Adolescent Healthcare Access: A Qualitative Study of Provider Perspectives.

INTRODUCTION: Adolescent access to quality healthcare is key to prevention and early intervention for health risk behaviors. This paper provides a healthcare provider perspective on barriers and facilitators to youth accessing care. METHODS: Five focus groups were conducted from November to December 2020 with providers from a variety of healthcare settings. Participants were asked to describe their respective adolescent patient populations, adolescent-specific health concerns, and organizational accommodations specific for youth services. Transcripts were analyzed using Inductive Thematic Analysis and themes were grouped using a social-ecological framework. RESULTS: At an individual level, providers noted that an adolescent's knowledge and ability to navigate services varied greatly across settings. Providers identified provider trust and parent/guardian support as key interpersonal factors that support adolescents' access to services. Organizational factors included bureaucratic barriers and the clinic's reputation among youth. Community factors centered on mistrust within healthcare systems and stigmatization of seeking certain types of services. Participants also described how state-level policies influence parent/guardian consent requirements, which can limit adolescents' access to care. CONCLUSION: Adolescent access to and utilization of healthcare in the United States is a complex problem requiring systems-level change. Healthcare organizations and providers have the opportunity and capacity to positively influence adolescents' healthcare access and experiences, however a lack of standardized, clinic-level priorities and guidelines can limit adolescent-centered care.

Rational downstream development for adeno-associated virus full/empty capsid separation - A streamlined methodology based on high-throughput screening and mechanistic modeling.

Recombinant adeno-associated virus (AAV) has emerged as one of the most promising systems for therapeutic gene delivery and has demonstrated clinical success in a wide range of genetic disorders. However, manufacturing of high-quality AAV in large amounts still remains a challenge. A significant difficulty for downstream processing is the need to remove empty capsids that are generated in all currently utilized expression systems and that represent product-related impurities that adversely affect safety and efficacy of AAV vectors. Empty and full capsids exhibit only subtle differences in surface charge and size, making chromatography-based separations highly challenging. Here, we present a rapid methodology for the systematic process development of the crucial AAV full/empty capsid separation on ion-exchange media based on high-throughput screening and mechanistic modeling. Two of the most commonly employed serotypes, AAV8 and AAV9, are used as case studies. First, high-throughput studies in filter-plate format are performed that allow the rapid and comprehensive study of binding and elution behavior of AAV on different resins, using different buffer systems, pH, salt conditions, and solution additives. Small amounts of separated empty and full AAV capsids are generated by iodixanol gradient centrifugation that allow studying the binding and elution behavior of the two vector species separately in miniaturized format. Process conditions that result in maximum differences in elution behavior between empty and full capsids are then transferred to benchtop chromatography systems that are used to generate calibration data for the estimation of steric mass-action isotherm and mass transport parameters for process simulation. The resulting column models are employed for in-silico process development that serves to enhance understanding of separation constraints and to identify optimized conditions for the removal of empty particles. Finally, optimized separation conditions are verified experimentally. The methodology presented in this work provides a systematic framework that affords mechanistic understanding of the crucial empty/full capsid separation and accelerates the development of a scalable AAV downstream process.

Development of Youth-Centered Health Messaging Posters for High School-Based Health Clinics in Hawaii.

BACKGROUND: Youth may be reluctant to seek health care from school health providers due to feeling embarrassed or stigmatized in the health office environment or worried about their confidentiality. The purpose of this project was to create a set of youth-centered health posters that promote youth engagement with nursing staff and to standardize health messaging across high schools in Hawaii school-based clinics. METHODS: Two community advisory boards, 1 composed of 10 youth stakeholders (mean age 17 years) and the other of 7 adult stakeholders, informed poster development utilizing web-based discussion groups. The discussions were transcribed, and additional data was collected using field notes and anonymous digital messages. Adult advisory board members also provided feedback on suggested poster text through an online survey. RESULTS: Youth and adult advisory board participants identified 4 key health concerns facing youth: confidentiality, sexual health, relationships, and mental health. Based on input from the 2 advisory boards, 4 posters were developed, each centered on 1 key health issue. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: School-based posters can convey important messages to help youth understand their health care rights and responsibilities, as well as identify important issues open for discussion with nurses. CONCLUSION: Posters are an underutilized tool for school health providers to create welcoming, inclusive health care environments and facilitate health-related conversations with youth. This paper describes participant feedback about the characteristics of a memorable poster and briefly outlines current knowledge and recommendations for school health providers regarding each of the 4 health issues.

Structural Disorder at the Edges of Rubrene Crystals Enhances Singlet Fission.

Materials that undergo singlet fission are of interest for their use in light-harvesting, photocatalysis, and quantum information science, but their ability to undergo fission can be sensitive to local variations in molecular packing. Herein we employ transient absorption microscopy, molecular dynamics simulations, and electronic structure calculations to interrogate how structures found at the edges of orthorhombic rubrene crystals impact singlet fission. Within a micrometer-scale spatial region at the edges of rubrene crystals, we find that the rate of singlet fission increases nearly 4-fold. This observation is consistent with formation of a region at crystal edges with reduced order that accelerates singlet fission by disrupting the symmetry found in rubrene's orthorhombic crystal structure. Our work demonstrates that structural distortions of singlet fission materials can be used to control fission in time and in space, potentially offering a means of controlling this process in light harvesting and quantum information applications.

The Development of a Systems-Level Approach to Address Adolescent Access to Health Care: A Novel Confidentiality Policy Intervention.

Most evidence-based interventions in adolescent sexual and reproductive health and mental health remain largely aimed at individual-level outcomes and do not conceptualize adolescent health within a social-ecological model. Interventions to affect policy, systems, and environmental change offer potential for sustained population impact. The current initiative used an innovation framework to develop a novel systems-level approach to address adolescent access to health care. The Framework for Public Health Innovation provided an approach to develop a novel intervention. Confident Teen is a systems-level intervention that creates the opportunity, through organizational policy change, to increase adolescents' access to confidential sexual and reproductive health services through organizational policies. Gaps in adolescents' access to health care services allowed for a systems-level approach to be designed through an adolescent pregnancy prevention innovation initiative. Confidentiality is a right and critical component to their health care; therefore, a policy and conversation between provider and patient is a prioritized component of the novel intervention.

Progress and Prospects in Optical Ultrafast Microscopy in the Visible Spectral Region: Transient Absorption and Two-Dimensional Microscopy.

Ultrafast optical microscopy, generally employed by incorporating ultrafast laser pulses into microscopes, can provide spatially resolved mechanistic insight into scientific problems ranging from hot carrier dynamics to biological imaging. This Review discusses the progress in different ultrafast microscopy techniques, with a focus on transient absorption and two-dimensional microscopy. We review the underlying principles of these techniques and discuss their respective advantages and applicability to different scientific questions. We also examine in detail how instrument parameters such as sensitivity, laser power, and temporal and spatial resolution must be addressed. Finally, we comment on future developments and emerging opportunities in the field of ultrafast microscopy.

Addressing Evaluation Barriers with Early Innovation Development for Adolescent-Focused Sexual and Reproductive Health Interventions.

Most evidence-based teen pregnancy prevention programs focus on individual-level sexual health outcomes (e.g., STIs, pregnancy, teen births). To expand program and intervention approaches within teen pregnancy prevention (TPP), the Department of Health and Human Services funded two grantees, Innovative Teen Pregnancy Prevention Programs (iTP3) and Innovation Next (IN) to support and enable early innovation to advance adolescent health and prevent teen pregnancy. The pipeline to support and enable innovation in adolescent health is complex, resulting in barriers and challenges to research and evaluation of novel programs. This paper presents some of the barriers encountered by the grantees. Data for this paper was collected from key personnel and secondary data sources. Focus group participants included seven representatives (n = 7) across the two organizations. Focus group questions assessed barriers related to innovative intervention development and evaluation. Key findings include four barriers to evaluation when fostering innovative adolescent-focused pregnancy prevention interventions. These included (a) funding constraints on evaluation activities, (b) innovation readiness for rigorous testing, (c) evaluation knowledge and expertise on innovation-development teams, and (d) challenges with evaluation requirements. Novel and promising system- and technology-focused interventions with the potential to impact TPP require alternative tools and approaches for evaluation. This would allow research to focus on how systems-level change mechanisms (i.e., policy, access to care) impact sexual risk behaviors and better understand ecological and social determinants of health for the priority population. The advancement of approaches to impact adolescent health identifies the need to expand the focus of evidence-based interventions beyond the adolescent themselves and understand approaches that impact external contexts and environments related to reducing sexual and reproductive health (SRH) risk-taking.

Continuity of maternal and infant care through integrated health service delivery networks in Latin America: a scoping review.

Latin America has experienced substantial development over the last three decades; however, development has been uneven with persistent inequalities, especially in the areas of maternal and child health. Since the early 1990s, most Latin American health-care systems have undergone a series of reforms to improve access to services, with the most recent being the implementation of integrated health service delivery networks (IHSDNs). This model posits that patients will receive better continuity of care and higher-quality health services and avoid duplicated efforts. While decreased maternal and infant mortality rates have been observed in the region since IHSDN implementation, there is limited evidence on this model's implications for maternal and infant care. The purpose of this study is to explore how IHSDNs affect access to and continuity of maternal and infant care in Latin America, according to the peer-reviewed literature. A scoping review was conducted systematically to identify peer-reviewed articles published since 2007 on studies that took place in Latin America, include IHSDNs, focus on the antenatal and/or postnatal period, include women and/or infants under 2 years of age and are written in English, Spanish or Portuguese. Seven studies (n = 7) met the inclusion criteria for this review. Barriers identified were related to person-centred care (n = 5) and logistical challenges (n = 5). The most cited facilitator encompassed social support for women when accessing care (n = 3). Potential solutions to improve care access included an improvement in the network structure and a greater focus on care provision, rather than regulations and compliance. Findings from this study suggest that the IHSDN model has the potential to improve care for women during pregnancy and post-birth if the model is implemented to its full extent. However, implementation of the model in Latin America is still weak, creating barriers for women when seeking care, particularly for disparate populations and those residing in rural areas.

HIV Nef Expression Down-modulated GFAP Expression and Altered Glutamate Uptake and Release and Proliferation in Astrocytes.

HIV infection of astrocytes leads to restricted gene expression and replication but abundant expression of HIV early genes Tat, Nef and Rev. A great deal of neuroHIV research has so far been focused on Tat protein, its effects on astrocytes, and its roles in neuroHIV. In the current study, we aimed to determine effects of Nef expression on astrocytes and their function. Using transfection or infection of VSVG-pseudotyped HIV viruses, we showed that Nef expression down-modulated glial fibrillary acidic protein (GFAP) expression. We then showed that Nef expression also led to decreased GFAP mRNA expression. The transcriptional regulation was further confirmed using a GFAP promoter-driven reporter gene assay. We performed transcription factor profiling array to compare the expression of transcription factors between Nef-intact and Nef-deficient HIV-infected cells and identified eight transcription factors with expression changes of 1.5-fold or higher: three up-regulated by Nef (Stat1, Stat5, and TFIID), and five down-regulated by Nef (AR, GAS/ISRE, HIF, Sp1, and p53). We then demonstrated that removal of the Sp1 binding sites from the GFAP promoter resulted in a much lower level of the promoter activity and reversal of Nef effects on the GFAP promoter, confirming important roles of Sp1 in the GFAP promoter activity and for Nef-induced GFAP expression. Lastly, we showed that Nef expression led to increased glutamate uptake and decreased glutamate release by astrocytes and increased astrocyte proliferation. Taken together, these results indicate that Nef leads to down-modulation of GFAP expression and alteration of glutamate metabolism in astrocytes, and astrocyte proliferation and could be an important contributor to neuroHIV.

Supporting and Enabling the Process of Innovation in Public Health: The Framework for Public Health Innovation.

This manuscript introduces a new framework for creating innovations in public health-the Framework for Public Health Innovation. The framework was developed through a longitudinal qualitative research study that investigated the process of creating innovative adolescent health programs. Interviews were conducted with a national sample of 26 organizations over two time points. Data collection focused on the process of innovative program development; organizational capacity; training; and technical assistance needs, successes, and barriers. The framework was developed and modified based on interview findings and expert advice; then, the final framework was validated with content experts. The framework illustrates a dynamic process of innovation that begins with dissatisfaction with the status quo, and then, illustrates three necessary components for innovation-space, process, and partnerships. Four categories of innovation, which range in complexity, are proposed: (1) creating a new component to an existing program, (2) adapting an existing program to meet new needs, (3) taking an alternative approach to addressing an existing program, and (4) reframing a health problem from a new perspective. As illustrated by a feedback loop, the resulting innovations disrupt the status quo. This model can be applied to any content area in public health and is useful for both research and practitioners.

Modeling the impact of a health coaching intervention to prevent teen pregnancy.

Teenage pregnancy is an important public health issue in the United States, presenting significant health and economic risks to adolescents and the society. Health coaching is a potentially effective intervention in preventing teen pregnancy. In 2017, the Children's Hospital of Philadelphia implemented a health coaching program among sexually active teenage girls, which improved their contraceptive continuation rates. However, the cost-effectiveness of the health coaching program is not clear. We developed a microsimulation model of teen pregnancy that can predict the number of teen pregnancies and related birth outcomes. Model parameters were estimated from the literature and the health coaching program. The teen pregnancy model was used to assess how the program could influence direct health care costs and pregnancy outcomes. Our model projected that the health coaching program could prevent 15 teen pregnancies per 1000 adolescents compared to no intervention. The incremental cost-effectiveness ratio (ICER) for the intervention was $309 per pregnancy prevented, which was less than the willingness-to-pay threshold of $4,206 per pregnancy. Thus, the health coaching intervention was cost-effective. Our study provides promising data on the effectiveness and cost-effectiveness of a health coaching intervention to reduce the burden of teen pregnancies. Health practitioners should consider implementing the program for a longer term and at a larger scale.

Implementation evaluation of a collective impact initiative to promote adolescent health in Oklahoma County, USA.

BACKGROUND: The teenage birth rate in the USA has considerably decreased in recent decades; however, more innovative, collaborative approaches are needed to promote adolescent health and prevent teenage pregnancy at the community level. Despite literature on the promising results of the collective impact (CI) model for health promotion, there is limited literature on the model's ability to reduce teenage pregnancies in a community. The Central Oklahoma Teen Pregnancy Prevention Collaboration is applying the CI model to foster collaboration among multiple stakeholders with the goal of increasing community and organizational capacity to improve adolescent health outcomes. This paper reports the findings from the initiative's implementation evaluation, which sought to understand whether the CI model improved collaboration among organizations and understand barriers and facilitators that affected program delivery. METHODS: Program implementers and evaluators jointly developed research questions to guide the intervention and evaluation design. The Consolidated Framework for Implementation Research (CFIR) was used to assess program components including the intervention characteristics, organization setting, community setting, facilitator characteristics, and the process of implementation. Primary sources of data included performance measures, meeting observations (n = 11), and semi-structured interviews (n = 10). The data was thematically analyzed using CFIR constructs, community capacity domains, and the five constructs of CI. RESULTS: Key findings include the need for shortened meeting times for meaningful engagement, opportunities for organizations to take on more active roles in the Collaboration, and enhanced community context expertise (i.e., those with lived experience) in all Collaboration initiatives. We identified additional elements to the core constructs of CI that are necessary for successful implementation: distinct role identification for partner organizations and incorporation of equity and inclusivity into collaboration processes and procedures. CONCLUSIONS: Results from this implementation evaluation provide valuable insights into implementation fidelity, participant experience, and implementation reach of an innovative, systems-level program. Findings demonstrate the context and requirements needed to successfully implement this innovative program approach and CI overall. Additional core elements for CI are identified and contribute to the growing body of literature on successful CI initiatives.

A program evaluation of the Innovative Teen Pregnancy Prevention Programs (iTP3) Project.

BACKGROUND: Teen pregnancy prevention in the United States has traditionally focused on the development, testing, and subsequent implementation of a set of evidence-based programs (EBPs), recommended nationally. However, these existing EBPs often do not prioritize the most at-risk or vulnerable populations. METHODS: The Innovative Teen Pregnancy Prevention Programs (iTP3) project was funded to facilitate the development of new, innovative programs to reach disparate populations. Through a mixed methods design, iTP3 evaluated the process and resulting innovative programs from five iterative cohorts of funded organizations, referred to as Innovators. iTP3 utilized both a traditional funding model with more traditional methods of capacity building assistance, but transitioned over time to a design-focused funding model in which organizations and individuals developed innovative programs through an intensive human centered design process. RESULTS: Evaluation results showed that the resulting portfolio of programs had differences in the types of programs resulting from the differing funding models. Notable differences among programs from the two funding models include program length, along with personnel, time, and resources needed to develop and manage. CONCLUSION: Both traditional and design funding models led to innovative programs, with notable differences in the development process and resulting programs.

School-Level Efforts to Address Sexual Health and Risky Sexual Behavior Among Students in Texas Alternative High Schools.

We compared sexual/reproductive health services and sexuality education topics provided in Texas alternative high schools (AHSs) with the prevalence of sexual risk behaviors among students in AHS. Using cross-sectional data from convenience samples of 14 principals, 14 lead health educators, and 515 students, we calculated descriptive statistics for 20 services and 15 sexuality education topics provided by AHSs and seven sexual risk behaviors among students in AHS. AHSs provided few sexual/reproductive health services and limited educational content, despite high levels of sexual risk taking among students. For example, no AHSs taught students about proper condom use, yet 84% of students have had sex. Findings provide preliminary evidence of unmet needs for school-based sexual/reproductive health services and comprehensive sexuality education in AHS settings. Future investigation with larger, representative samples is needed to assess the provision of sexual/reproductive health services and sexuality education in AHSs and monitor sexual risk behaviors in the AHS population.

Cross-sectional associations between domain-specific sitting time and other lifestyle health behaviours: the Stormont study.

BACKGROUND: There is a dearth of literature on how different domains of sitting time relate to other health behaviours. Therefore, this study aimed to explore these associations in a sample of office workers. METHODS: 7170 Northern Irish Civil Servants completed an online survey which included information on workday and non-workday sitting time in five domains (travel, work, TV, computer-use, leisure-time), physical activity, fruit and vegetable intake, alcohol consumption and cigarette smoking. An unhealthy behaviour score was calculated by summing the number of health behaviours which did not meet the current guidelines. Multinomial regressions examined associations between unhealthy behaviour score and each domain of sitting time. RESULTS: ≥7 hours sitting at work and ≥2 hours TV viewing on a workday both more than doubled the odds of partaking in ≥3 unhealthy behaviours [Odds ratio, OR = 2.03, 95% CI, (1.59-2.61); OR = 2.19 (1.71-2.80)] and ≥3 hours of TV viewing on a non-workday nearly tripled the odds [OR = 2.96 (2.32-3.77)]. CONCLUSIONS: High sitting time at work and TV viewing on a workday and non-workday are associated with increased odds of partaking in multiple unhealthy behaviours. Interventions need to focus on these domains and public health policy should consider sitting time as an important health behaviour.

Activation of α7 nicotinic acetylcholine receptor ameliorates HIV-associated neurology and neuropathology.

HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy are primarily manifested as impaired behaviours, glial activation/neuroinflammation and compromised neuronal integrity, for which there are no effective treatments currently available. In the current study, we used doxycycline-inducible astrocyte-specific HIV Tat transgenic mice (iTat), a surrogate HAND model, and determined effects of PNU-125096, a positive allosteric modulator of α7 nicotinic acetylcholine receptor (α7 nAChR) on Tat-induced behavioural impairments and neuropathologies. We showed that PNU-125096 treatment significantly improved locomotor, learning and memory deficits of iTat mice while inhibited glial activation and increased PSD-95 expression in the cortex and hippocampus of iTat mice. Using α7 nAChR knockout mice, we showed that α7 nAChR knockout eliminated the protective effects of PNU-125096 on iTat mice. In addition, we showed that inhibition of p38 phosphorylation by SB239063, a p38 MAPK-specific inhibitor exacerbated Tat neurotoxicity in iTat mice. Last, we used primary mouse cortical individual cultures and neuron-astrocytes co-cultures and in vivo staining of iTat mouse brain tissues and showed that glial activation was directly involved in the interplay among Tat neurotoxicity, α7 nAChR activation and the p38 MAPK signalling pathway. Taken together, these findings demonstrated for the first time that α7 nAChR activation led to protection against HAND and suggested that α7 nAChR modulator PNU-125096 holds significant promise for development of therapeutics for HAND.

Social-Ecological Barriers to Access to Healthcare for Adolescents: A Scoping Review.

Access to healthcare for adolescents is often overlooked in the United States due to federal and state-sponsored insurance programs such as Medicaid and the Children's Health Insurance Program. While these types of programs provide some relief, the issue of healthcare access goes beyond insurance coverage and includes an array of ecological factors that hinder youths from receiving services. The purpose of this scoping review was to identify social-ecological barriers to adolescents' healthcare access and utilization in the United States. We followed the PRISMA and scoping review methodological framework to conduct a comprehensive literature search in eight electronic databases for peer-reviewed articles published between 2010 and 2020. An inductive content analysis was performed to thematize the categories identified in the data extraction based on the Social-Ecological Model (SEM). Fifty studies were identified. Barriers across the five SEM levels emerged as primary themes within the literature, including intrapersonal-limited knowledge of and poor previous experiences with healthcare services, interpersonal-cultural and linguistic barriers, organizational-structural barriers in healthcare systems, community-social stigma, and policy-inadequate insurance coverage. Healthcare access for adolescents is a systems-level problem requiring a multifaceted approach that considers complex and adaptive behaviors.

Single-shot transient absorption spectroscopy techniques and design principles.

Single-shot transient absorption (SSTA) spectroscopy is fundamentally identical to transient absorption (TA) spectroscopy but differs in its implementation to enable the measurement of sample response at a range of pump-probe time delays in a single laser shot. As in TA, a pump pulse in SSTA photoexcites a sample, inducing a change in the absorption of a probe pulse. Both commercial and home-built TA instruments typically execute serial measurements at a range of pump-probe time delays to yield transients that report on the dynamics of the photoexcited species, with the sample returning to the same relaxed state between each measurement. SSTA instruments acquire a range of pump-probe time delays simultaneously by somehow encoding the time delay into the profile of the probe beam. This dramatically reduces the time required for SSTA measurements, enabling the measurement of unstable systems undergoing irreversible processes that cannot be accurately characterized using typical TA instruments. The implementation of the encoded time delay must be appropriately designed and carefully calibrated to suit the targeted system and ensure accurate measurements. This review describes techniques used to encode the time delay and design principles for SSTA instruments. Strategies are presented to implement a broadband probe, account for spatial variations in pump and probe beam profiles that influence the intensity and noise of the spatially encoded signal, optimize detection, and correct for dynamic background signals. With these design principles in place, SSTA is capable of measuring an array of unstable and evolving systems that cannot be addressed using typical TA instruments.

Self-Perceptions and Factors Associated With Being Put Down at School Among Middle and High School Students.

This study assessed the prevalence of verbally being put down by others and intrapersonal and normative factors associated with being put down by others among middle and high school students. Students (N = 1,027) completed the Adolescent Health Risk Behavior Survey. Over 16% of participants reported being put down at school. Students who identified with the negative words confused, unattractive, dull, and careless and identified less with the positive words popular, smart, considerate, cool, and self-confident reported being put down by others. High school students were less likely to be put down. As students scored higher on the Negative Self-Description Scale, their odds of being put down increased. As students scored higher on the Positive Self-Description Scale, their odds of being put down decreased. Students who perceived their friends drinking alcohol regularly were less likely to be put down. Strategies to enhance self-perceptions to raise self-awareness and form healthy/positive identities are needed.