Towards Harmonized Adolescent Health Measurement: Assessing Alignment Between Current Recommendations and the Global Action for Measurement of Adolescent Health-Recommended Indicators.

PURPOSE: This study identified alignment of indicators across different initiatives and data collection instruments as a foundation for future harmonization of adolescent health measurement. METHODS: Using the Global Action for Measurement of Adolescent health (GAMA) recommended indicators as the basis for comparison, we conducted a desk review of 14 global-level initiatives, such as the Sustainable Development Goals and the Global Strategy for Women's, Children's and Adolescents' Health, and five multicountry survey programs, such as the Multiple Indicator Cluster Surveys and the Global school-based Student Health Survey. We identified initiative and survey indicators similar to a GAMA indicator, deconstructed indicators into standard elements to facilitate comparison, and assessed alignment to the corresponding GAMA indicator across each of the elements. RESULTS: A total of 144 initiative indicators and 90 survey indicators were identified. Twenty-four initiative indicators (17%) and 14 survey indicators (16%) matched the corresponding GAMA indicators across all elements. Population of interest was the most commonly discrepant element; whereas GAMA indicators mostly refer to ages 10-19, many survey and initiative indicators encompass only part of this age range, for example, 15-19-year-olds as a subset of adults ages 15-49 years. An additional 53 initiative indicators (39%) and 44 survey indicators (49%) matched on all elements except the population of interest. DISCUSSION: The current adolescent measurement landscape is inconsistent, with differing recommendations on what and how to measure. Findings from this study support efforts to promote indicator alignment and harmonization across adolescent health measurement stakeholders at the global, regional, and country levels.

Indicators to Measure Adolescent Health at the Country, Regional, and Global Levels: Results of a Five-Year Selection Process by the Global Action for the Measurement of Adolescent Health.

PURPOSE: To improve adolescent health measurement, the Global Action for the Measurement of Adolescent health (GAMA) Advisory Group was formed in 2018 and published a draft list of 52 indicators across six adolescent health domains in 2022. We describe the process and results of selecting the adolescent health indicators recommended by GAMA (hereafter, "GAMA-recommended indicators"). METHODS: Each indicator in the draft list was assessed using the following inputs: (1) availability of data and stakeholders' perceptions on their relevance, acceptability, and feasibility across selected countries; (2) alignment with current measurement recommendations and practices; and (3) data in global databases. Topic-specific working groups comprised of GAMA experts and representatives of United Nations partner agencies reviewed results and provided preliminary recommendations, which were appraised by all GAMA members and finalized. RESULTS: There are 47 GAMA-recommended indicators (36 core and 11 additional) for adolescent health measurement across six domains: policies, programs, and laws (4 indicators); systems performance and interventions (4); health determinants (7); health behaviors and risks (20); subjective well-being (2); and health outcomes and conditions (10). DISCUSSION: These indicators are the result of a robust and structured five-year process to identify a priority set of indicators with relevance to adolescent health globally. This inclusive and participatory approach incorporated inputs from a broad range of stakeholders, including adolescents and young people themselves. The GAMA-recommended indicators are now ready to be used to measure adolescent health at the country, regional, and global levels.

Exploring a Preliminary Set of Indicators to Measure Adolescent Health: Results From a 12-Country Feasibility Study.

PURPOSE: To explore data availability, perceived relevance, acceptability and feasibility of implementing 52 draft indicators for adolescent health measurement in different countries globally. METHODS: A mixed-methods, sequential explanatory study was conducted in 12 countries. An online spreadsheet was used to assess data availability and a stakeholder survey to assess perceived relevance, acceptability, and feasibility of implementing each draft indicator proposed by the Global Action for Measurement of Adolescent health (GAMA). The assessments were discussed in virtual meetings with all countries and in deep dives with three countries. Findings were synthesized using descriptive statistics and qualitative thematic analysis. RESULTS: Data availability varied across the 52 draft GAMA indicators and across countries. Nine countries reported measuring over half of the indicators. Most indicators were rated relevant by stakeholders, while some were considered less acceptable and feasible. The ten lowest-ranking indicators were related to mental health, sexual health and substance use; the highest-ranking indicators centered on broader adolescent health issues, like use of health services. Indicators with higher data availability and alignment with national priorities were generally considered most relevant, acceptable and feasible. Barriers to measurement included legal, ethical and sensitivity issues, challenges with multi-sectoral coordination and data systems flexibility. DISCUSSION: Most of the draft GAMA indicators were deemed relevant and feasible, but contextual priorities and perceived acceptability influenced their implementation in countries. To increase their use for a more comprehensive understanding of adolescent health, better multi-sectoral coordination and tailored capacity building to accommodate the diverse data systems in countries will be required.

Time-resolved X-ray diffraction diagnostic development for the National Ignition Facility.

We present the development of an experimental platform that can collect four frames of x-ray diffraction data along a single line of sight during laser-driven, dynamic-compression experiments at the National Ignition Facility. The platform is comprised of a diagnostic imager built around ultrafast sensors with a 2-ns integration time, a custom target assembly that serves also to shield the imager, and a 10-ns duration, quasi-monochromatic x-ray source produced by laser-generated plasma. We demonstrate the performance with diffraction data for Pb ramp compressed to 150 GPa and illuminated by a Ge x-ray source that produces ∼7 × 1011, 10.25-keV photons/ns at the 400 µm diameter sample.

Developing a platform for Fresnel diffractive radiography with 1 µm spatial resolution at the National Ignition Facility.

An x-ray Fresnel diffractive radiography platform was designed for use at the National Ignition Facility. It will enable measurements of micron-scale changes in the density gradients across an interface between isochorically heated warm dense matter materials, the evolution of which is driven primarily through thermal conductivity and mutual diffusion. We use 4.75 keV Ti K-shell x-ray emission to heat a 1000 µm diameter plastic cylinder, with a central 30 µm diameter channel filled with liquid D2, up to 8 eV. This leads to a cylindrical implosion of the liquid D2 column, compressing it to ∼2.3 g/cm3. After pressure equilibration, the location of the D2/plastic interface remains steady for several nanoseconds, which enables us to track density gradient changes across the material interface with high precision. For radiography, we use Cu He-α x rays at 8.3 keV. Using a slit aperture of only 1 µm width increases the spatial coherence of the source, giving rise to significant diffraction features in the radiography signal, in addition to the refraction enhancement, which further increases its sensitivity to density scale length changes at the D2/plastic interface.

Increased Ion Temperature and Neutron Yield Observed in Magnetized Indirectly Driven D_{2}-Filled Capsule Implosions on the National Ignition Facility.

The application of an external 26 Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45 MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be ∼4.9 kT using the 14.1 MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30 kV pulsed-power system to deliver a ∼3 µs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment.

Modestly Increased Incidence of Ketosis in Caloric Restriction Does not Significantly Alter the Effects of Caloric Restriction.

OBJECTIVES: Caloric restriction (CR) has been shown to slow the aging processes in a number of preclinical studies and reduces expression of aging-associated biomarkers in human trials. We hypothesized that CR would lead to increased incidence of ketosis and that ketosis in CR individuals would alter the aging-protective effects of CR or biomarkers thereof. DESIGN/SETTING/PARTICIPANTS: We analyzed data from the "Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE, Phase 2)" Public Use Database available at calerie.duke.edu. In this study, non-obese adults between the ages of 21 and 50 were randomized to 25% CR or control (ad lib) diet groups and extensively monitored for two years. Given our focus on the effect of caloric restriction on ketosis, individuals with detectible ketones during the baseline visit (pre-randomization) and those with missing data for ketone testing were excluded from the analysis, leaving 71 control and 117 CR participants. MEASUREMENTS: We analyzed the incidence of ketosis as well as ketosis free survival in control and CR participants and assessed the effect of ketosis on a number of clinical lab values, functional assessments, and participant survey data related to aging biology. RESULTS: We report that CR was associated with modestly increased incidence of ketosis (4.4% in CR vs 1.9% in control), though CR-associated changes in T3, VO2, SUMPT-WT (weight normalized composite strength score - peak torque), physical functioning, and general health did not appear to be altered by the presence or absence of ketosis. Additional observations of interest include: 1) striking patterns of biomarker expression changes (MCP-1, TNFα, TGF-ß1, GH) in both the control and CR participants between the baseline visit and the 24-month post-randomization visit and 2) pro-growth/anti-inflammatory baseline (pre-randomization) biomarker expression profile in CR individuals that later test ketone positive relative to other CR individuals. CONCLUSIONS: CR modestly increases the incidence of ketosis in healthy adults, yet the increase in ketosis in CR patients did not significantly affect the aging-protective effects of CR. However, given the relatively small number of participants who were ketone positive, further investigation in larger study cohorts is still required for definitive conclusions.

Building capacity to facilitate policy implementation: A short course in adolescent and youth health in South Africa.

In order to respond more effectively to the health of young people in South Africa, in 2017 the National Department of Health of South Africa released the National Adolescent & Youth Health Policy. The Policy focused on a range of health problems and recommended interventions for delivery through multiple settings and government departments. It also included specific recommendations to empower and involve young people in policy and programme implementation. Adaptation of a short course on adolescent health in lowand middle-income countries, organized annually by the London School of Hygiene and Tropical Medicine and the World Health Organization, was piloted in 2017 as one means of contributing to the implementation of the Policy. The Adolescent & Youth Health Policy short course was subsequently offered in 2018 and 2019, attracting 96 participants working on adolescent health in various organizations at national and provincial levels throughout the country. Most participants (75%) successfully completed the course, as assessed by the completion criteria that had been defined. The range of topics for the assignments selected by the participants over the 3 years reflected both the content and intent of the Policy. The evaluations of the short course indicate that it helped to create legitimacy and strengthen the capacity of various constituencies, both of which are important prerequisites for policy implementation.

Development of an Aptamer-Based Electrochemical Microfluidic Device for Viral Vaccine Quantitation.

Global deployment of vaccines poses significant challenges in the distribution and use of the accompanying immunoassays, one of the standard methods for quality control of vaccines, particularly when establishing assays in countries worldwide to support testing/release upon importation. This work describes our effort toward developing an integrated, portable device to carry out affinity assays for viral particles quantification in viral vaccines by incorporating (i) aptamers, (ii) microfluidic devices, and (iii) electrochemical detection. We generated and characterized more than eight aptamers against multiple membrane proteins of cytomegalovirus (CMV), which we used as a model system and designed and fabricated electrochemical microfluidic devices to measure CMV concentrations in a candidate vaccine under development. The aptamer-based assays provided a half maximal effective concentration, EC50, of 12 U/mL, comparable to that of an ELISA using a pair of antibodies (EC50 60 U/mL). The device measured relative CMV concentrations accurately (within ±10% bias) and precisely (11%, percent relative standard deviation). This work represents the critical first steps toward developing simple, affordable, and robust affinity assays for global deployment without the need for sensitive equipment and extensive analyst training.

Trade-offs between succulent and non-succulent epiphytes underlie variation in drought tolerance and avoidance.

Epiphyte communities comprise important components of many forest ecosystems in terms of biomass and diversity, but little is known regarding trade-offs that underlie diversity and structure in these communities or the impact that microclimate has on epiphyte trait allocation. We measured 22 functional traits in vascular epiphyte communities across six sites that span a microclimatic gradient in a tropical montane cloud forest region in Costa Rica. We quantified traits that relate to carbon and nitrogen allocation, gas exchange, water storage, and drought tolerance. Functional diversity was high in all but the lowest elevation site where drought likely limits the success of certain species with particular trait combinations. For most traits, variation was explained by relationships with other traits, rather than differences in microclimate across sites. Although there were significant differences in microclimate, epiphyte abundance, and diversity, we found substantial overlap in multivariate trait space across five of the sites. We found significant correlations between functional traits, many of which related to water storage (leaf water content, leaf thickness, hydrenchymal thickness), drought tolerance (turgor loss point), and carbon allocation (specific leaf area, leaf dry matter content). This suite of trait correlations suggests that the epiphyte community has evolved functional strategies along with a drought avoidance versus drought tolerance continuum where leaf succulence emerged as a pivotal overall trait.

A call for standardised age-disaggregated health data.

The 2030 Sustainable Development Goals agenda calls for health data to be disaggregated by age. However, age groupings used to record and report health data vary greatly, hindering the harmonisation, comparability, and usefulness of these data, within and across countries. This variability has become especially evident during the COVID-19 pandemic, when there was an urgent need for rapid cross-country analyses of epidemiological patterns by age to direct public health action, but such analyses were limited by the lack of standard age categories. In this Personal View, we propose a recommended set of age groupings to address this issue. These groupings are informed by age-specific patterns of morbidity, mortality, and health risks, and by opportunities for prevention and disease intervention. We recommend age groupings of 5 years for all health data, except for those younger than 5 years, during which time there are rapid biological and physiological changes that justify a finer disaggregation. Although the focus of this Personal View is on the standardisation of the analysis and display of age groups, we also outline the challenges faced in collecting data on exact age, especially for health facilities and surveillance data. The proposed age disaggregation should facilitate targeted, age-specific policies and actions for health care and disease management.

Machine learning guided aptamer refinement and discovery.

Aptamers are single-stranded nucleic acid ligands that bind to target molecules with high affinity and specificity. They are typically discovered by searching large libraries for sequences with desirable binding properties. These libraries, however, are practically constrained to a fraction of the theoretical sequence space. Machine learning provides an opportunity to intelligently navigate this space to identify high-performing aptamers. Here, we propose an approach that employs particle display (PD) to partition a library of aptamers by affinity, and uses such data to train machine learning models to predict affinity in silico. Our model predicted high-affinity DNA aptamers from experimental candidates at a rate 11-fold higher than random perturbation and generated novel, high-affinity aptamers at a greater rate than observed by PD alone. Our approach also facilitated the design of truncated aptamers 70% shorter and with higher binding affinity (1.5 nM) than the best experimental candidate. This work demonstrates how combining machine learning and physical approaches can be used to expedite the discovery of better diagnostic and therapeutic agents.

The Political, Research, Programmatic, and Social Responses to Adolescent Sexual and Reproductive Health and Rights in the 25 Years Since the International Conference on Population and Development.

Among the ground-breaking achievements of the International Conference on Population and Development (ICPD) was its call to place adolescent sexual and reproductive health (ASRH) on global health and development agendas. This article reviews progress made in low- and middle-income countries in the 25 years since the ICPD in six areas central to ASRH-adolescent pregnancy, HIV, child marriage, violence against women and girls, female genital mutilation, and menstrual hygiene and health. It also examines the ICPD's contribution to the progress made. The article presents epidemiologic levels and trends; political, research, programmatic and social responses; and factors that helped or hindered progress. To do so, it draws on research evidence and programmatic experience and the expertise and experiences of a wide number of individuals, including youth leaders, in numerous countries and organizations. Overall, looking across the six health topics over a 25-year trajectory, there has been great progress at the global and regional levels in putting adolescent health, and especially adolescent sexual and reproductive health and rights, higher on the agenda, raising investment in this area, building the epidemiologic and evidence-base, and setting norms to guide investment and action. At the national level, too, there has been progress in formulating laws and policies, developing strategies and programs and executing them, and engaging communities and societies in moving the agenda forward. Still, progress has been uneven across issues and geography. Furthermore, it has raced ahead sometimes and has stalled at others. The ICPD's Plan of Action contributed to the progress made in ASRH not just because of its bold call in 1994 but also because it provided a springboard for advocacy, investment, action, and research that remains important to this day.

A Package of Sexual and Reproductive Health and Rights Interventions-What Does It Mean for Adolescents?

This article analyzes the relevance of the comprehensive definition of sexual and reproductive health and rights (SRHR) to adolescents and identifies adolescent-specific implications for the implementation of an essential package of SRHR interventions. The delivery of a comprehensive approach to SRHR targeting adolescents is underpinned by five principles-equity, quality, accountability, multisectorality, and meaningful engagement. All SRHR interventions included in the package are relevant to adolescents, given the diversity of adolescents' SRHR needs and considering their specific attributes, circumstances, and experiences. Ensuring that this package is available, accessible, and acceptable to adolescents requires an approach that looks at adolescents as being biologically and socially distinct from other age groups and acknowledges that they face some specific barriers when accessing SRHR services. This article provides cross-cutting strategies for the implementation of a comprehensive approach to SRHR for adolescents and specific considerations in delivering each intervention in the package of essential SRHR interventions. To further implement the International Conference on Population and Development Programme of Action, a prerequisite for achieving the Sustainable Development Goals, SRHR interventions must be adolescent responsive, delivered through multiple platforms, leveraging multisectoral collaboration, and strengthening accountability and participation.

Forward, Together: A Collaborative Path to Comprehensive Adolescent Sexual and Reproductive Health and Rights in Our Time.

The 1994 International Conference on Population and Development established a basis for the advancement of adolescent sexual and reproductive health and rights (ASRHR) that endures today. Twenty-five years later, our vision for the future warrants reflection based on a clear understanding of the opportunities and challenges before us. Inclusion of adolescents on global, regional, and national agendas; increased investment in ASRHR policies and programs; renewed commitments to universal health coverage; increased school enrollment; and advances in technology are all critical opportunities we can and must leverage to catalyze progress for adolescents. At the same time, a range of significant challenges remain, have newly emerged, or can be seen on the horizon, including persistent denial of adolescent sexuality; entrenched gender inequality; resistance to meaningfully engaging adolescents and young people in political and programmatic processes; weak systems, integration, and multisectoral coordination; changes in population dynamics; humanitarian and climate crises; and changes in family and community structures. To achieve as much progress toward our vision for ASRHR as possible, the global ASRHR community must take strategic and specific steps in the next 10 years within five areas for action: (1) mobilize and make full use of political and social support for ASRHR policies and programs; (2) increase and make effective use of external and domestic funding for ASRHR; (3) develop, communicate, apply, and monitor enabling and protective laws and policies for ASRHR; (4) use and improve available ASRHR data and evidence to strengthen advocacy, policies, and programs; and (5) manage the implementation of ASRHR strategies at scale with quality and equity.

Making Implementation Science Work for Children and Adolescents Living With HIV.

The global HIV response is leaving children and adolescents behind. Because of a paucity of studies on treatment and care models for these age groups, there are gaps in our understanding of how best to implement services to improve their health outcomes. Without this evidence, policymakers are left to extrapolate from adult studies, which may not be appropriate, and can lead to inefficiencies in service delivery, hampered uptake, and ineffective mechanisms to support optimal outcomes. Implementation science research seeks to investigate how interventions known to be efficacious in study settings are, or are not, routinely implemented within real-world programmes. Effective implementation science research must be a collaborative effort between government, funding agencies, investigators, and implementers, each playing a key role. Successful implementation science research in children and adolescents requires clearer policies about age of consent for services and research that conform to ethical standards but allow for rational modifications. Implementation research in these age groups also necessitates age-appropriate consultation and engagement of children, adolescents, and their caregivers. Finally, resource, systems, technology, and training must be prioritized to improve the availability and quality of age-/sex-disaggregated data. Implementation science has a clear role to play in facilitating understanding of how the multiple complex barriers to HIV services for children and adolescents prevent effective interventions from reaching more children and adolescents living with HIV, and is well positioned to redress gaps in the HIV response for these age groups. This is truer now more than ever, with urgent and ambitious 2020 global targets on the horizon and insufficient progress in these age groups to date.