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OBJECTIVE: We compared the effectiveness and safety of polidocanol 1% endovenous microfoam ablation vs endovenous thermal ablation with radiofrequency or laser energy for treatment of venous insufficiency caused by lower extremity truncal vein incompetence via network meta-analysis of published comparative evidence. METHODS: We conducted a systematic literature review following best practices, including a prospective protocol. We screened studies published in English from 2000 to 2023 for randomized and nonrandomized studies reporting direct or indirect comparisons between polidocanol 1% endovenous microfoam and endovenous thermal ablation. Thirteen studies met our eligibility criteria for the network meta-analysis. The co-primary effectiveness outcomes were the closure rate ≥3 months after procedure and the average change in the Venous Clinical Severity Score. For the subgroup of venous ulcer patients, the ulcer healing rate was the primary effectiveness outcome. The secondary outcomes included safety and patient-reported outcomes. Network meta-analyses were conducted on outcomes having sufficient data. Categorical outcomes were summarized using odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity tests and estimates of network inconsistency were used to investigate the robustness of our meta-analysis. RESULTS: We found that polidocanol 1% endovenous microfoam was not significantly different statistically from endovenous thermal ablation for venous closure (OR, 0.65; 95% CI, 0.36-1.18; P = .16). Although not the primary aim of the study, the network meta-analysis also provided evidence to confirm our supposition that polidocanol 1% endovenous microfoam was significantly differentiated statistically from physician-compounded foam, with higher odds for vein closure (OR, 2.91; 95% CI, 1.58-5.37; P < .01). A sensitivity analysis using the longest available time point for closure in each study, with a minimum of 12 months of follow-up (median, 48 months; range, 12-72 months), showed results similar to those of the main analysis. No association was found between the risk of deep vein thrombosis and the treatment received. The available data were insufficient for a network meta-analysis of Venous Clinical Severity Score improvement and ulcer healing rates. CONCLUSIONS: Polidocanol 1% endovenous microfoam was not significantly different statistically from endovenous thermal ablation for venous closure and deep vein thrombosis risk for chronic venous insufficiency treatment, based on a network meta-analysis of published evidence. Polidocanol 1% endovenous microfoam was significantly differentiated statistically from physician-compounded foam, with higher odds of vein closure. A sensitivity analysis found venous closure findings were robust at follow-up intervals of 12 months or greater and for up to 6 years. New evidence meeting the inclusion criteria for this review will be incorporated at regular intervals into a living network meta-analysis.

Prostate cancer is frequently treated with radiotherapy. Unfortunately, aggressive radioresistant relapses can arise, and the molecular underpinnings of radioresistance are unknown. Modern clinical radiotherapy is evolving to deliver higher doses of radiation in fewer fractions (hypofractionation). We therefore analyzed genomic, transcriptomic, and proteomic data to characterize prostate cancer radioresistance in cells treated with both conventionally fractionated and hypofractionated radiotherapy. Independent of fractionation schedule, resistance to radiotherapy involved massive genomic instability and abrogation of DNA mismatch repair. Specific prostate cancer driver genes were modulated at the RNA and protein levels, with distinct protein subcellular responses to radiotherapy. Conventional fractionation led to a far more aggressive biomolecular response than hypofractionation. Testing preclinical candidates identified in cell lines, we revealed POLQ (DNA Polymerase Theta) as a radiosensitizer. POLQ-modulated radioresistance in model systems and was predictive of it in large patient cohorts. The molecular response to radiation is highly multimodal and sheds light on prostate cancer lethality.SignificanceRadiation is standard of care in prostate cancer. Yet, we have little understanding of its failure. We demonstrate a new paradigm that radioresistance is fractionation specific and identified POLQ as a radioresistance modulator.

The analysis and interpretation of coincidence events in a Compton camera requires the comparison of the expected rates of observed events from sources with various emission rates, energy spectra and spatial distributions. Radioactive source distributions are often represented by the activity distributed among numerous voxels; each voxel having uniform internal activity and spectra within a cube. In this paper a mathematical model is constructed that predicts the expected rate of coincident Compton events from the rate of emissions from a single voxel source. This detailed model incorporates (1) the finite voxel size, (2) the blurring of the “Compton cone” by the limitations of energyresolution in the detectors and (3) the uncertainty in the Compton cone-axis due to the limited spatial resolution and ‘lever-arm’ separation between the coincident interactions. The resultant rates can be used to generate the system response matrix for source reconstruction and, therefore, are directly applicable in list-mode MLEM sourcereconstruction algorithms.

Objective.In our previous work on image reconstruction for single-layer collimatorless scintigraphy, we developed the min-min weighted robust least squares (WRLS) optimization algorithm to address the challenge of reconstructing images when both the system matrix and the projection data are uncertain. Whereas the WRLS algorithm has been successful in two-dimensional (2D) reconstruction, expanding it to three-dimensional (3D) reconstruction is difficult since the WRLS optimization problem is neither smooth nor strongly-convex. To overcome these difficulties and achieve robust image reconstruction in the presence of system uncertainties and projection noise, we propose a generalized iterative method based on the maximum likelihood expectation maximization (MLEM) algorithm, hereinafter referred to as the Masked-MLEM algorithm.Approach.In the Masked-MLEM algorithm, only selected subsets ('masks') from the system matrix and the projection contribute to the image update to satisfy the constraints imposed by the system uncertainties. We validate the Masked-MLEM algorithm and compare it to the standard MLEM algorithm using experimental data obtained from both collimated and uncollimated imaging instruments, including parallel-hole collimated SPECT, 2D collimatorless scintigraphy, and 3D collimatorless tomography. Additionally, we conduct comprehensive Monte Carlo simulations for 3D collimatorless tomography to further validate the effectiveness of the Masked-MLEM algorithm in handling different levels of system uncertainties.Main results.The Masked-MLEM and standard MLEM reconstructions are similar in cases with negligible system uncertainties, whereas the Masked-MLEM algorithm outperforms the standard MLEM algorithm when the system matrix is an approximation. Importantly, the Masked-MLEM algorithm ensures reliable image reconstruction across varying levels of system uncertainties.Significance.With a good choice of system uncertainty and without requiring accurate knowledge of the actual system matrix, the Masked-MLEM algorithm yields more robust image reconstruction than the standard MLEM algorithm, effectively reducing the likelihood of erroneously reconstructing higher activities in regions without radioactive sources.

Haiti is among the most climate-vulnerable nations in the world, and Haitian youth face disproportionate risks to their health and well-being. Yet, to date, few studies have partnered with young people to position them as agents of change addressing climate change impacts in their communities, particularly in Global South contexts. As a step toward addressing this important gap, the present study used in-depth interviews (N = 6) to explore the multi-faceted behavioral developmental impacts on Haitian students (ages 20-30 years) who took part in a participatory environmental education program focused on access to clean water in Jacmel, a coastal city in Southern Haiti. The program combined hydrology and ecosystem education with youth-led water quality testing, community surveys, and data mapping--enabling students to collect, analyze, and visualize locally-meaningful data with real-world significance. Thematic analysis (TA) of post-program interviews conducted with program staff (n = 2) and students (n = 4) resulted in three major themes describing program-based developmental impacts equipping youth to address climate-driven threats in their community: (1) learning and skills development: Youth gained a deeper knowledge of hydrological and ecological systems, as well as research, digital, and technology skills; (2) health and environmental behaviors: Youth were experiencing and advocating behavioral shifts associated with preventing waterborne illnesses and protecting local ecosystems; and (3) civic engagement: Youth were developing a critical mindset regarding power relations and social change and were simultaneously motivated to disseminate local data to raise community awareness and engage with local authorities to improve environmental conditions. Findings shed light on the transformative potential of environmental and civic science education to engage young people as key actors in building adaptive capacity and reducing climate vulnerability. Implications for developmental science are discussed.

BackgroundTargeted alpha-particle therapy (TAT) has great promise as a cancer treatment. Arguably the most promising TAT radionuclide that has been proposed is 225 Ac. The development of 225 Ac-based radiopharmaceuticals has been hampered due to the lack of effective means to study the daughter redistribution of these agents in small animals at the preclinical stage.PurposeThe ability to directly image the daughters, namely 221 Fr and 213 Bi, via their gamma-ray emissions would be a boon for preclinical studies. That said, conventional medical imaging modalities, including single photon emission computed tomography (SPECT) based on nonmultiplexed collimation, cannot be employed due to sensitivity limitations.MethodsAs an alternative, we propose the use of both coded aperture and Compton imaging with the former modality suited to the 218-keV gamma-ray emission of 221 Fr and the latter suited to the 440-keV gamma-ray emission of 213 Bi.ResultsThis work includes coded aperture images of 221 Fr and Compton images of 213 Bi in tumor-bearing mice injected with 225 Ac-based radiopharmaceuticals.ConclusionsThese results are the first demonstration of visualizing and quantifying the 225 Ac daughters in small animals through the application of coded aperture and Compton imaging.

Malaz A Boustani,1–3 Amie Frame,1,2 Stephanie Munger,1,2 Patrick Healey,4 Jessie Westlund,5 Martin Farlow,6,7 Ann Hake,8 Mary Guerriero Austrom,6,9 Polly Shepard,10 Corby Bubp,10 Jose Azar,3 Arif Nazir,3 Nadia Adams,11 Noll L Campbell,1,2,12,13 Azita Chehresa,5 Paul Dexter2,31Indiana University Center for Aging Research, 2Regenstrief Institute, Inc, 3Department of Medicine, Indiana University School of Medicine (IUSM), 4St Vincent Health Network, 5Community Health Network, 6Indiana Alzheimer Disease Center, IUSM, 7Department of Neurology, IUSM, 8Eli Lilly and Company, 9Department of Psychiatry, IUSM, 10The Memory Clinic of Indianapolis, 11Indiana University Health, Indianapolis, IN, USA; 12Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, IN, USA; 13Department of Pharmacy, Wishard Health Services, Indianapolis, IN, USABackground: The US Institute of Medicine has recommended an integrated, locally sensitive collaboration among the various members of the community, health care systems, and research organizations to improve dementia care and dementia research.Methods: Using complex adaptive system theory and reflective adaptive process, we developed a professional network called the “Indianapolis Discovery Network for Dementia” (IDND). The IDND facilitates effective and sustainable interactions among a local and diverse group of dementia researchers, clinical providers, and community advocates interested in improving care for dementia patients in Indianapolis, Indiana.Results: The IDND was established in February 2006 and now includes more than 250 members from more than 30 local (central Indiana) organizations representing 20 disciplines. The network uses two types of communication to connect its members. The first is a 2-hour face-to-face bimonthly meeting open to all members. The second is a web-based resource center (http://www.indydiscoverynetwork.org). To date, the network has: (1) accomplished the development of a network website with an annual average of 12,711 hits per day; (2) produced clinical tools such as the Healthy Aging Brain Care Monitor and the Anticholinergic Cognitive Burden Scale; (3) translated and implemented the collaborative dementia care model into two local health care systems; (4) created web-based tracking software, the Enhanced Medical Record for Aging Brain Care (eMR-ABC), to support care coordination for patients with dementia; (5) received more than USD$24 million in funding for members for dementia-related research studies; and (6) adopted a new group-based problem-solving process called the “IDND consultancy round.”Conclusion: A local interdisciplinary “think-tank” network focused on dementia that promotes collaboration in research projects, educational initiatives, and quality improvement efforts that meet the local research, clinical, and community needs relevant to dementia care has been built.Keywords: cognitive impairment, community research, translational research, complex adaptive system

Patrick O Monahan,1 Malaz A Boustani,1–3,6 Catherine Alder,2,3,6 James E Galvin,7 Anthony J Perkins,2,3 Patrick Healey,4 Azita Chehresa,5 Polly Shepard,8 Corby Bubp,8 Amie Frame,2,3 Chris Callahan1–3,61Indiana University School of Medicine, 2Indiana University Center for Aging Research, 3Regenstrief Institute Inc, 4St Vincent’s Health Network, 5Community Health Network, 6Wishard Health Services, Eskenazi Health, Indianapolis IN, 7Alzheimer Disease Center, Departments of Neurology and Psychiatry, New York University School of Medicine, New York, NY, 8Memory Clinic of Indianapolis, Indianapolis, IN, USABackground: Dementia care providers need a clinical assessment tool similar to the blood pressure cuff (sphygmomanometer) used by clinicians and patients for managing hypertension. A “blood pressure cuff” for dementia would be an inexpensive, simple, user-friendly, easily standardized, sensitive to change, and widely available multidomain instrument for providers and informal caregivers to measure severity of dementia symptoms. The purpose of this study was to assess the reliability and validity of the Healthy Aging Brain Care Monitor (HABC-Monitor) for measuring and monitoring the severity of dementia symptoms through caregiver reports.Methods: The first prototype of the HABC-Monitor was developed in collaboration with the Indianapolis Discovery Network for Dementia, which includes 200 members representing 20 disciplines from 20 local organizations, and an expert panel of 22 experts in dementia care and research. The HABC-Monitor has three patient symptom domains (cognitive, functional, behavioral/psychological) and a caregiver quality of life domain. Patients (n = 171) and their informal caregivers (n = 171) were consecutively approached and consented during, or by phone shortly following, a patient’s routine visit to their memory care provider.Results: The HABC-Monitor demonstrated good internal consistency (0.73–0.92); construct validity indicated by correlations with the caregiver-reported Neuropsychiatric Inventory (NPI) total score and NPI caregiver distress score; sensitivity to three-month change compared with NPI “reliable change” groups; and known-groups validity, indicated by significant separation of Mini-Mental Status Examination severity groups and clinical diagnostic groups. Although not designed as a screening study, there was evidence for good operating characteristics, according to area under the receiver-operator curve with respect to gold standard clinical diagnoses, relative to Mini-Mental Status Examination or NPI.Conclusion: The HABC-Monitor demonstrates good reliability and validity as a clinically practical multidimensional tool for monitoring symptoms of dementia through the informal caregiver.Keywords: dementia, symptoms, monitor, validation, cognitive impairment, memory care

This paper examines the issue of student choice across subject streams in recent government reforms to China's National College Entrance Exam (NCEE). Utilizing data from a case study of an urban high school in Beijing, it argues that student choice of subjects across previous streams of science or fine arts runs counter to existing institutional structures at the secondary and higher education level, consideration of pedagogical techniques that differ by streams, and a "bias" for science grounded in sociohistorical concerns of national development.

Abstract Rapid and accurate maps of floods across large domains, with high temporal resolution capturing event peaks, have applications for flood forecasting and resilience, damage assessment, and parametric insurance. Satellite imagery produces incomplete observations spatially and temporally, and hydrodynamic models require tradeoffs between computational efficiency and accuracy. We address these challenges with a novel flood model which predicts surface water area from the U.S. National Water Model using a convolutional neural network (NWM‐CNN). We trained NWM‐CNN on 780 flood events, at a 250 m resolution with an RMSE of 4.58% on held out validation geographies. We demonstrate NWM‐CNN across California during the 2023 atmospheric rivers, comparing predictions against Sentinel‐1 mapped flood observations. We compared historical predictions from 1979 to 2023 to flood damage reports in Sacramento County, California. Results show that NWM‐CNN captures inundation extent better than the Height Above Nearest Drainage (HAND) approach (25%–36% RMSE, respectively).