Allostatic Load in Childhood, Adolescence, and Young Adulthood: Are Assumptions of Measurement Invariance Warranted?

OVERVIEW: Allostatic load represents the cumulative toll of chronic mobilization of the body's stress response systems, as indexed by biomarkers. Higher levels of stress and disadvantage predict higher levels of allostatic load, which, in turn, predict poorer physical and mental health outcomes. To maximize the efficacy of prevention efforts, screening for stress- and disadvantage-associated health conditions must occur before middle age-that is, during childhood, adolescence, and young adulthood. However, this requires that models of allostatic load display properties of measurement invariance across age groups. Because most research on allostatic load has featured older adults, it is unclear if these requirements can be met. METHODS: To address this question, we fit a series of exploratory and confirmatory analytic models to data on eight biomarkers using a nationally representative sample of N = 4260 children, adolescents, and young adults drawn from the National Health and Nutrition Examination Survey dataset. RESULTS: Exploratory and confirmatory models indicated that, consistent with allostatic load theory, a unidimensional model was a good fit to the data. However, this model did not display properties of measurement invariance; post-hoc analyses suggested that the biomarkers included in the final confirmatory model were most strongly intercorrelated among young adults and most weakly intercorrelated among adolescents. CONCLUSIONS: These results underscore the importance of testing assumptions about measurement invariance in allostatic load before drawing substantive conclusions about stress, disadvantage, and health by directly comparing levels of allostatic load across different stages of development, while underscoring the need to expand investigations of measurement invariance to samples of longitudinal data.

Enhancing Human-Centered Design With Youth-Led Participatory Action Research Approaches for Adolescent Sexual and Reproductive Health Programming.

Existing participatory research approaches have failed to identify innovative methods that overcome the persistent barriers to adolescent sexual and reproductive health service demand and access. Increasingly, programmers have turned to human-centered design (HCD), a problem-solving process that centers the needs, perspectives, and experiences of people, when developing solutions to complex SRH challenges. This article describes the application of a youth-engaged version of HCD as part of Adolescents 360, a transdisciplinary initiative to increase 15- to 19-year-old girls' use of modern contraception in Nigeria, Ethiopia, and Tanzania. Youth-adult design teams (including 111 "youth designers" trained in HCD methods) undertook formative research to inform the design and implementation of interventions. We reflect on the practical implications of using instrumental strategies of HCD with a youth-led participatory approach. Our experience indicates that (1) engaging youth as project partners in transdisciplinary teams requires planned and dedicated financial and human resources; (2) involving youth as action researchers can help identify opportunities to improve program empathy and responsiveness; (3) it is difficult to recruit "extreme users" as project partners because of the high competencies needed in HCD; (4) centering empathy and employing design standards during prototyping can drive decision-making and resolve questions raised by conflicting evidence claims in existing bodies of literature; and (5) testing tangible services and products in real-world settings continues long after the intervention design phase. Youth-adult partnership should continue throughout this iterative and adaptive phase to ensure that the adolescent experience of the intervention remains at the core of intervention delivery.

Deconstructing Cumulative Risk: Poverty and Aspects of Instability Relate Uniquely to Young Children's Basal Cortisol.

This study deconstructs cumulative risk to probe unique relations to basal cortisol for family income and four distinct aspects of poverty-related instability. Participants were 288 children aged 3-5 years who attended Head Start preschool. Parents reported on poverty risks. Children provided samples of salivary cortisol at four times of day on 6 days. Results of hierarchical linear modeling with piecewise latent growth curves representing basal cortisol indicated unique relations for family income, household chaos, neighborhood risk, attachment-disruptive residential changes, and non-attachment changes. The findings support an equifinality implied by cumulative risk models in demonstrating that multiple risks relate to cortisol dysregulation yet also suggest the utility of considering unique effects of different risks for neurophysiological stress response functioning.

The potential for citizen science to produce reliable and useful information in ecology.

We examined features of citizen science that influence data quality, inferential power, and usefulness in ecology. As background context for our examination, we considered topics such as ecological sampling (probability based, purposive, opportunistic), linkage between sampling technique and statistical inference (design based, model based), and scientific paradigms (confirmatory, exploratory). We distinguished several types of citizen science investigations, from intensive research with rigorous protocols targeting clearly articulated questions to mass-participation internet-based projects with opportunistic data collection lacking sampling design, and examined overarching objectives, design, analysis, volunteer training, and performance. We identified key features that influence data quality: project objectives, design and analysis, and volunteer training and performance. Projects with good designs, trained volunteers, and professional oversight can meet statistical criteria to produce high-quality data with strong inferential power and therefore are well suited for ecological research objectives. Projects with opportunistic data collection, little or no sampling design, and minimal volunteer training are better suited for general objectives related to public education or data exploration because reliable statistical estimation can be difficult or impossible. In some cases, statistically robust analytical methods, external data, or both may increase the inferential power of certain opportunistically collected data. Ecological management, especially by government agencies, frequently requires data suitable for reliable inference. With standardized protocols, state-of-the-art analytical methods, and well-supervised programs, citizen science can make valuable contributions to conservation by increasing the scope of species monitoring efforts. Data quality can be improved by adhering to basic principles of data collection and analysis, designing studies to provide the data quality required, and including suitable statistical expertise, thereby strengthening the science aspect of citizen science and enhancing acceptance by the scientific community and decision makers.

Potencial de la Ciencia Ciudadana para Producir Información Útil y Confiable en la Ecología Resumen Examinamos las características de la ciencia ciudadana que influyen sobre la calidad de datos, el poder inferencial, y la utilidad en la ecología. Consideramos temas como el muestreo ecológico (basado en probabilidad, deliberado, oportunista), la conexión entre la técnica de muestreo y la inferencia estadística (basada en diseño, basada en modelo) y los paradigmas científicos (confirmatorio, exploratorio) como trasfondo contextual para nuestra evaluación. Distinguimos varios tipos de investigación de ciencia ciudadana, desde investigación intensiva con protocolos rigurosos enfocados en preguntas claramente articuladas hasta proyectos de participación masiva en plataformas de internet con recolección de datos oportunistas carentes de un diseño de muestreo, y examinamos los objetivos generales, el diseño, el análisis, y la preparación de los voluntarios y el desempeño. Identificamos características clave que influyen sobre la calidad de los datos: los objetivos del proyecto, el diseño y el análisis, y la preparación y el desempeño de los voluntarios. Los proyectos con buenos diseños, voluntarios preparados, y supervisión profesional pueden cumplir con criterios estadísticos para producir datos de alta calidad con un fuerte poder inferencial, y por lo tanto son muy adecuados para los objetivos de investigación ecológica. Los proyectos con una recolección oportunista de datos, un diseño de muestreo ínfimo o nulo, y una preparación mínima de los voluntarios son más adecuados para los objetivos generales relacionados con la educación pública o la exploración de datos ya que la estimación estadística confiable puede ser complicada o imposible. En algunos casos los métodos analíticos estadísticamente sólidos, los datos externos, o ambos, pueden incrementar el poder inferencial de ciertos datos recolectados de manera oportunista. El manejo ecológico, en especial el que realizan las agencias gubernamentales, requiere frecuentemente de datos apropiados para una inferencia confiable. Con protocolos estandarizados, métodos analíticos modernos, y programas supervisados correctamente, la ciencia ciudadana puede contribuir de forma valiosa a la conservación al incrementar el alcance de los esfuerzos de monitoreo para una especie. La calidad de datos puede mejorarse si se adhiere a los principios básicos de la recolección y análisis de datos, se diseñan los estudios para que proporcionen la calidad requerida de datos, y si se incluye una pericia estadística adecuada, fortaleciendo así el aspecto científico de la ciencia ciudadana y aumentando su aceptación dentro de la comunidad científica y con quienes toman las decisiones.

Double-Loop Learning in Adaptive Management: The Need, the Challenge, and the Opportunity.

Adaptive management addresses uncertainty about the processes influencing resource dynamics, as well as the elements of decision making itself. The use of management to reduce both kinds of uncertainty is known as double-loop learning. Though much work has been done on the theory and procedures to address structural uncertainty, there has been less progress in developing an explicit approach for institutional learning about decision elements. Our objective is to describe evidence-based learning about the decision elements, as a complement to the formal "learning by doing" framework for reducing structural uncertainties. Adaptive management is described as a multi-phase approach to management and learning, with a set-up phase of identifying stakeholders, objectives, and other decision elements; an iterative phase that uses these elements in an ongoing cycle of technical learning about system structure and management impacts; and an institutional learning phase involving the periodic reconsideration of the decision elements. We describe a framework for institutional learning that is complementary to that of technical learning, including uncertainty metrics, propagation of change, and mechanisms and consequences of change over time. Operational issues include ways to recognize when the decision elements should be revisited, which elements should be adjusted, and how alternatives can be identified and incorporated based on experience and management performance. We discuss the application of this framework in decision making for renewable natural resources. As important as it is to learn about the processes driving resource dynamics, learning about the elements of the decision architecture is equally, if not more, important.

Crisis resolution and home treatment: stakeholders' views on critical ingredients and implementation in England.

BACKGROUND: Crisis resolution teams (CRTs) can provide effective home-based treatment for acute mental health crises, although critical ingredients of the model have not been clearly identified, and implementation has been inconsistent. In order to inform development of a more highly specified CRT model that meets service users' needs, this study used qualitative methods to investigate stakeholders' experiences and views of CRTs, and what is important in good quality home-based crisis care. METHOD: Semi-structured interviews and focus groups were conducted with service users (n = 41), carers (n = 20) and practitioners (CRT staff, managers and referrers; n = 147, 26 focus groups, 9 interviews) in 10 mental health catchment areas in England, and with international CRT developers (n = 11). Data were analysed using thematic analysis. RESULTS: Three domains salient to views about optimal care were identified. 1. The organisation of CRT care: Providing a rapid initial responses, and frequent home visits from the same staff were seen as central to good care, particularly by service users and carers. Being accessible, reliable, and having some flexibility were also valued. Negative experiences of some referral pathways, and particularly lack of staff continuity were identified as problematic. 2. The content of CRT work: Emotional support was at the centre of service users' experiences. All stakeholder groups thought CRTs should involve the whole family, and offer a range of interventions. However, carers often feel excluded, and medication is often prioritised over other forms of support. 3. The role of CRTs within the care system: Gate-keeping admissions is seen as a key role for CRTs within the acute care system. Service users and carers report that recovery is quicker compared to in-patient care. Lack of knowledge and misunderstandings about CRTs among referrers are common. Overall, levels of stakeholder agreement about the critical ingredients of good crisis care were high, although aspects of this were not always seen as achievable. CONCLUSIONS: Stakeholders' views about optimal CRT care suggest that staff continuity, carer involvement, and emotional and practical support should be prioritised in service improvements and more clearly specified CRT models.

Can the Arts Get Under the Skin? Arts and Cortisol for Economically Disadvantaged Children.

This within-subjects experimental study investigated the influence of the arts on cortisol for economically disadvantaged children. Participants were 310 children, ages 3-5 years, who attended a Head Start preschool and were randomly assigned to participate in different schedules of arts and homeroom classes on different days of the week. Cortisol was sampled at morning baseline and after arts and homeroom classes on two different days at start, middle, and end of the year. For music, dance, and visual arts, grouped and separately, results of piecewise hierarchical linear modeling with time-varying predictors suggested cortisol was lower after an arts versus homeroom class at middle and end of the year but not start of the year. Implications concern the impact of arts on cortisol for children facing poverty risks.

Men's perceptions of child-bearing and fertility control in Pakistan: insights from a PEER project.

Notions of masculinity, which promote the role of men as providers and decision-makers, alongside men's opposition to modern forms of contraception, have long been assumed to be a barrier to women's use of contraception in Pakistan. There has been little in-depth exploration of varieties of masculinity and how these may influence men's views of child-bearing or fertility preferences. This study used Participatory Ethnographic and Evaluation Research to explore married men's (aged 18 to 45 years) perceptions of marriage, child-bearing and fertility control. A total of 31 men were recruited as researchers in two provinces (Punjab and Khyber Pakhtunkhwa), who, in turn, each interviewed two male friends. Men overall supported a 'smaller' family size and use of contraceptive methods. Drivers of this preference included perceived economic constraints, the desire to invest in children's education, and wider acceptability of contraceptive use. Limiting family size was associated with both the value of competent male providers taking care of their children, as well as being poor. Men wanted to have better access to information through a range of channels. Understanding the sociocultural contexts in which masculinities are constructed is essential before involving men in family planning programmes, so that gender inequalities are not reinforced.

Female Genital Mutilation in Kenya: are young men allies in social change programmes?

The Girl Summit held in 2014 aimed to mobilise greater effort to end Female Genital Mutilation (FGM) within a generation, building on a global movement which viewed the practice as a severe form of violence against women and girls and a violation of their rights. The UN, among others, endorse "comprehensive" strategies to end FGM, including legalistic measures, social protection and social communications. FGM is a sensitive issue and difficult to research, and rapid ethnographic methods can use existing relations of trust within social networks to explore attitudes towards predominant social norms which posit FGM as a social necessity. This study used Participatory Ethnographic Evaluation Research (PEER) to understand young men's (18-25 years) perceptions of FGM, demand for FGM among future spouses, and perceptions of efforts to end FGM in a small town in West Pokot, Kenya, where FGM is reported to be high (between 85% to 96%). Twelve PEER researchers were recruited, who conducted two interviews with their friends, generating a total of 72 narrative interviews. The majority of young men who viewed themselves as having a "modern" outlook and with aspirations to marry "educated" women were more likely not to support FGM. Our findings show that young men viewed themselves as valuable allies in ending FGM, but that voicing their opposition to the practice was often difficult. More efforts are needed by multi-stakeholders - campaigners, government and local leaders - to create an enabling environment to voice that opposition.

Resilience and Resource Management.

Resilience is an umbrella concept with many different shades of meaning. The use of the term has grown over the past several decades to the point that by now, many disciplines have their own definitions and metrics. In this paper, we aim to provide a context and focus for linkages of resilience to natural resources management. We consider differences and similarities in resilience as presented in several disciplines relevant to resource management. We present a conceptual framework that includes environmental drivers, management interventions, and system responses cast in terms of system resilience, as well as a process for decision making that allows learning about system resilience through experience and incorporation of that learning into management. We discuss the current state of operational management for resilience, and suggest ways to improve it. Finally, we describe the challenges in managing for resilience and offer some recommendations about the scientific information needs and scientific issues relevant to making resilience a more meaningful component of natural resources management.

Adaptive management: from more talk to real action.

The challenges currently facing resource managers are large-scale and complex, and demand new approaches to balance development and conservation goals. One approach that shows considerable promise for addressing these challenges is adaptive management, which by now is broadly seen as a natural, intuitive, and potentially effective way to address decision-making in the face of uncertainties. Yet the concept of adaptive management continues to evolve, and its record of success remains limited. In this article, we present an operational framework for adaptive decision-making, and describe the challenges and opportunities in applying it to real-world problems. We discuss the key elements required for adaptive decision-making, and their integration into an iterative process that highlights and distinguishes technical and social learning. We illustrate the elements and processes of the framework with some successful on-the-ground examples of natural resource management. Finally, we address some of the difficulties in applying learning-based management, and finish with a discussion of future directions and strategic challenges.

Advancing clinical trial equity through integration of telehealth and decentralized treatment.

Innovative strategies to increase clinical trial accessibility and equity are needed. We conducted a retrospective review of a phase II investigator-initiated trial to determine whether the modification of clinical trial design to decentralize study treatment can improve trial accessibility among underrepresented groups. Sociodemographic characteristics, including area deprivation indices, as well as study site travel distance, time, and costs were compared between enrolled participants who received chemotherapy locally and participants who did not. Participants who received chemotherapy locally lived substantially farther from the study site (median = 95.90 vs 25.20 miles, P = .004), faced a greater time burden traveling to the study site (median = 115.00 vs 34.00 minutes, P = .002), and had higher travel-related costs for a single trip to the study site (median = $62.81 vs $16.51, P = .004). This study highlights opportunities for alleviating financial and time burdens associated with clinical trial participation, promoting equity in clinical research. Trial Registration: ClinicalTrials.gov identifier: NCT04380337.

Local origin of excitatory-inhibitory tuning equivalence in a cortical network.

The interplay between excitation and inhibition determines the fidelity of cortical representations. The receptive fields of excitatory neurons are often finely tuned to encoded features, but the principles governing the tuning of inhibitory neurons remain elusive. In this study, we recorded populations of neurons in the mouse postsubiculum (PoSub), where the majority of excitatory neurons are head-direction (HD) cells. We show that the tuning of fast-spiking (FS) cells, the largest class of cortical inhibitory neurons, was broad and frequently radially symmetrical. By decomposing tuning curves using the Fourier transform, we identified an equivalence in tuning between PoSub-FS and PoSub-HD cell populations. Furthermore, recordings, optogenetic manipulations of upstream thalamic populations and computational modeling provide evidence that the tuning of PoSub-FS cells has a local origin. These findings support the notion that the equivalence of neuronal tuning between excitatory and inhibitory cell populations is an intrinsic property of local cortical networks.

Development of a reference interval for urinary ammonia-to-creatinine ratio in feline patients.

BACKGROUND: Disruption of acid-base homeostasis can lead to many clinical problems. Ammonia excretion by the kidneys is critical to maintaining acid-base homeostasis through bicarbonate production. Measurement of ammonia excretion may help determine if the kidneys are properly functioning in maintaining acid-base balance. Reference intervals are essential tools for clinical decision-making but do not currently exist for urinary ammonia-to-creatinine ratio (UACR) in feline patients. OBJECTIVE: This study aimed to generate a reference interval (RI) for UACR in healthy adult cats. METHODS: The study used samples from client-owned adult healthy cats that presented to the University of Florida Primary Care and Dentistry service (n = 92). Physical examination, serum biochemistry, urinalysis, urine ammonia, and creatinine concentrations were measured. Cats were excluded if there were significant abnormalities in their urinalysis or biochemistry panel. The RI for UACR was calculated according to the recommendation of the American Society for Veterinary Clinical Pathology. The UACR was evaluated for correlation with serum bicarbonate, weight, age, and sex. RESULTS: The RI for UACR was 3.4-20.7 with 90% confidence intervals for the lower and upper limits of (3.0-3.7) and (16.0-23.7), respectively. No significant correlation with age, sex, or weight was found. There was no discernable relationship between serum bicarbonate and UACR. CONCLUSIONS: Establishing an RI for UACR in healthy adult cats will allow further studies to determine if changes in UACR are observed during specific disease states.

Personalized Accelerated ChEmoRadiation (PACER) for Lung Cancer: Protocol for a Bayesian Optimal Phase I/II Trial.

INTRODUCTION: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs). METHODS: Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy (RT) will be delivered to a total dose of 60 to 66 Gy in 30, 25, or 20 fractions depending on the ability to meet constraints to key organs at risk including the lungs, heart, and esophagus. The primary endpoint is high grade pulmonary, esophageal, or cardiac toxicity. A Bayesian optimized design is used to determine stopping boundaries and evaluate the primary endpoint. CONCLUSION: PACER will evaluate the safety and feasibility of personalized accelerated chemoradiotherapy for lung cancer.

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior.

Neural population dynamics relevant to behavior vary over multiple spatial and temporal scales across three-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type- and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible. We applied this method to resolve rapid dopamine release dynamics across the striatum, revealing distinct, modality-specific spatiotemporal patterns in response to salient sensory stimuli extending over millimeters of tissue. Targeted optogenetics enabled flexible control of neural signaling on multiple spatial scales, better matching endogenous signaling patterns, and the spatial localization of behavioral function across large circuits.

Four conservation challenges and a synthesis.

Conservation and management of biological systems involves decision-making over time, with a generic goal of sustaining systems and their capacity to function in the future. We address four persistent and difficult conservation challenges: (1) prediction of future consequences of management, (2) uncertainty about the system's structure, (3) inability to observe ecological systems fully, and (4) nonstationary system dynamics. We describe these challenges in terms of dynamic systems subject to different sources of uncertainty, and we present a basic Markovian framework that can encompass approaches to all four challenges. Finding optimal conservation strategies for each challenge requires issue-specific structural features, including adaptations of state transition models, uncertainty metrics, valuation of accumulated returns, and solution methods. Strategy valuation exhibits not only some remarkable similarities among approaches but also some important operational differences. Technical linkages among the models highlight synergies in solution approaches, as well as possibilities for combining them in particular conservation problems. As methodology and computing software advance, such an integrated conservation framework offers the potential to improve conservation outcomes with strategies to allocate management resources efficiently and avoid negative consequences.

Effect of Radiation Schedule on Transportation-Related Carbon Emissions: A Case Study in Rectal Cancer.

Purpose: The health care sector is a major contributor of worldwide greenhouse gas (GHG) emissions. Indirect emissions, including those associated with transportation, make up 82% of the US health care sector's environmental footprint. Radiation therapy (RT) treatment regimens present an opportunity for environmental health care-based stewardship owing to the high incidence of cancer diagnosis, significant utilization of RT, and myriad treatment days required for curative regimens. Because the use of short-course RT (SCRT) in the treatment of rectal cancer has demonstrated noninferior clinical outcomes compared with conventional, long-course RT (LCRT), we investigate the environmental and health equity-related outcomes. Methods and Materials: Patients treated with curative, preoperative RT for newly diagnosed rectal cancer at our institution between 2004 and 2022 and living in-state were included. Travel distance was estimated using patients' reported home address. Associated GHG emissions were calculated and reported in carbon dioxide equivalents (CO2e). Results: Of 334 patients included, the total distance traveled for the treatment course was significantly greater in patients treated with LCRT versus SCRT (median, 1417 vs 319 miles; P < .001). Total CO2e emissions for those undergoing LCRT (n = 261) and SCRT (n = 73) were 665.3 kg CO2e and 149.9 kg CO2e, respectively, per treatment course (P < .001), with a net difference of 515.4 kg CO2e. Relatively, this suggests that LCRT is associated with 4.5 times greater GHG emissions from patient transportation. Conclusions: Using treatment of rectal cancer as proof-of-principle, we advocate for the inclusion of environmental considerations in the creation of climate-resilient oncologic RT practices, especially in the context of equivocal clinical outcomes between RT fractionation schedules.

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior.

Neural population dynamics relevant for behavior vary over multiple spatial and temporal scales across 3-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array and imaging approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice. We developed a semi-automated micro-CT based strategy to precisely localize positions of each optical fiber. This highly-customizable approach enables investigation of multi-scale spatial and temporal patterns of cell-type and neurotransmitter specific signals over arbitrary 3-D volumes at a spatial resolution and coverage previously inaccessible. We applied this method to resolve rapid dopamine release dynamics across the striatum volume which revealed distinct, modality specific spatiotemporal patterns in response to salient sensory stimuli extending over millimeters of tissue. Targeted optogenetics through our fiber arrays enabled flexible control of neural signaling on multiple spatial scales, better matching endogenous signaling patterns, and spatial localization of behavioral function across large circuits.

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial.

Importance: Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy. Objective: To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control. Design, Setting, and Participants: This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3). Intervention: Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3. Main outcome: Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up. Results: In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects). Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials. Trial Registration: ClinicalTrials.gov Identifier: NCT01463423.