racism-related stress among racially minoritized subpopulations., Competing Interests: Declaration of Competing Interest At the time of this study, M.A.D.’s time was funded by the National Heart, Lung, Blood Institute (NHLBI) award number: 1K01HL169493-01.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Supporting psychological well-being in persons with aphasia (PWA) can improve social and health outcomes; however, PWA and their care partners (CPs) are often not receiving mental health support. Previous research explores this from the perspective of health care professionals., Aims: The aim of this study was to examine knowledge, beliefs, and experiences related to mental health services directly from PWA and CPs., Method: The study included 11 PWA and 11 CPs. Participants completed a guided survey (virtual) with opportunities for elaboration related to the knowledge, beliefs, and experiences of mental health., Results: There was variability in personal preferences for referrals, types of coping strategies, and confidants for general thoughts and feelings and those specific to aphasia. PWA identified health care professionals as people to share thoughts and feelings, whereas CPs chose family and friends more often. Both CPs and PWA reported communication difficulty and finding a counselor as "sometimes" preventing access to services but cited fear and trust as "always" preventing access., Conclusions: Knowledge, beliefs, and experience with help-seeking and mental health services are personal and variable. Assessing barriers unique to living with aphasia, such as communication challenges and locating a suitable counselor, must also be considered within more complex and personal barriers of fear and trust that are consistently reported in the general public. Health professionals across the continuum of aphasia care need to understand the communication challenges of living with aphasia in tandem with understanding individual differences to personalize approaches to mental health services and help-seeking.

Purpose: To conduct an integrative review of extant literature on prison nursery programs in the United States., Background: About 4-10% of U.S. women entering prison are pregnant. In response, several state prisons have developed nurseries to promote maternal-infant outcomes and reduce recidivism. Unfortunately, little is known about the current state of the science related to prison nurseries., Methods: Guided by Whittemore and Knafl's methodology, a literature search was conducted in June 2023 for peer-reviewed articles using PubMed, CINAHL, MedLINE, SCOPUS, PsycINFO, socINDEX, and Academic Search Complete. Broad keywords were used ("prison" or "incarceration" or "inmate") and ("nursery" or "nursery residential center"). Included articles were U.S.-based, peer-reviewed, and specific to prison nurseries., Results: The search yielded 216 articles, 10 of which were included for final review and synthesis. Using the Johns Hopkins Evidence Level and Quality Guide, the level of evidence ranged from low to moderate. Themes include (1) benefits to maternal-child attachment and bonding, (2) institutional barriers and challenges to maternal-child attachment and bonding and (3) beneficial maternal justice and custodial outcomes., Conclusions: Prison nurseries are a promising intervention to promote mother-infant outcomes. These programs promote positive maternal-infant attachment and bonding, help mothers maintain custody of their children, and reduce recidivism., Implications for Practice: There is a need to standardize nursery program characteristics to maximize benefits and promote equity. Better investment in longitudinal, quasi-experimental, and qualitative research is needed., Competing Interests: The authors declare no conflicts of interest. There are no sources of funding for this work., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mothers experiencing homelessness and caring for young children struggle with high rates of substance use and mental health problems. A comprehensive supportive housing intervention was implemented to assist young mothers experiencing substance use disorder (SUD) and homelessness. The cost-effectiveness of this intensive intervention could inform future dissemination., Methods: A cost-effectiveness analysis was conducted alongside a randomized controlled trial that lasted from May 2015 to October 2018. Mothers experiencing homelessness between the ages of 18-24 years with a SUD were randomly assigned to housing+support services (HOU + SS) (n = 80), housing-only (HOU) (n = 80), or services as usual SAU (n = 80). Using incremental cost-effectiveness ratios (ICERs), the study compared the costs of HOU + SS and HOU to SAU for three outcomes: housing stability (percent days of stable housing), substance use (percent days of substance use), and depressive symptoms (Beck Depression Inventory score). Direct intervention costs of HOU + SS and HOU from both payor and societal perspectives were estimated. Cost data were collected from detailed study financial records. Outcomes were taken from 6-month assessments., Results: The average societal cost of HOU + SS per participant was $5114 [CI 95 %, $4949-5278], while the average societal cost of HOU was $3248 [CI 95 %, $ 3,140-$3341] (2019 U.S. dollars). The calculated ICERs show that HOU was more cost-effective than HOU + SS and SAU for housing outcome. For illicit drug use, HOU + SS was more cost-effective than HOU. Finally, for depressive symptoms, neither HOU + SS or HOU were more cost effective than SAU., Conclusion: While HOU is more cost-effective for increasing housing, HOU + SS is more cost-effective for reducing illicit drug use. However, housing without improvements in substance use may not be sustainable, and supportive services are likely essential for improved well-being overall beyond the housing outcome alone., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: While research on substance using youth experiencing homelessness (YEH) is increasing, there is a dearth of information regarding effective prevention interventions for these youth. Suicide is the leading cause of death among YEH and most youth do not access services that may be available to them. Therefore, this study seeks to address this gap in the research literature with the goal to identify an effective suicide prevention intervention that can be readily adopted by communities that serve these youth., Methods: Three hundred (N = 300) YEH with recent substance use and suicidal ideation or a recent suicide attempt will be recruited from the streets as well as a drop-in center serving YEH. After the baseline assessment, all youth will be randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP) + Services as Usual (SAU) (N = 150) or to SAU alone (N = 150). SAU includes outreach, advocacy, and service linkage whereas YEH who receive CTSP will also receive ten CTSP sessions and an optional nine booster sessions. Follow-up assessments will be conducted at 3, 6, 9, and 12 months post-baseline. Theoretically derived mediators (e.g., cognitive distortions) will be tested to shed light on mechanisms associated with change, and the moderating effects of sex, race, sexual orientation, and baseline service connection will be examined. In order to ease future dissemination of the intervention to agencies serving YEH, we will rigorously assess acceptability, feasibility, fidelity, and cost associated with the delivery of our intervention approach using a mixed-methods approach., Discussion: This study adds to a very small number of clinical trials seeking to prevent lethal suicide among a very high-risk group by addressing suicidal ideation directly rather than underlying conditions. It is hypothesized that youth receiving CTSP + SAU will show greater reductions in suicidal ideation (primary outcome), substance use, and depressive symptoms (secondary outcomes) over time compared to SAU alone, as well as improved risk and protective factors., Trial Registration: NCT05994612. Date of Registration: August 16, 2023., (© 2024. The Author(s).)

Introduction: Our objective was to perform a feasibility study using real-world data from a learning health system (LHS) to describe current practice patterns of wound closure and explore differences in outcomes associated with the use of tissue adhesives and other methods of wound closure in the pediatric surgical population to inform a potentially large study., Methods: A multi-institutional cross-sectional study was performed of a random sample of patients <18 y-old who underwent laparoscopic appendectomy, open or laparoscopic inguinal hernia repair, umbilical hernia repair, or repair of traumatic laceration from January 1, 2019, to December 31, 2019. Sociodemographic and operative characteristics were obtained from 6 PEDSnet (a national pediatric LHS) children's hospitals and OneFlorida Clinical Research Consortium (a PCORnet collaboration across 14 academic health systems). Additional clinical data elements were collected via chart review., Results: Of the 692 patients included, 182 (26.3%) had appendectomies, 155 (22.4%) inguinal hernia repairs, 163 (23.6%) umbilical hernia repairs, and 192 (27.8%) traumatic lacerations. Of the 500 surgical incisions, sutures with tissue adhesives were the most frequently used (n = 211, 42.2%), followed by sutures with adhesive strips (n = 176, 35.2%), and sutures only (n = 72, 14.4%). Most traumatic lacerations were repaired with sutures only (n = 127, 64.5%). The overall wound-related complication rate was 3.0% and resumption of normal activities was recommended at a median of 14 d (interquartile ranges 14-14)., Conclusions: The LHS represents an efficient tool to identify cohorts of pediatric surgical patients to perform comparative effectiveness research using real-world data to support medical and surgical products/devices in children., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Community-level disinvestment and de facto segregation rooted in decades of discriminatory race-based policies and racism have resulted in unacceptably large infant mortality rates in racial minority neighborhoods across the US. Most community development and housing work, implemented with the goal of addressing health and social inequities, is designed to tackle current challenges in the condition of neighborhoods without a race-conscious lens assessing structural racism and discrimination. Using one historically segregated neighborhood-Linden, in Columbus, Ohio-we detail how state and local policies have affected the neighborhood and shaped neighborhood-level demographics and resources during the past 100 years. We explore how structural racism- and discrimination-informed strategic community reinvestment could provide a solution and yield lasting change.

Little is known about clinical documentation for youth exposed to parental justiceinvolvement (e.g., parole, probation, jail, prison). We reviewed the electronic health records of 100 youth with at least one mention of parental incarceration between 2011-2019 from a large Midwestern pediatric hospital-based institution to describe clinical documentation and health characteristics. Within the sample, youth more commonly experienced incarceration of a father-identified figure (68%) as opposed to a mother-identified figure (32%). Seventeen percent (17%) of the youth were between zero and four years of age when clinicians documented exposure to a parent's incarceration. Nearly one-third of youth charts had no documentation regarding service referrals or follow-up from providers upon disclosure of parental incarceration. Few clinician documentation details were present related to the context of parental justice involvement (timing, type, and duration). Future research is needed to better understand the intersection of parental justice involvement and child health and service connection.

Abstract: National nursing organizations have called for nurses to provide leadership in care solutions for high-cost/high-needs vulnerable populations. In response to this call, important modifications are emerging in Doctor of Nursing Practice programs, including an increasing number of nurses pursuing dual certification in primary care and psychiatric mental health or primary care nurse practitioners returning for a postgraduate certificate in psychiatric mental health. This innovative role warrants examination, particularly because it relates to high-needs/high-cost patients such as those with serious mental illness (SMI). This article highlights two aspects of the role of the primary care/psychiatric mental health nurse practitioner (PC/PMHNP): one, to provide a vision of the PC/PMHNP as a unique solution for optimal care of vulnerable patients and two, to demonstrate potential contributions of the PC/PMHNP to the larger health care system. A case exemplar is used to illustrate role contributions of the PC/PMHNP in a high-needs/high-cost patient with SMI and complex co-occurring physical illness. Three capacities of the PC/PMHNP are discussed: depth and breath, expert engagement and rapport building, and full patient-centered care and flexibility. The case exemplar emphasizes the PC/PMHNP value through transitions across care settings and where gaps in service frequently occur. The impact of the PC/PMHNP on improved patient outcomes, patient and provider satisfaction, and cost savings are explored., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2023 American Association of Nurse Practitioners.)

Youth involved in the legal system (YILS) experience rates of opioid and substance use disorders (OUD/SUDs) and overdose that is well above those in the general population. Despite the dire need, and the existing programs that focus on treatment of these problems in YILS, research on opioid initiation, and OUD prevention, including feasibility and sustainability, are severely limited. We present four studies testing interventions that, while not necessarily novel as SUD treatments, test novel structural and interpersonal strategies to prevent opioid initiation/OUD precursors: (1) ADAPT (Clinical Trial No. NCT04499079) provides real-time feedback using community-based treatment information system data to create a more effective mental health and SUD treatment cascade to prevent opioid use; (2) HOME (Clinical Trial No. NCT04135703) provides youth experiencing homelessness, including YILS, with direct access to shelter in independent living without prerequisites as an opioid initiation prevention strategy; (3) LeSA (Clinical Trial No. NCT04678960) uses the Trust-Based Relational Intervention ® to equip YILS and their caregivers with self-regulatory and communication skills during the transition from secure confinement to reduce opioid initiation/re-initiation; and (4) POST (Clinical Trial No. NCT04901312) tests two interventions integrating interpersonal/drinking and drug refusal skills, case management, and goal setting among YILS in transitioning out of secure detention as opioid initiation prevention strategies. We discuss early implementation barriers and facilitators, including complexities of prevention research with YILS and adaptations due to COVID-19. We conclude by describing anticipated end products, including implementation of effective prevention interventions and integration of data from multiple projects to address larger, multi-site research questions., (© 2023. Society for Prevention Research.)

We aim to review the association between childhood-onset mental health conditions and increased risk for early substance use including opioid misuse and opioid use disorders (OUD). The association between mental health conditions and opioid misuse suggests youth with mental health conditions may benefit from opioid prevention efforts that concurrently address mental health. To aid in the identification of youth with mental health conditions who could benefit from interventions, we will review opportunities and challenges associated with screening for mental health symptoms or substance use in settings where youth at high risk for mental health conditions present. We will also review how research projects within the National Institutes of Health's Helping to End Addiction Long-term (HEAL) Prevention Cooperative are addressing mental health within opioid misuse and OUD prevention interventions for youth., (© 2023. Society for Prevention Research.)

Background: Youth, 18 to 24 years, experiencing homelessness (YEH) are recognized as having developmental challenges dissimilar to older adults. Yet, research on efforts to end homelessness and prevent or intervene in drug use and mental health problems among youth have lagged behind that of adults. The Housing First (HF) Model which underlies Permanent Supportive Housing (PSH) and Rapid Re-Housing (RRH) has become preferred over treatment-first models., Methods and Results: We provide an overview of PSH and RRH studies to date and summarize our current understanding of their utility for use with YEH. Finally, we review our team's current and past randomized trials testing RRH with YEH, providing lessons learned and recommendations., Conclusion: Current research efforts to guide best practices are hampered by a lack of fidelity to HF principles, lack of randomized design, and lack of focus on youth. Lessons learned and recommendations from our work are offered to facilitate the future work of those who seek to end homelessness and address drug use and mental health problems among youth., (© 2023. Evans Medical Foundation, Inc. and BioMed Central Ltd.)

Background: Electronic health records (EHRs) data provide an opportunity to collect patient information rapidly, efficiently and at scale. National collaborative research networks, such as PEDSnet, aggregate EHRs data across institutions, enabling rapid identification of pediatric disease cohorts and generating new knowledge for medical conditions. To date, aggregation of EHR data has had limited applications in advancing our understanding of mental health (MH) conditions, in part due to the limited research in clinical informatics, necessary for the translation of EHR data to child mental health research., Methods: In this cohort study, a comprehensive EHR-based typology was developed by an interdisciplinary team, with expertise in informatics and child and adolescent psychiatry, to query aggregated, standardized EHR data for the full spectrum of MH conditions (disorders/symptoms and exposure to adverse childhood experiences (ACEs), across 13 years (2010-2023), from 9 PEDSnet centers. Patients with and without MH disorders/symptoms (without ACEs), were compared by age, gender, race/ethnicity, insurance, and chronic physical conditions. Patients with ACEs alone were compared with those that also had MH disorders/symptoms. Prevalence estimates for patients with 1 + disorder/symptoms and for specific disorders/symptoms and exposure to ACEs were calculated, as well as risk for developing MH disorder/symptoms., Results: The EHR study data set included 7,852,081 patients < 21 years of age, of which 52.1% were male. Of this group, 1,552,726 (19.8%), without exposure to ACEs, had a lifetime MH disorders/symptoms, 56.5% being male. Annual prevalence estimates of MH disorders/symptoms (without exposure to ACEs) rose from 10.6% to 2010 to 15.1% in 2023, a 44% relative increase, peaking to 15.4% in 2019, prior to the Covid-19 pandemic. MH categories with the largest increases between 2010 and 2023 were exposure to ACEs (1.7, 95% CI 1.6-1.8), anxiety disorders (2.8, 95% CI 2.8-2.9), eating/feeding disorders (2.1, 95% CI 2.1-2.2), gender dysphoria/sexual dysfunction (43.6, 95% CI 35.8-53.0), and intentional self-harm/suicidality (3.3, 95% CI 3.2-3.5). White youths had the highest rates in most categories, except for disruptive behavior disorders, elimination disorders, psychotic disorders, and standalone symptoms which Black youths had higher rates. Median age of detection was 8.1 years (IQR 3.5-13.5) with all standalone symptoms recorded earlier than the corresponding MH disorder categories., Conclusions: These results support EHRs' capability in capturing the full spectrum of MH disorders/symptoms and exposure to ACEs, identifying the proportion of patients and groups at risk, and detecting trends throughout a 13-year period that included the Covid-19 pandemic. Standardized EHR data, which capture MH conditions is critical for health systems to examine past and current trends for future surveillance. Our publicly available EHR-mental health typology codes can be used in other studies to further advance research in this area., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Investigations of chronic physiological stress measured by hair cortisol are rapidly expanding among community samples of adolescents and adults. However, research examining physiological stress among youth experiencing homelessness is nascent despite the youth's increased risk for adverse exposures and subsequent impaired mental health., Objective: This article aimed to examine the feasibility of collecting hair for measuring cortisol among diverse youth experiencing homelessness and gain an understanding of variation in participation., Methods: Analysis of survey and hair participation data from three pilot studies among youth experiencing homelessness was conducted. Survey measures included sociodemographic characteristics (age, race and ethnicity, sex assigned at birth, and sexual orientation) and reasons for nonparticipation. Descriptive analysis examined participation rates in hair collection for cortisol measurement, including sociodemographic differences in participation., Results: Participation in the hair sampling for cortisol was high for the combined sample (88.4%), with some variation across the three pilot studies. Insufficient hair for cutting was the most common reason for not participating; Black and multiracial youth, as well as male youth, had a higher prevalence of nonparticipation., Discussion: The collection of hair for cortisol research among youth experiencing homelessness is feasible, and integration of physiological measures of stress into research with this vulnerable population should be considered, given their high risk for adversity and death by suicide and drug overdose. Methodological considerations and avenues for potential research are discussed., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Anxiety disorder diagnoses in office-based settings increased for children through the mid-2010s, but recent changes in diagnosis and treatment are not well understood. The objectives of the current study were to evaluate recent trends in anxiety disorder diagnosis and treatment among children, adolescents, and young adults., Methods: This study used serial cross-sectional data from the National Ambulatory Medical Care Survey (2006-2018), a nationally representative annual survey of US office-based visits. Changes in anxiety disorder diagnosis and 4 treatment categories (therapy alone, therapy and medications, medications alone, or neither) are described across 3 periods (2006-2009, 2010-2013, 2014-2018). Multinomial logistic regression compared differences in treatment categories, adjusting for age group, sex, and race/ethnicity, contrasting the last and middle periods with the first., Results: The overall proportion of office visits with an anxiety disorder diagnosis significantly increased from 1.4% (95% confidence interval [CI] 1.2-1.7; n = 9 246 921 visits) in 2006 to 2009 to 4.2% (95% CI 3.4-5.2; n = 23 120 958 visits) in 2014 to 2018. The proportion of visits with any therapy decreased from 48.8% (95% CI 40.1-57.6) to 32.6% (95% CI 24.5-41.8), but there was no significant change in the overall use of medications. The likelihood of receiving medication alone during office visits was significantly higher in the last, relative to the first period (relative risk ratio = 2.42, 95% CI 1.24-4.72)., Conclusions: The proportion of outpatient visits that included a diagnosis of anxiety increased over time, accompanied by a decrease in the proportion of visits with therapy., (Copyright © 2023 by the American Academy of Pediatrics.)

BackgroundThe role of schools in SARS-CoV-2 transmission has been a debated topic since the beginning of the COVID-19 pandemic.AimTo examine SARS-CoV-2 transmission in all schools in Ireland during the 2020-21 school year.MethodsIn a national descriptive cross-sectional study, we investigated PCR-confirmed cases of COVID-19 among students (aged < 20 years) and staff (aged ≥ 20 years) who attended school during their infectious period to identify school close contacts. SARS-CoV-2 PCR test results of all school close contacts were pooled to obtain an overall positivity rate and to stratify positivity rate by school setting and role (i.e. student or staff).ResultsIn total, 100,474 individuals were tested as close contacts in 1,771 schools during the 2020-21 school year. An overall close contact positivity rate of 2.4% was observed across all schools (n = 2,373 secondary cases). The highest positivity rate was seen in special schools (3.4%), followed by primary (2.5%) and post-primary schools (1.8%) (p < 0.001). Of the close contacts identified, 90.5% (n = 90,953) were students and 9.5% (n = 9,521) were staff. Overall, students had a significantly higher positivity rate than staff (2.4% vs 1.8%, p < 0.001).ConclusionThis study demonstrated that a low level of SARS-CoV-2 transmission occurred in Irish schools during the 2020-21 academic year. In the event of future pandemics, and as the COVID-19 pandemic continues, there is a need to carefully weigh up the harms and benefits associated with disrupted education to mitigate infectious disease transmission before reflexively closing classes or schools.

Aims: Homeless mothers with young children in their care contend with high rates of substance use and low self-efficacy. However, a limited number of studies have examined these outcomes associated with housing and supportive services., Design: Participants were randomly assigned to: (1) housing + support services (n = 80), (2) housing-only (n = 80), or (3) services as usual (SAU) (n = 80) and were re-assessed at 3-, 6-, 9- and 12-months postbaseline., Settings: The study recruited a community-based sample from homeless service agencies and advertisements in a large Midwestern city., Participants: The study recruited two hundred forty (N = 240) women between the ages of 18 to 24 years, experiencing homelessness and with a substance use disorder (SUD) who also had a biological child under the age of 6 years in their care., Measurements: We measured frequency of alcohol and drug use using the Form 90 semi-structured interview, and self-efficacy using Pearlin and Schooler's (1978) 7-item Mastery Scale., Findings: Overall, mothers showed significant improvement in substance use and self-efficacy over time in each condition. However, as expected, patterns of change differentiated intervention groups with more mothers showing better substance use and self-efficacy outcomes in housing + supportive services than in SAU. Unexpectedly, more mothers in SAU showed better outcomes than those in housing-only., Conclusions: Substance use decreased and self-efficacy increased over time, but patterns of change characterized the intervention groups. In particular, findings suggest that when providing housing to this population, supportive services should also be offered., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Nearly 1 in every 14 youth have had a parent incarcerated at some point. In any given year, over 9 million adults from jail and 700,000 adults from prison return to their families and communities. However, few studies have explored the family experiences during re-entry or have provided suggestions on how to best support children during this time. The goal of this qualitative study was to describe family experiences and provide their considerations on how to better support children during the period of parent's re-entry. Qualitative data was gathered from 26 participants using semi-structured, in-depth phone interviews from March to August 2020. The sample included 10 youth (12-18 years) who have had a parent incarcerated, 10 custodial caregivers of youth who have had incarcerated parents, and 6 parents released from incarceration. Qualitative content analysis and open-coding procedures were used to determine themes across raters. Experiences centred on the challenges of assimilating to new family roles upon the parent returning home and to the community. Families also shared the difficulty in navigating parole restrictions and managing fears surrounding the recidivism of the parent. Three primary themes were deduced as relationship-building obstacles, unaligned family expectations and parole-related family burdens. Results from this study revealed suggestions that may address youth, caregiver and returning parent's needs during the re-entry phase. Family counselling and peer support groups may improve the process of mending or forming relationships. Access to re-entry programs, mental health services, and parental education may better align family expectations. Transparent wrap-around social services and decreasing legal challenges may reduce the parole-related burdens on the family., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Purpose: We sought to compare outcomes between neoadjuvant therapy with a novel hormonal agent (NHA) prior to radical prostatectomy (neo-RP) and up-front radical prostatectomy (RP) in patients with high-risk prostate cancer (HRPC)., Materials and Methods: HRPC patients treated on 3 trials of neoadjuvant NHA followed by RP formed the neo-RP cohort (112). The RP group (259) comprised an observational cohort of HRPC patients undergoing RP without neoadjuvant therapy between 2010-2016 at our institution who met key eligibility criteria for the neoadjuvant trials (ie ≥3 positive biopsy cores and Gleason ≥4+3=7). Inverse probability of treatment weighting (IPTW) was used to minimize potential confounding factors when estimating treatment effects. The primary outcomes were time to biochemical recurrence (BCR) and metastasis-free survival (MFS)., Results: Before IPTW, the neo-RP cohort had higher rates of Gleason 9-10 cancer (46% vs 24%), cT3 disease (22% vs 5%), and PSA ≥20 ng/ml (14% vs 7%); after IPTW, the 2 cohorts were balanced. Overall, after IPTW, time to BCR (HR=0.25 [95% CI 0.18-0.37]) and MFS (HR=0.26 [0.15-0.46]) were significantly longer in the neo-RP compared to the RP cohort. Rates of adjuvant (7% vs 24%) and salvage therapy (34% vs 46%) were lower in the neo-RP cohort., Conclusions: Neoadjuvant therapy with an NHA prior to RP was associated with longer time to BCR and superior MFS compared to up-front RP in men with HRPC. These findings are hypothesis-generating but suggest benefit with neoadjuvant therapy with an NHA in HRPC, an approach which is currently being studied in the phase 3 PROTEUS trial (NCT03767244).

Extra domain B splice variant of fibronectin (EDB+FN) is an extracellular matrix protein (ECM) deposited by tumor-associated fibroblasts, and is associated with tumor growth, angiogenesis, and invasion. We hypothesized that EDB+FN is a safe and abundant target for therapeutic intervention with an antibody-drug conjugate (ADC). We describe the generation, pharmacology, mechanism of action, and safety profile of an ADC specific for EDB+FN (EDB-ADC). EDB+FN is broadly expressed in the stroma of pancreatic, non-small cell lung (NSCLC), breast, ovarian, head and neck cancers, whereas restricted in normal tissues. In patient-derived xenograft (PDX), cell-line xenograft (CLX), and mouse syngeneic tumor models, EDB-ADC, conjugated to auristatin Aur0101 through site-specific technology, demonstrated potent antitumor growth inhibition. Increased phospho-histone H3, a pharmacodynamic biomarker of response, was observed in tumor cells distal to the target site of tumor ECM after EDB-ADC treatment. EDB-ADC potentiated infiltration of immune cells, including CD3+ T lymphocytes into the tumor, providing rationale for the combination of EDB-ADC with immune checkpoint therapy. EDB-ADC and anti-PD-L1 combination in a syngeneic breast tumor model led to enhanced antitumor activity with sustained tumor regressions. In nonclinical safety studies in nonhuman primates, EDB-ADC had a well-tolerated safety profile without signs of either on-target toxicity or the off-target effects typically observed with ADCs that are conjugated through conventional conjugation methods. These data highlight the potential for EDB-ADC to specifically target the tumor microenvironment, provide robust therapeutic benefits against multiple tumor types, and enhance activity antitumor in combination with checkpoint blockade., (©2022 The Authors; Published by the American Association for Cancer Research.)

A prototype tool has been developed for deriving sediment distribution coefficients, K d , in the marine environment by harvesting simultaneous measurements of activity concentrations of radionuclides in seawater and sediments based on the International Atomic Energy Agency's Marine Radioactivity Information System (MARIS). As a case study, the K d variability in the Baltic Sea was investigated as this region has been extensively monitored by HELCOM since 1984 resulting in a comprehensive dataset with good spatial and temporal coverage and required ancillary parameters. The prototype tool was used to derive a dataset of in-situ apparent K d(a) values derived from measurements of seawater and sediment in quasi-equilibrium conditions from the Baltic Sea over a period of approximately 35 years. For Cs, a comprehensive analysis of the Baltic Sea K d(a) dataset was undertaken, focusing on the temporal trend of K d(a) and comparing the results to K d values derived elsewhere. For Sr and Pu, for which there were fewer data records available a more rudimentary analysis was carried out. The Cs K d(a) median values derived from 137 Cs data in this study were estimated to be 2154 l kg -1 for seabed sediment and 10 000 l kg -1 for suspended sediment. The value derived for seabed sediment is in good agreement with the previously recommended ocean margin Cs K d value of 4000 l kg -1 . The analysis demonstrated the important distinction in the Baltic Sea between K d values for seabed sediment and suspended sediments, which differed by an order of magnitude. The analysis also highlighted the dependence of K d values on the variation in both the salinity of seawater and the type of seabed sediment. Such variability can significantly influence outcomes when modelling the behaviour of radionuclides in marine dispersion modelling., (© 2022 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Background: Implementation facilitation is an effective strategy to support the implementation of evidence-based practices (EBPs), but our understanding of multilevel strategies and the mechanisms of change within the "black box" of implementation facilitation is limited. This implementation trial seeks to disentangle and evaluate the effects of facilitation strategies that separately target the care team and leadership levels on implementation of a collaborative care model in pediatric primary care. Strategies targeting the provider care team (TEAM) should engage team-level mechanisms, and strategies targeting leaders (LEAD) should engage organizational mechanisms., Methods: We will conduct a hybrid type 3 effectiveness-implementation trial in a 2 × 2 factorial design to evaluate the main and interactive effects of TEAM and LEAD and test for mediation and moderation of effects. Twenty-four pediatric primary care practices will receive standard REP training to implement Doctor-Office Collaborative Care (DOCC) and then be randomized to (1) Standard REP only, (2) TEAM, (3) LEAD, or (4) TEAM + LEAD. Implementation outcomes are DOCC service delivery and change in practice-level care management competencies. Clinical outcomes are child symptom severity and quality of life., Discussion: This statewide trial is one of the first to test the unique and synergistic effects of implementation strategies targeting care teams and practice leadership. It will advance our knowledge of effective care team and practice-level implementation strategies and mechanisms of change. Findings will support efforts to improve common child behavioral health conditions by optimizing scale-up and sustainment of CCMs in a pediatric patient-centered medical home., Trial Registration: ClinicalTrials.gov, NCT04946253 . Registered June 30, 2021., (© 2022. The Author(s).)

222 Rn and 226 Ra concentrations of less than a few to several thousands of Bq L - 1 have been observed in several underground bodies of water around the world. Although regulations for these concentrations in water have been implemented internationally, there are currently no regulations in place in Japan. However, concentrations that exceed these internationally recognized regulatory values have also been observed in Japan. In this study, concentrations in spring water in the northern part of Japan were measured and the effective dose from intake of the water was evaluated. 222 Rn concentrations were measured using a liquid scintillation counter, and 226 Ra concentrations were measured using a high purity germanium detector after chemical preparation. The measured 222 Rn concentrations (=12.7 ± 6.1 Bq L -1 ) and 226 Ra concentrations (<0.019-0.022 Bq L -1 ) did not exceed the reference values set by international and European/American organizations. A conservative estimate of the annual effective ingestion dose of 8 μSv for 222 Rn and 226 Ra obtained in this study is much smaller than the estimated overall annual effective dose of 2.2 mSv from natural radiation to the Japanese population. However, this dosage accounts for 8% of the WHO individual dosing criteria of 0.1 mSv/year for drinking water.

Introduction: The effects of homelessness on pregnant women are substantial. We aim to identify key characteristics of a group of women identified as homeless and pregnant in order to understand their history of housing, family composition, health, and demographics as a first step for future intervention., Methods: We present cross-sectional survey data on a sample of 100 women reporting homelessness and pregnancy in the prior year in Columbus, Ohio, identified through social service and housing not for profit agencies. Our analysis uses data collected from a survey of health behaviors, housing, employment status, and demographics. Continuous measures are described with means and standard deviations, and categorical variables are described with percentages., Results: The majority (81%) of the women identified as African American. Over 95% of the women were single, and 74 women reported a prior pregnancy. Almost half of the women reported being behind on rent at least one time in the last 6 months, and 43% indicated that they had lived in more than three places in the last year. Approximately 34% of the sample reported cigarette use during pregnancy, while 12% and 30% reported alcohol and illicit drug use, respectively., Discussion: Women who were pregnant and experiencing homelessness in our study reported a multitude of complex and severe problems ranging from high rates of substance use, longstanding housing insecurity and financial stress. Programs hoping to successfully support women will need to address a variety of service needs while recognizing the resilience of many women., (© 2021. The Author(s).)

Low-resource individuals are at increased risk of obesity and cardiovascular disease (CVD), partially attributable to poor dietary patterns and dysfunctional microbiota. Dietary patterns in childhood play critical roles in physiological development and are shaped by caregivers, making caregiver-child dyads attractive targets for dietary interventions to reduce metabolic disease risk. Herein, we targeted low-resource caregiver-child dyads for a 10-week, randomized, controlled, multifaceted lifestyle intervention including: nutrition and physical activity education, produce harvesting, cooking demonstrations, nutrition counseling, and kinetic activites; to evaluate its effects on dietary patterns, CVD risk factors, and microbiome composition. Subjects in the lifestyle intervention group improved total diet quality, increased whole grain intake, decreased energy intake, and enhanced fecal elimination of the microbe-derived metabolite lithocholic acid (LCA) in contrast to control subjects. Microbiomes were highly personalized, similar within dyads, and altered by lifestyle intervention. Differential modeling of microbiome composition identified taxa associated with total diet quality, whole grain intake, and LCA elimination including recognized fiber-degrading bacteria such as Subdoligranulum , and bile acid metabolizing organisms like Bifidobacterium . Inclusion of taxa identified in diet and metabolite modeling within blood pressure models improved prediction accuracy of microbiome-blood pressure associations. Importantly, microbiota-blood pressure relationships were shared between dyads, implying shared host-microbiota responses to lifestyle intervention. Overall, these outcomes provide insight into mechanisms by which dietary interventions impact the gut-cardiovascular axis to reduce future CVD risk. Registered at clinicaltrials.gov: NCT05367674.

Homeless youth experience high rates of suicidal ideation and attempts, yet limited research has examined predictors of treatment engagement among this population. Suicidal homeless youth (N = 150) between the ages of 18 and 24 years were recruited from a drop-in center in Columbus, Ohio. Participants were randomly assigned to Cognitive Therapy for Suicide Prevention + treatment as usual through a local drop-in center (CTSP + TAU) (N = 75) or TAU alone (N = 75), and treatment attendance among those assigned to CTSP + TAU was examined in this study. As expected, among youth engaged in CTSP + TAU, those with a history of intimate partner violence (IPV) showed decreased odds of treatment attendance. Additionally, youth randomized into CTSP + TAU with higher acquired capability for suicide (ACS) scores and those identifying as Black were more likely to attend treatment sessions. Findings suggest that effective treatment implementation must consider youth's trauma history, demographics and severity of suicidal ideation and behaviors., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Youths with special healthcare needs face challenges transitioning from pediatric to adult health care. Understanding possible mechanisms contributing to poor healthcare transition could improve care. This study explores associations between health literacy (HL), transition readiness, and healthcare utilization., Methods: Youths with special healthcare needs aged 12-18 years were recruited from a Medicaid accountable care organization (2012-2017). Outcome measures included transition readiness (Transition Readiness Assessment Questionnaire), and healthcare utilization (any well-check, hospitalization, emergency department [ED] visit, or ambulatory sensitive condition ED visit). Multivariate regression analyses examined whether HL (adequate vs. inadequate) predicted outcomes, after adjusting for covariates. Models were then created to examine whether the effect of HL on healthcare utilization was mediated by transition readiness., Results: Among 417 youths with special healthcare needs, 67.1% reported adequate HL. Relative to inadequate HL, teens with adequate HL had significantly higher average Transition Readiness Assessment Questionnaire-20 scores (β = .34, p < .001). Controlling for covariates, HL was a significant predictor of having an ambulatory sensitive condition ED visit and having any ED visits neared significance. There was a positive transition readiness mediation effect on having an ED visit, with higher transition readiness being associated with higher odds of having any ED visit in the mediation analysis., Conclusions: HL is independently associated with higher transition readiness and lower ambulatory sensitive condition ED use, but pathways of action require further study., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Mass incarceration has had an undeniable toll on childhood poverty and inequality, however, little is known about the consequences on pediatric health. The purpose of this study was to identify and describe the health of pediatric patients with probable personal or family history involvement with the correctional system., Methods: A descriptive study was conducted using electronic health record data of 2.3 million youth (ages 0-21 years) who received care in a large Midwestern hospital-based institution from February 2006-2020. We employed a correctional-related keyword search (e.g. jail, prison, probation, parole) to locate youth with probable personal or family history involvement. Health characteristics were measured as clinician diagnostic codes., Results: Two percent of the total pediatric population had a correctional keyword in the medical chart (N = 51,855). This 2% made up 66% of all patients with cannabis-related diagnoses, 52% of all patients with trauma-related diagnoses, 48% of all stress-related diagnoses, 38% of all patients with psychotic disorder diagnoses, and 33% of all suicidal-related disorders within this institution's electronic health record database - among other highly concerning findings., Conclusions: We captured an alarming health profile that warrants further investigation and validation methods to better address the gaps in our clinical understanding of youth with personal or family history involvement with the correctional system. We can do better in identifying, and supporting families affected by the correctional system., (© 2021. The Author(s).)

Background: Youth experiencing homelessness are at high risk for suicide, yet few studies have evaluated risk reduction interventions targeting suicidal ideation in this vulnerable population. A comprehensive approach to risk-reduction is needed that addresses basic needs and provides targeted interventions for those at highest risk. The protocol described builds on the design of the first randomized trial of Housing First (HF) for homeless youth. The primary objective is to determine whether housing combined with supportive services that include suicide screening and targeted psychotherapy (Cognitive Therapy for Suicide Prevention) is effective for reducing suicidal ideation and other secondary outcomes (depression and suicide attempts). Additionally, we will explore mediators of the treatment effect (housing stability and substance use) and determinants of implementation., Methods: Youth recruited to the HF trial will be randomized to HF + supportive services (n = 120), or supportive services alone (n = 120). The "Suicide Treatment Education and Prevention" (STEP) protocol will additionally screen youth in both arms at baseline and 3 months for suicidal ideation (SSI-W). Those who screen as moderate risk for suicide (SSI-W ≥ 10) will be offered CTSP, which includes up to 9 sessions over the first 6 months following enrollment. CTSP will be delivered in one-on-one sessions by a trained advocate. Research assessments will be collected to assess outcomes (including suicidal ideation) at baseline, 3, 6, 9 and 12 months. Qualitative interviews with subjects receiving CTSP and other stakeholders will explore implementation determinants., Discussion: The study will fill an important gap in the literature about the added benefit of HF combined with supportive services including suicide screening and treatment for reducing suicidal ideation in homeless youth. With the urgent need to address both homelessness and suicide risk, evidence is needed about services that can be integrated into delivery settings for youth experiencing homelessness., Trial Registration: NCT04135703 . Date of registration: October 23, 2019.

Short chain fatty acids (SCFAs), generated from microbial fermentation of dietary fibers, can regulate weight, appetite and energy homeostasis. Therefore, measuring SCFAs in fecal samples is important to understand the relationship between dietary patterns, gut microbial metabolism, and their impact on host metabolism homeostasis. However, due to the chemical complexity of fecal samples and the volatility of these SCFAs, the quantitative measurements of SCFAs remain challenging. In this study, we developed an absolute quantitation method for accurate and reliable analysis of SCFAs using an UPLC-Q Exactive HRMS system. Nine C2-C6 SCFAs were first derivatized and then separated on a reversed-phase CSH C18 column, and quantitated by UPLC-HRMS with targeted-selected ion monitoring (t-SIM) mode. Our calibration plots showed high linearity (R 2 >0.99) with high quantitation accuracy (from 91.24%-118.42%); additional analyses showed excellent precisions ranging from 1.12 % to 6.13 %, and accurate recoveries between 92.38 % and 109.65 % with relative standard deviations of 0.31 %-6.44 %. Meanwhile, the short-term stability, freeze and thaw stability, and 168 h storage stability were tested and reported from 85.07%-106.44% with RSDs 0.44%-20.00%, 98.99%-128.84% with RSDs 0.77%-19.79%, and 77.53%-104.42% with RSDs 0.92%-18.65%, respectively. Lastly, this quantitative method was applied to determine the SCFA concentrations and compositions in forty fecal samples from a group of study subjects participating in an obesity prevention trial, and a broad range of concentrations was noted for the detected SCFAs., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Growth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, and higher circulating levels are associated with cachexia and reduced survival in cancer and other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated and highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, weight loss, and mortality in rodents. LPS injection transiently increased circulating GDF15 in wild-type mice, decreased food intake and body weight, and increased illness behavior and mortality at a high dose. GDF15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. Similarly, in GDF15 knockout mice, the LPS effect on appetite and survival was comparable with that observed in wild-type controls. Therefore, effective inhibition of circulating active GDF15 via an antibody or via gene knockout demonstrated that survival in the LPS acute inflammation model was independent of GDF15., Competing Interests: R.J.S. is a member of the advisory boards of Novo Nordisk, Scohia, Kintai Therapeutics, and Ionis. D.M.B., S.J., C.Z., S.J., X.L., L.K., J.P., K.H., E.Z.Q., D.B., M.L., K.K., Z.W., B.B.Z., and L.L. are employees and shareholders of Pfizer. N.B.V., T.H., and O.B. were employees of Pfizer during the conduct of the study and are current employees of Dicerna Pharmaceuticals, Inc., JOINN Biologics, and Cellarity, respectively. A.P. declares no conflict of interest., (© 2021 Elsevier Inc.)

Background: Homeless youth experience high rates of substance use disorders, exposures to violence, mental and physical health conditions, and mortality. They have been particularly affected by the opioid crisis. However, no study to date has used a randomized controlled design to test preventive interventions of opioid and other drug use among this vulnerable population. Resolution of youth homelessness through housing and supportive services including prevention services, often referred to as "Housing First," has great potential to reduce the likelihood for the development of an opioid use disorder as well as other problem behaviors associated with living on the streets. Housing First has been tested through randomized trials among homeless adults with mental health and substance use disorders, but has not been empirically tested for opioid prevention among homeless youth., Methods: Homeless youth will be recruited from a drop-in shelter site frequented by disconnected youth; they will be screened for eligibility, including current homelessness, age 18-24 years, and not currently meeting criteria for opioid use disorder (OUD). In a controlled trial, 240 youth will then be randomized to one of two conditions, (1) housing + opioid and related risk prevention services, or (2) opioid and related risk prevention services alone. This project utilizes existing efficacious models of prevention to address opioid-related risks, including motivational interviewing, strengths-based outreach and advocacy, and an HIV risk preventive intervention. Follow-up will be conducted at 3, 6, 9 and 12-months post-baseline. The economic cost of each intervention will be determined to support implementation decisions with other providers and their funders., Discussion: This study will provide essential information for researchers and providers on the efficacy of housing + opioid and related risk prevention services in an RCT for effects on opioid use and mechanisms underlying change. Because youth experiencing homelessness are at increased risk for a variety of adverse outcomes, the proposed intervention may produce substantial health care benefits to the youths and society at large. Trial registration ClinicalTrials.gov, NCT04135703, Registered October 13, 2019, https://clinicaltrials.gov/ct2/show/NCT04135703?term=NCT04135703&draw=2&rank=1#contacts.

GDF15 is a distant TGF-β family member that induces anorexia and weight loss. Due to its function, GDF15 has attracted attention as a potential therapeutic for the treatment of obesity and its associated metabolic diseases. However, the pharmacokinetic and physicochemical properties of GDF15 present several challenges for its development as a therapeutic, including a short half-life, high aggregation propensity, and protease susceptibility in serum. Here, we report the design, characterization and optimization of GDF15 in an Fc-fusion protein format with improved therapeutic properties. Using a structure-based engineering approach, we combined knob-into-hole Fc technology and N-linked glycosylation site mutagenesis for half-life extension, improved solubility and protease resistance. In addition, we identified a set of mutations at the receptor binding site of GDF15 that show increased GFRAL binding affinity and led to significant half-life extension. We also identified a single point mutation that increases p-ERK signaling activity and results in improved weight loss efficacy in vivo. Taken together, our findings allowed us to develop GDF15 in a new therapeutic format that demonstrates better efficacy and potential for improved manufacturability.

Early neural development and maternal health have critical long-term effects on children's mental health and outcomes later in life. As child mental disorders continue to rise nationwide, a number of states are considering new ways of investing in the critical early childhood period to prevent later poor outcomes and reduce the burden on the mental health system. Because most state mental health authorities (SMHAs) have no dedicated mental health dollars to devote to this early, crucial period of child development, building coalitions is key to implementing prevention and promotion programming. The authors describe two issues-coalition building and contractual considerations-that should be considered as SMHAs develop these types of policies or plan new prevention and promotion initiatives. Coalition building includes establishing the structural conditions for implementing a prevention or promotion initiative, resolving workforce issues (i.e., who will carry the program out), and engaging communities and families in the effort. Contractual considerations include establishing agreed-upon measures and metrics to monitor outcomes, assigning accountability for those outcomes, and delineating realistic time frames for these investments before expecting improved outcomes. The promise of moving services upstream to support early childhood development, to prevent mental health issues from derailing children's development, and to promote children's well-being are goals that are within reach.

This article argues that value-based health systems may contract with school districts engaged in capitated special education to achieve better patient outcomes and lower costs for the pediatric population.

Objective: 1) Assess whether rural-urban disparities are present in pediatric preventive health care utilization; and 2) use regression decomposition to measure the contribution of social determinants of health (SDH) to those disparities., Methods: With an Ohio Medicaid population served by a pediatric Accountable Care Organization, Partners For Kids, between 2017 and 2019, we used regression decomposition (a nonlinear multivariate regression decomposition model) to analyze the contribution of patient, provider, and SDH factors to the rural-urban well-child visit gap among children in Ohio., Results: Among the 453,519 eligible Medicaid enrollees, 61.2% of urban children received a well-child visit. Well-child visit receipt among children from large rural cities/towns and small/isolated towns was 58.2% and 55.5%, respectively. Comparing large rural towns to urban centers, 55.8% of the 3.0 percentage-point difference was explained by patient, provider, and community-level SDH factors. In comparing small/isolated town to urban centers, 89.8% of the 5.7 percentage-point difference was explained by these characteristics. Of provider characteristics, pediatrician providers were associated with increased well visit receipt. Of the SDH factors, unemployment and education contributed the most to the explained difference in large rural towns while unemployment, education, and food deserts contributed significantly to the small/isolated town difference., Conclusions: The receipt of pediatric preventive care is slightly lower in rural communities. While modest, the largest part of the rural-urban preventive care gap can be explained by differences in provider type, poverty, unemployment, and education levels. More could be done to improve pediatric preventive care in all communities., (Copyright © 2020 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

The biological effects of low dose-rate radiation exposures on humans remains unknown. In fact, the Japanese nation still struggles with this issue after the Fukushima Dai-ichi Nuclear Power Plant accident. Recently, we have found a unique area in Indonesia where naturally high radiation levels are present, resulting in chronic low dose-rate radiation exposures. We aimed to estimate the comprehensive dose due to internal and external exposures at the particularly high natural radiation area, and to discuss the enhancement mechanism of radon. A car-borne survey was conducted to estimate the external doses from terrestrial radiation. Indoor radon measurements were made in 47 dwellings over three to five months, covering the two typical seasons, to estimate the internal doses. Atmospheric radon gases were simultaneously collected at several heights to evaluate the vertical distribution. The absorbed dose rates in air in the study area vary widely between 50 nGy h -1 and 1109 nGy h -1 . Indoor radon concentrations ranged from 124 Bq m -3 to 1015 Bq m -3 . That is, the indoor radon concentrations measured exceed the reference levels of 100 Bq m -3 recommended by the World Health Organization. Furthermore, the outdoor radon concentrations measured were comparable to the high indoor radon concentrations. The annual effective dose due to external and internal exposures in the study area was estimated to be 27 mSv using the median values. It was found that many residents are receiving radiation exposure from natural radionuclides over the dose limit for occupational exposure to radiation workers. This enhanced outdoor radon concentration might be as a result of the stable atmospheric conditions generated at an exceptionally low altitude. Our findings suggest that this area provides a unique opportunity to conduct an epidemiological study related to health effects due to chronic low dose-rate radiation exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We report here the discovery and optimization of a novel T cell retargeting anti-GUCY2C x anti-CD3ε bispecific antibody for the treatment of solid tumors. Using a combination of hybridoma, phage display and rational design protein engineering, we have developed a fully humanized and manufacturable CD3 bispecific antibody that demonstrates favorable pharmacokinetic properties and potent in vivo efficacy. Anti-GUCY2C and anti-CD3ε antibodies derived from mouse hybridomas were first humanized into well-behaved human variable region frameworks with full retention of binding and T-cell mediated cytotoxic activity. To address potential manufacturability concerns, multiple approaches were taken in parallel to optimize and de-risk the two antibody variable regions. These approaches included structure-guided rational mutagenesis and phage display-based optimization, focusing on improving stability, reducing polyreactivity and self-association potential, removing chemical liabilities and proteolytic cleavage sites, and de-risking immunogenicity. Employing rapid library construction methods as well as automated phage display and high-throughput protein production workflows enabled efficient generation of an optimized bispecific antibody with desirable manufacturability properties, high stability, and low nonspecific binding. Proteolytic cleavage and deamidation in complementarity-determining regions were also successfully addressed. Collectively, these improvements translated to a molecule with potent single-agent in vivo efficacy in a tumor cell line adoptive transfer model and a cynomolgus monkey pharmacokinetic profile (half-life>4.5 days) suitable for clinical development. Clinical evaluation of PF-07062119 is ongoing.

Four recent reports from the National Academies of Sciences, Engineering, and Medicine framed around the issues of poverty; mental, emotional, and behavioral health; adolescence; and young family health and education build on extensive recent evidence of what can be done to improve the health and well-being of children, youth, and families. We describe the process of generating the reports, briefly summarize each report's content, and identify crosscutting themes and recommendations. We also note how the coronavirus disease 2019 (COVID-19) pandemic highlights major disparities and systemic problems addressed in the reports and heightens the relevance of their policy recommendations. The reports issue a unified, urgent call for measures with the potential to change the trajectory and outcomes for children and youth. Among these are basic income supports, other family supports, universal health care structured to meet family needs, and a broad national policy that prioritizes children and youth.

Background: Homelessness among youth is devastating, with high rates of substance use disorders and mental health comorbidity. Mindfulness-based interventions that include meditation and mindfulness skills training reduce stress and symptoms of anxiety or depression. However, engaging high-risk youth in interventions is challenging. Virtual reality is a more flexible platform for delivering meditation and may be appealing to youth., Objective: The study objectives were to evaluate the feasibility of delivering virtual reality meditation and of collecting outcome measures, including anxiety and physiologic stress., Methods: A sample of 30 youth experiencing homelessness was enrolled in the study. Youth were randomized to receive 10 minutes of one of three interventions: (1) virtual reality meditation, (2) audio meditation (through a web-based platform), or (3) virtual reality imagery of historical pictures and text. Subjects who consented to the study attended two research visits. The first visit collected survey measures of demographics, mental health, and substance use, and oriented subjects to the intervention platforms. The second visit (1-3 days later) delivered the intervention and collected pre and post outcome measures of anxiety and physiologic stress (salivary cortisol). Changes in anxiety and cortisol at the second visit were compared across groups using a linear regression model in which the primary analysis compared virtual reality meditation to audio meditation and secondary analyses compared virtual reality meditation to virtual reality imagery., Results: Anxiety scores decreased in all groups, with a larger reduction among the virtual reality meditation group (difference=10.8) compared to the web-based meditation or virtual reality images groups (difference=5.8 and 5.0, respectively). After controlling for baseline values, there were no significant group differences in changes in anxiety scores or cortisol levels. In comparing virtual reality meditation and audio meditation, the effect size for anxiety was moderate (Cohen d=0.58) while the effect size for cortisol was small (Cohen d=0.08)., Conclusions: Preliminary results suggest that virtual reality meditation has a moderate benefit for anxiety but not physiologic stress. Future research is needed to confirm these results in a larger sample and to investigate whether the effects are sustained or increase with repeated use of virtual reality mediation. Virtual reality meditation appears feasible to deliver among homeless youth and merits further study., Trial Registration: ClinicalTrials.gov NCT04004520; https://clinicaltrials.gov/ct2/show/NCT04004520., (©Laura Johnson Chavez, Kelly Kelleher, Natasha Slesnick, Eugene Holowacz, Ellison Luthy, Laura Moore, Jodi Ford. Originally published in JMIR Mental Health (http://mental.jmir.org), 24.09.2020.)

Monoclonal antibodies (mAbs) can be engineered to have "extended half-life" and "catch and release" properties to improve target coverage. We have developed a mAb physiologically-based pharmacokinetic model that describes intracellular trafficking, neonatal Fc receptor (FcRn) recycling, and nonspecific clearance of mAbs. We extended this model to capture target binding as a function of target affinity, expression, and turnover. For mAbs engineered to have an extended half-life, the model was able to accurately predict the terminal half-life (82% within 2-fold error of the observed value) in the human FcRn transgenic (Tg32) homozygous mouse and human. The model also accurately captures the trend in pharmacokinetic and target coverage data for a set of mAbs with differing catch and release properties in the Tg32 mouse. The mechanistic nature of this model allows us to explore different engineering techniques early in drug discovery, potentially expanding the number of "druggable" targets., (© 2020 Pfizer. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Activity concentrations of 234 U, 235 U, 238 U, 226 Ra, 228 Ra, 222 Rn, 210 Po, 210 Pb, 40 K, 3 H, 14 C, 134 Cs and 137 Cs were determined in 20 different Japanese bottled drinking water commercially available in Japan. The origins of the mineral water samples were geographically distributed across different regions of Japan. Activity concentrations above detection limits were measured for the radionuclides 234 U, 235 U, 238 U, 226 Ra, 228 Ra and 210 Po. An average total annual effective dose due to ingestion was estimated for adults, based on the average annual volume of bottled water consumed in Japan in 2019, reported to be 31.7 L/y per capita. The estimated dose was found to be below the recommended World Health Organisation (WHO) guidance level of 0.1 mSv/y for drinking water quality. The most significant contributor to the estimated dose was 228 Ra.

Roughly 60 years after the first questions were raised about hospitalized patients, Kaslow and colleagues (see record 2020-40858-010) articulate the importance of patient- and family-centered care and outline recommendations for hospitalist care teams. They concisely point out the need for such practices, but more important, they provide many practical examples. Some of the main recommendations include (a) form partnerships, (b) prioritize communication, (c) discuss care goals, (d) share decision-making, (e) collaborate to implement the treatment plan, (f) negotiate differences, and (g) make special accommodations for discharge planning. Within each of these areas, the authors provide specific patient-centered and family-focused practices. At a global level, none of the recommendations provided are unique to hospitalists' practice. Almost all of them are similar to patient- and family-centered care recommendations from other settings. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

For an antibody to be a successful therapeutic many competing factors require optimization, including binding affinity, biophysical characteristics, and immunogenicity risk. Additional constraints may arise from the need to formulate antibodies at high concentrations (>150 mg/ml) to enable subcutaneous dosing with reasonable volume (ideally <1.0 mL). Unfortunately, antibodies at high concentrations may exhibit high viscosities that place impractical constraints (such as multiple injections or large needle diameters) on delivery and impede efficient manufacturing. Here we describe the optimization of an anti-PDGF-BB antibody to reduce viscosity, enabling an increase in the formulated concentration from 80 mg/ml to greater than 160 mg/ml, while maintaining the binding affinity. We performed two rounds of structure guided rational design to optimize the surface electrostatic properties. Analysis of this set demonstrated that a net-positive charge change, and disruption of negative charge patches were associated with decreased viscosity, but the effect was greatly dependent on the local surface environment. Our work here provides a comprehensive study exploring a wide sampling of charge-changes in the Fv and CDR regions along with targeting multiple negative charge patches. In total, we generated viscosity measurements for 40 unique antibody variants with full sequence information which provides a significantly larger and more complete dataset than has previously been reported., Competing Interests: Pfizer provided support for this research including salaries for authors JA, AT, RS, SM, AK, HY, KK, DM, AD, GY, XZ, LR, WM, DF, GC, EB and LL. However, Pfizer did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Pfizer’s support does not alter our adherence to PLOS ONE policies on sharing data and materials.