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Abstract Obesity is associated with increased cancer risk, yet the underlying mechanisms remain elusive. Obesity-associated cancers involve disruptions in metabolic and cellular pathways, which can lead to genomic instability. Repetitive DNA sequences capable of adopting alternative DNA structures (e.g., H-DNA) stimulate mutations and are enriched at mutation hotspots in human cancer genomes. However, it is not known if obesity impacts DNA repeat-mediated endogenous mutation hotspots. We address this gap by measuring mutation frequencies in obese and normal-weight transgenic reporter mice carrying either a control human B-DNA- or an H-DNA-forming sequence (from a translocation hotspot in c-MYC in Burkitt lymphoma). Here, we discover that H-DNA-induced DNA damage and mutations are elevated in a tissue-specific manner, and DNA repair efficiency is reduced in obese mice compared to those on the control diet. These findings elucidate the impact of obesity on cancer-associated endogenous mutation hotspots, providing mechanistic insight into the link between obesity and cancer.

Abstract For the fields of implementation science and health equity, understanding and being responsive to local contexts is of utmost importance to better inform the development, implementation, and evaluation of healthcare and public health interventions to increase their uptake and sustainment. Contexts are multi-level and include political, historical, economic, and social factors that influence health, as well as organizational characteristics, reflecting the richness of members’ views, resources, values, and needs. Poor alignment between solutions and those contextual characteristics could have an impact on inequities. The PRISM (Practical Robust Implementation and Sustainability Model) is a context-based implementation science framework that incorporates RE-AIM outcomes (Reach, Effectiveness, Adoption, Implementation, Maintenance) and offers guidance to researchers, practitioners, and their patient and community partners on how to conceptualize, assess, and address contextual domains with a focus on health equity. Drawing from systems thinking, participatory engagement, and health equity principles, this commentary expands on previous work to 1) offer a novel perspective on how to align an intervention’s core functions and forms with the PRISM’s contextual domains, and 2) foster an ongoing and iterative engagement process with diverse partners throughout the research and practice process using a co-creation approach. We recommend intervention-to-context alignment through iterative cycles. To that end, we present the RE-AIM Framework’s ‘outcomes cascade’ to illustrate touch points of opportunity and gaps within and across each of the five RE-AIM outcomes to illustrate ‘where things go wrong’. We present a case study to illustrate and offer recommendations for research and practice efforts to increase contextual responsiveness, and enhance alignment with context before, during, and after implementation efforts and to ensure equity is being addressed. We strive to make a conceptual contribution to advance the field of pragmatic research and implementation of evidence-based practices through the application of the contextually-based PRISM framework with a focus on health equity.

Abstract Background The field of implementation science was developed to address the significant time delay between establishing an evidence-based practice and its widespread use. Although implementation science has contributed much toward bridging this gap, the evidence-to-practice chasm remains a challenge. There are some key aspects of implementation science in which advances are needed, including speed and assessing causality and mechanisms. The increasing availability of artificial intelligence applications offers opportunities to help address specific issues faced by the field of implementation science and expand its methods. Main text This paper discusses the many ways artificial intelligence can address key challenges in applying implementation science methods while also considering potential pitfalls to the use of artificial intelligence. We answer the questions of “why” the field of implementation science should consider artificial intelligence, for “what” (the purpose and methods), and the “what” (consequences and challenges). We describe specific ways artificial intelligence can address implementation science challenges related to (1) speed, (2) sustainability, (3) equity, (4) generalizability, (5) assessing context and context-outcome relationships, and (6) assessing causality and mechanisms. Examples are provided from global health systems, public health, and precision health that illustrate both potential advantages and hazards of integrating artificial intelligence applications into implementation science methods. We conclude by providing recommendations and resources for implementation researchers and practitioners to leverage artificial intelligence in their work responsibly. Conclusions Artificial intelligence holds promise to advance implementation science methods (“why”) and accelerate its goals of closing the evidence-to-practice gap (“purpose”). However, evaluation of artificial intelligence’s potential unintended consequences must be considered and proactively monitored. Given the technical nature of artificial intelligence applications as well as their potential impact on the field, transdisciplinary collaboration is needed and may suggest the need for a subset of implementation scientists cross-trained in both fields to ensure artificial intelligence is used optimally and ethically.

Abstract Background This pilot study examined the preliminary effectiveness of the PREVENT digital intervention that supports health care teams in delivering health behavior counseling on cancer survivors’ motivation to change behavior, their physical activity and food intake behaviors, and cardiovascular health (CVH). Methods Clinicians (physicians, nurse practitioners) at three urban cancer survivorship clinics were trained to use PREVENT. Patients were randomized to the PREVENT intervention or a wait-list routine care control group. Eligibility criteria for patients included: between ages 12–39, overweight or obese, were at least 6-months post-active cancer treatment, and had sufficient English proficiency. Results Fifty-five participants were enrolled; 27 were randomized to the PREVENT intervention and 28 to wait-list routine care control. The majority of the participants (82%) identified as non-Hispanic white, with an average age of 19.8 (SD ± 5.2) years. Patients that received the PREVENT intervention had greater increases in their self-efficacy, vigorous activity and number of food recommendations met than those who received routine clinical care. Changes in willingness, knowledge, and CVH outcomes were not significant. Conclusions The PREVENT digital intervention may provide improvements in preventive behaviors among AYA cancer survivors by supporting care teams with delivering evidence-based, tailored behavior change recommendations and resources to support patient health. Trial registration This trial ( NCT04623190 ) was registered on 11/02/2022.

RESUMO Este artigo analisa os papéis relativos da política salarial e das condições econômicas na determinação dos salários dos trabalhadores da produção entre 1960 e 1976 em cinco indústrias manufatureiras em São Paulo, Brasil. A análise de três subperíodos considera a direção da influência da política salarial sobre os salários reais, as mudanças observadas nos salários reais e o “desvio salarial” em relação a um índice salarial previsto com base na política salarial. Os resultados indicam que o impacto das políticas salariais repressivas durante os períodos de “apertamento salarial” de 1965-67 e 1973 variou de acordo com o tamanho da empresa e propriedade e com as condições econômicas gerais.

Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1β in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1β. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection.

Abstract Background Implementation science and health services outcomes research each focus on many constructs that are likely interrelated. Both fields would be informed by increased understanding of these relationships. However, there has been little to no investigation of the relationships between implementation outcomes and service outcomes, despite general acknowledgement that both types of outcomes are important in the pathway to individual and population health outcomes. Given the lack of objective data about the links between implementation and service outcomes, an initial step in elucidating these relationships is to assess perceptions of these relationships among researchers and practitioners in relevant fields. The purpose of this paper is to assess perceived relationships between Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework outcomes and service outcomes, testing five a priori hypotheses about which perceived relationships may be strongest. Methods A cross-sectional online survey was administered to a convenience sample of implementation scientists, health services researchers, and public health and medical practitioners from a variety of settings. Respondents provided information on their discipline, training, practice and research settings, and levels of experience in health service outcomes research, implementation science, and the RE-AIM framework. Next, they rated perceived relationships between RE-AIM and service outcomes. Repeated measures analysis of variance were used to test a priori hypotheses. Exploratory analyses assessed potential differences in mean ratings across groups of respondents categorized by discipline, setting, and levels of implementation science, health services, and RE-AIM experience. Results Surveys were completed by 259 respondents, most of whom were employed in academic and medical settings. The majority were doctoral-level researchers and educators or physicians. Reported levels of experience with implementation research, health services research, and the RE-AIM framework varied. The strongest perceived relationships overall were between Implementation/Fidelity and Effectiveness (as a service outcome); Maintenance and Efficiency; Reach and Equity; Adoption and Equity; Implementation/Adaptation and Patient-Centeredness; Adoption and Patient-Centeredness; and Implementation/Fidelity and Safety. All but one of the a priori hypotheses were supported. No significant differences in ratings of perceived relationships were observed among subgroups of respondents. Conclusions This study is an initial step in developing conceptual understanding of the links between implementation outcomes, health services outcomes, and health outcomes. Our findings on perceived relationships between RE-AIM and services outcomes suggest some areas of focus and identify several areas for future research to advance both implementation science and health services research toward common goals of improving health outcomes.

We investigated the activity of cefiderocol/β-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most “Critical Priority” group of MDR bacteria (carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol/avibactam, /sulbactam, or /tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log10 CFU/mL. We reported the high antimicrobial activity of the cefiderocol/sulbactam combination against carbapenem-resistant Enterobacterales, P. aeruginosa, and A. baumannii; of the cefiderocol/avibactam combination against carbapenem-resistant Enterobacterales; and of the cefiderocol/tazobactam combination against carbapenem-resistant Enterobacterales and P. aeruginosa. Our results demonstrate that all β-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol/tazobactam combination resulted in being active only against carbapenem-resistant Enterobacterales and P. aeruginosa, and cefiderocol/avibactam was only active against carbapenem-resistant Enterobacterales.

Qubit-specific measurement in a superconducting quantum processor requires physical interconnects that traverse 4 orders of magnitude in temperature from 293 K to 10 mK. Although the quantum processor can be thermalized and shielded from electromagnetic noise, the interconnects themselves introduce an unavoidable remote heat bath that causes decoherence of quantum states. In the present work, we report quantitative and device-independent measurements of the power radiated to the quantum processor from its control lines. Our results have been obtained using a calibrated bolometer that operates within a millikelvin environment with time-resolved measurement capability. In the limit of zero applied power, the noise power emitted to the quantum processor is equivalent to that of a blackbody with temperature 63–71 mK for the prototypical drive lines in the study. Experimentally, we increase the applied power of a simulated control signal to map out the resulting temperature rise and thermal time constant of five prototypical drive-line varieties. We input the data to an open quantum system model to demonstrate the trade-off between dissipated signal power, transmon-qubit lifetime, pure dephasing, gate fidelity, and the implied decoherence rates due to self-heating during microwave operations. Beyond explaining dephasing rates observed in the literature, our work sets the stage for accurate noise modeling in novel quantum computer interfacing methods due to our device-agnostic approach.

James Webb Space Telescope NIRCam images have revealed 154 reliable globular cluster (GC) candidates around the z = 0.0513 elliptical galaxy VV 191a after subtracting 34 likely interlopers from background galaxies inside our search area. NIRCam broadband observations are made at 0.9–4.5 μ m using the F090W, F150W, F356W, and F444W filters. Using point-spread-function-matched photometry, the data are analyzed to present color–magnitude diagrams and color distributions that suggest a relatively uniform population of GCs, except for small fractions of reddest (5%–8%) and bluest (2%–4%) outliers. GC models in the F090W versus (F090W–F150W) diagram fit the NIRCam data well and show that the majority of GCs detected have a mass of ∼10 ^6.5 M _⊙ , with metallicities [Fe/H] spanning the typical range expected for GCs (−2.5 ≲ [Fe/H]≲ 0.5). However, the models predict ∼0.3–0.4 mag bluer (F356W–F444W) colors than the NIRCam data for a reasonable range of GC ages, metallicities, and reddening. Although our data do not quite reach the luminosity function turnover, the measured luminosity function is consistent with previous measurements, suggesting an estimated peak at m _AB ∼ −9.4 ± 0.2 mag in the F090W filter.

A wealth of observations have long suggested that the vast majority of isolated classical dwarf galaxies ( M _* = 10 ^7 –10 ^9 M _⊙ ) are currently star forming. However, recent observations of the large abundance of “ultra-diffuse galaxies” beyond the reach of previous large spectroscopic surveys suggest that our understanding of the dwarf galaxy population may be incomplete. Here we report the serendipitous discovery of an isolated quiescent dwarf galaxy in the nearby Universe, which was imaged as part of the JWST PEARLS Guaranteed Time Observation program. Remarkably, individual red-giant branch stars are visible in this near-IR imaging, suggesting a distance of 30 ± 4 Mpc, and a wealth of archival photometry point to an sSFR of 2 × 10 ^−11 yr ^−1 and star formation rate of 4 × 10 ^−4 M _⊙ yr ^−1 . Spectra obtained with the Lowell Discovery Telescope find a recessional velocity consistent with the Hubble Flow and >1500 km s ^−1 separated from the nearest massive galaxy in Sloan Digital Sky Survey suggesting that this galaxy was either quenched from internal mechanisms or had a very high-velocity (≳1000 km s ^−1 ) interaction with a nearby massive galaxy in the past. This analysis highlights the possibility that many nearby quiescent dwarf galaxies are waiting to be discovered and that JWST has the potential to resolve them.

Abstract Introduction: The slow adoption of evidence-based interventions reflects gaps in effective dissemination of research evidence. Existing studies examining designing for dissemination (D4D), a process that ensures interventions and implementation strategies consider adopters’ contexts, have focused primarily on researchers, with limited perspectives of practitioners. To address these gaps, this study examined D4D practice among public health and clinical practitioners in the USA. Methods: We conducted a cross-sectional study among public health and primary care practitioners in April to June 2022 (analyzed in July 2022 to December 2022). Both groups were recruited through national-level rosters. The survey was informed by previous D4D studies and pretested using cognitive interviewing. Results: Among 577 respondents, 45% were public health and 55% primary care practitioners, with an overall survey response rate of 5.5%. The most commonly ranked sources of research evidence were email announcements for public health practitioners (43.7%) and reading academic journals for clinical practitioners (37.9%). Practitioners used research findings to promote health equity (67%) and evaluate programs/services (66%). A higher proportion of clinical compared to public health practitioners strongly agreed/agreed that within their work setting they had adequate financial resources (36% vs. 23%, p < 0.001) and adequate staffing (36% vs. 24%, p = 0.001) to implement research findings. Only 20% of all practitioners reported having a designated individual or team responsible for finding and disseminating research evidence. Conclusions: Addressing both individual and modifiable barriers, including organizational capacity to access and use research evidence, may better align the efforts of researchers with priorities and resources of practitioners.

Abstract Background To increase uptake of implementation science (IS) methods by researchers and implementers, many have called for ways to make it more accessible and intuitive. The purpose of this paper is to describe the iPRISM webtool (Iterative, Practical, Robust Implementation and Sustainability Model) and how this interactive tool operationalizes PRISM to assess and guide a program’s (a) alignment with context, (b) progress on pragmatic outcomes, (c) potential adaptations, and (d) future sustainability across the stages of the implementation lifecycle. Methods We used an iterative human-centered design process to develop the iPRISM webtool. Results We conducted user-testing with 28 potential individual and team-based users who were English and Spanish speaking from diverse settings in various stages of implementing different types of programs. Users provided input on all aspects of the webtool including its purpose, content, assessment items, visual feedback displays, navigation, and potential application. Participants generally expressed interest in using the webtool and high likelihood of recommending it to others. The iPRISM webtool guides English and Spanish-speaking users through the process of iteratively applying PRISM across the lifecycle of a program to facilitate systematic assessment and alignment with context. The webtool summarizes assessment responses in graphical and tabular displays and then guides users to develop feasible and impactful adaptations and corresponding action plans. Equity considerations are integrated throughout. Conclusions The iPRISM webtool can intuitively guide individuals and teams from diverse settings through the process of using IS methods to iteratively assess and adapt different types of programs to align with the context across the implementation lifecycle. Future research and application will continue to develop and evaluate this IS resource.

Abstract Background Haemoglobin SC (HbSC) is a common form of sickle cell disease (SCD), especially among individuals of West African ancestry. Persons with HbSC disease suffer from the same clinical complications and reduced quality of life that affect those with sickle cell anaemia (HbSS/Sβ0). Retrospective anecdotal data suggest short-term safety and benefits of hydroxyurea for treating HbSC, yet rigorous prospective data are lacking regarding optimal dosing, clinical and laboratory effects, long-term safety and benefits, and appropriate endpoints to monitor. Prospective Investigation of Variables as Outcomes for Treatment (PIVOT) was designed with three aims: (1) to measure the toxicities of hydroxyurea treatment on laboratory parameters, (2) to assess the effects of hydroxyurea treatment on sickle-related clinical and laboratory parameters, and (3) to identify study endpoints suitable for a future definitive phase III trial of hydroxyurea treatment of HbSC disease. Methods PIVOT is a randomised, placebo-controlled, double blind clinical trial of hydroxyurea. Approximately 120 children and 120 adults ages 5–50 years with HbSC disease will be enrolled, screened for 2 months, and then randomised 1:1 to once-daily oral hydroxyurea or placebo. Study treatment will be prescribed initially at 20 ± 5 mg/kg/day with an opportunity to escalate the dose twice over the first 6 months. After 12 months of blinded study treatment, all participants will be offered open-label hydroxyurea for up to 4 years. Safety outcomes include treatment-related cytopenias, whole blood viscosity, and adverse events. Efficacy outcomes include a variety of laboratory and clinical parameters over the first 12 months of randomised treatment, including changes in haemoglobin and fetal haemoglobin, intracranial arterial velocities measured by transcranial Doppler ultrasound, cerebral oxygenation using near infrared spectrometry, spleen volume and kidney size by ultrasound, proteinuria, and retinal imaging. Exploratory outcomes include functional erythrocyte analyses with ektacytometry for red blood cell deformability and point-of-sickling, patient-reported outcomes using the PROMIS questionnaire, and 6-min walk test. Discussion For children and adults with HbSC disease, PIVOT will determine the safety of hydroxyurea and identify measurable changes in laboratory and clinical parameters, suitable for future prospective testing in a definitive multi-centre phase III clinical trial. Trial registration PACTR, PACTR202108893981080. Registered 24 August 2021, https://pactr.samrc.ac.za

Abstract Background Logic models map the short-term and long-term outcomes that are expected to occur with a program, and thus are an essential tool for evaluation. Funding agencies, especially in the United States (US), have encouraged the use of logic models among their grantees. They also use logic models to clarify expectations for their own funding initiatives. It is increasingly recognized that logic models should be developed through a participatory approach which allows input from those who carry out the program being evaluated. While there are many positive examples of participatory logic modeling, funders have generally not engaged grantees in developing the logic model associated with their own initiatives. This article describes an instance where a US funder of a multi-site initiative fully engaged the funded organizations in developing the initiative logic model. The focus of the case study is Implementation Science Centers in Cancer Control (ISC3), a multi-year initiative funded by the National Cancer Institute. Methods The reflective case study was collectively constructed by representatives of the seven centers funded under ISC3. Members of the Cross-Center Evaluation (CCE) Work Group jointly articulated the process through which the logic model was developed and refined. Individual Work Group members contributed descriptions of how their respective centers reviewed and used the logic model. Cross-cutting themes and lessons emerged through CCE Work Group meetings and the writing process. Results The initial logic model for ISC3 changed in significant ways as a result of the input of the funded groups. Authentic participation in the development of the logic model led to strong buy-in among the centers, as evidenced by their utilization. The centers shifted both their evaluation design and their programmatic strategy to better accommodate the expectations reflected in the initiative logic model. Conclusions The ISC3 case study demonstrates how participatory logic modeling can be mutually beneficial to funders, grantees and evaluators of multi-site initiatives. Funded groups have important insights about what is feasible and what will be required to achieve the initiative’s stated objectives. They can also help identify the contextual factors that either inhibit or facilitate success, which can then be incorporated into both the logic model and the evaluation design. In addition, when grantees co-develop the logic model, they have a better understanding and appreciation of the funder’s expectations and thus are better positioned to meet those expectations.

Dimitrios P [...]

Abstract The Centers for Medicare and Medicaid Services require hospitals to report on quality metrics which are used to financially penalize those that perform in the lowest quartile. Surgical site infections (SSIs) are a critical component of the quality metrics that target healthcare-associated infections. However, the accuracy of such hospital profiling is highly affected by small surgical volumes which lead to a large amount of uncertainty in estimating standardized hospital-specific infection rates. Currently, hospitals with less than one expected SSI are excluded from rankings, but the effectiveness of this exclusion criterion is unknown. Tools that can quantify the classification accuracy and can determine the minimal surgical volume required for a desired level of accuracy are lacking. We investigate the effect of surgical volume on the accuracy of identifying poorly performing hospitals based on the standardized infection ratio and develop simulation-based algorithms for quantifying the classification accuracy. We apply our proposed method to data from HCA Healthcare (2014–2016) on SSIs in colon surgery patients. We estimate that for a procedure like colon surgery with an overall SSI rate of 3%, to rank hospitals in the HCA colon SSI dataset, hospitals that perform less than 200 procedures have a greater than 10% chance of being incorrectly assigned to the worst performing quartile. Minimum surgical volumes and predicted events criteria are required to make evaluating hospitals reliable, and these criteria vary by overall prevalence and between-hospital variability.

Neurons project long axons that contact other distant neurons. Neurons in the medial prefrontal cortex project into the limbic system to regulate responses to reward or threat. Diminished neural activity in prefrontal cortex is associated with loss of executive function leading to drug use, yet the specific circuitry that mediate these effects is unknown. Different regions within the medial prefrontal cortex may project to differing limbic system nuclei. Here, we exploited the cell biology of intracellular membrane trafficking, fast axonal transport, to map projections from two adjacent medial prefrontal cortical regions. We used Mn(II), a calcium analog, to trace medial prefrontal cortical projections in the living animal by magnetic resonance imaging (MRI). Mn(II), a contrast agent for MRI, enters neurons through voltage-activated calcium channels and relies on kinesin-1 and amyloid-precursor protein to transport out axons to distal destinations. Aqueous MnCl2 together with fluorescent dextran (3–-5 nL) was stereotactically injected precisely into two adjacent regions of the medial prefrontal cortex: anterior cingulate area (ACA) or infralimbic/prelimbic (IL/PL) region. Projections were traced, first live by manganese-enhanced MRI (MEMRI) at four time points in 3D, and then after fixation by microscopy. Data-driven unbiased voxel-wise statistical maps of aligned normalized MR images after either ACA or IL/PL injections revealed statistically significant progression of Mn(II) over time into deeper brain regions: dorsal striatum, globus pallidus, amygdala, hypothalamus, substantia nigra, dorsal raphe and locus coeruleus. Quantitative comparisons of these distal accumulations at 24 h revealed dramatic differences between ACA and IL/PL injection groups throughout the limbic system, and most particularly in subdomains of the hypothalamus. ACA projections targeted dorsomedial nucleus of the hypothalamus, posterior part of the periventricular region and mammillary body nuclei as well as periaqueductal gray, while IL/PL projections accumulated in anterior hypothalamic areas and lateral hypothalamic nuclei as well as amygdala. As hypothalamic subsegments relay CNS activity to the body, our results suggest new concepts about mind-body relationships and specific roles of distinct yet adjacent medial prefrontal cortical segments. Our MR imaging strategy, when applied to follow other cell biological processes in the living organism, will undoubtedly lead to an expanded perspective on how minute details of cellular processes influence whole body health and wellbeing.

RT-qPCR remains a key diagnostic methodology for COVID-19/SARS-CoV-2. Typically, nasal or saliva swabs from patients are placed in virus transport media (VTM), RNA is extracted at the pathology laboratory, and viral RNA is measured using RT-qPCR. In this study, we describe the use of TNA-Cifer Reagent E in a pre-clinical evaluation study to inactivate SARS-CoV-2 as well as prepare samples for RT-qPCR. Adding 1 part TNA-Cifer Reagent E to 5 parts medium containing SARS-CoV-2 for 10 min at room temperature inactivated the virus and permitted RT-qPCR detection. TNA-Cifer Reagent E was compared with established column-based RNA extraction and purification methodology using a panel of human clinical nasal swab samples (n = 61), with TNA-Cifer Reagent E showing high specificity (100%) and sensitivity (97.37%). Mixtures of SARS-CoV-2 virus and TNA-Cifer Reagent E could be stored for 3 days at room temperature or for 2 weeks at 4°C without the loss of RT-qPCR detection sensitivity. The detection sensitivity was preserved when TNA-Cifer Reagent E was used in conjunction with a range of VTM for saliva samples but only PBS (Gibco) and Amies Orange for nasal samples. Thus, TNA-Cifer Reagent E improves safety by rapidly inactivating the virus during sample processing, potentially providing a safe means for molecular SARS-CoV-2 testing outside traditional laboratory settings. The reagent also eliminates the need for column-based and/or automated viral RNA extraction/purification processes, thereby providing cost savings for equipment and reagents, as well as reducing processing and handling times.

Abstract Background The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group provides the first new clinical practice recommendations from the National Heart, Lung, and Blood Institute (NHLBI) since the previous 2007 asthma management guidelines. Guideline implementability was a high priority for the expert panel, and many approaches were undertaken to enhance the implementability of this clinical guideline update. Within the report, specific implementation guidance sections provide expanded summaries for each recommendation to quickly assist users. The implementation guidance incorporates findings from NHLBI-sponsored focus groups conducted with people who have asthma, caregivers, and health care providers. The findings were used to identify the types of information and tools that individuals with asthma, their caregivers, and their health care providers would find most helpful; ensure that the new asthma guidelines reflect the voices of individuals with asthma and their caregivers; and identify potential barriers to uptake by individuals with asthma and their caregivers. The expert panel used a GRADE-based approach to develop evidence-to-decision tables that provided a framework for assessing the evidence and consideration of a range of contextual factors that influenced the recommendations such as desirable and undesirable effects, certainty of evidence, values, balance of effects, acceptability, feasibility, and equity. To facilitate uptake in clinical care workflow, selected recommendations were converted into structured, computer-based clinical decision support artifacts, and the new recommendations were integrated into existing treatment tables used in the 2007 asthma management guidelines, with which many users are familiar. A comprehensive approach to improve guidelines dissemination and implementation included scientific publications, patient materials, media activities, stakeholder engagement, and professional education. Conclusion We developed evidence-based clinical practice guideline updates for asthma management focused on six topic areas. The guideline development processes and implementation and dissemination activities undertaken sought to enhance implementability by focusing on intrinsic factors as described by Kastner, Gagliardi, and others to produce usable, adoptable, and adaptable guidelines. Enhanced collaboration during guideline development between authors, informaticists, and implementation scientists may facilitate the development of tools that support the application of recommendations to further improve implementability.

Objectives: Medical care in low-income countries is often limited by inadequate resources, treatment facilities, and the necessary infrastructure for healthcare delivery. We hypothesized that the development of an independently functioning, internationally supported Kenyan cardiac surgical training program could address these issues through targeted investment. Methods: A review was conducted of the programmatic structure and clinical outcomes from January 2008 to October 2021 at Tenwek Hospital, Bomet, Kenya. Program development phases included (1) cardiovascular care provided by 1 full-time US board-certified cardiothoracic surgeon; (2) short-term volunteer surgical teams from the United States and Canada; and (3) development of a cardiothoracic residency program based on the Society of Thoracic Surgeons training curriculum. Patient demographics and outcomes were analyzed throughout each phase of program development. Results: A total of 817 cardiac procedures were performed during the study period, including 236 congenital (28.8%) and 581 adult (71.1%) procedures. Endemic rheumatic valvular heart disease predominated (581 patients, 62.3%). Local surgical team case volume grew over the study period, overtaking visiting team volume in 2019. Perioperative mortality was 2.1% and consistent between the visiting teams and the locally trained teams. Surgical training via a 3-year cardiothoracic residency is now in its fourth year, with the 2 graduates now retained as full-time teaching staff. Conclusions: Global health partnerships have the potential to address unmet needs in cardiac care within low- and middle-income countries. These data support the concept that acceptable clinical outcomes and consistent growth in volume can be achieved during the transition toward fully independent cardiac surgical care.

Metal–organic frameworks have demonstrated promise for the storage and release of biologically active gases. Here, an in situ single crystal X-ray diffraction study using synchrotron radiation elucidates the binding mechanisms and geometries of nitric oxide and carbon monoxide gases in activated frameworks Ni-CPO-27 and Co-4,6-dihydroxyisophthalate.

Abstract Background Despite lung cancer being a leading cause of death in the United States and lung cancer screening (LCS) being a recommended service, many patients eligible for screening do not receive it. Research is needed to understand the challenges with implementing LCS in different settings. This study investigated multiple practice members and patient perspectives impacting rural primary care practices related to LCS uptake by eligible patients. Methods This qualitative study involved primary care practice members in multiple roles (clinicians n = 9, clinical staff n = 12 and administrators n = 5) and their patients (n = 19) from 9 practices including federally qualified and rural health centers (n = 3), health system owned (n = 4) and private practices (n = 2). Interviews were conducted regarding the importance of and ability to complete the steps that may result in a patient receiving LCS. Data were analyzed using a thematic analysis with immersion crystallization then organized using the RE-AIM implementation science framework to illuminate and organize implementation issues. Results Although all groups endorsed the importance of LCS, all also struggled with implementation challenges. Since assessing smoking history is part of the process to identify eligibility for LCS, we asked about these processes. We found that smoking assessment and assistance (including referral to services) were routine in the practices, but other steps in the LCS portion of determining eligibility and offering LCS were not. Lack of knowledge about screening and coverage, patient stigma, and resistance and practical considerations such as distance to LCS testing facilities complicated completion of LCS compared to screening for other types of cancer. Conclusions Limited uptake of LCS results from a range of multiple interacting factors that cumulatively affect consistency and quality of implementation at the practice level. Future research should consider team-based approaches to conduct of LCS eligibility and shared decision making.

Abstract Background Hawksbill turtles (Eretmochelys imbricata) are Critically Endangered throughout their global range, and concerningly little is known about this species in the Red Sea. With large-scale coastal development projects underway in the northern Red Sea, it is critical to understand the movement and habitat use patterns of hawksbill turtles in this environmentally unique region, so that effective conservation strategies can be implemented. We satellite tagged three hawksbill turtles, one 63 cm curved carapace length adult male captured near Wahlei Island, one 55 cm turtle captured in the Gulf of Aqaba, and one 56 cm turtle suffering from a floating syndrome which was captured at Waqqadi Island, rehabilitated, and released at Waqqadi Island. Turtles were tracked for 156, 199, and 372 days between October 2020 and November 2021. Results We calculated the home ranges and core use areas of hawksbill turtles using kernel-density estimations and found that each turtle showed high fidelity to their foraging sites. Home ranges calculated with GPS-derived locations ranged between 13.6 and 2.86 km2, whereas home ranges calculated with Argos-derived locations ranged from 38.98 to 286.45 km2. GPS-derived locations also revealed a higher proportion of time spent in coral and rock habitats compared to Argos, based on location overlap with the Allen Coral Reef Atlas. We also found that turtles were making shallow dives, usually remaining between 0 and 5 m. Conclusions While the number of tracked turtles in this study was small, it represents an important contribution to the current understanding of spatial ecology among foraging hawksbill turtles globally, and provides the first-ever reported hawksbill turtle tracking data from the Red Sea. Our results suggest that protecting coral reef habitats and implementing boating speed limits near reefs could be effective conservation measures for foraging hawksbill turtles in the face of rapid coastal development.

We present a new parametric lens model for the G165.7+67.0 galaxy cluster, which was discovered with Planck through its bright submillimeter flux, originating from a pair of extraordinary dusty star-forming galaxies (DSFGs) at z ≈ 2.2. Using JWST and interferometric mm/radio observations, we characterize the intrinsic physical properties of the DSFGs, which are separated by only ∼1″ (8 kpc) and a velocity difference Δ V ≲ 600 km s ^−1 in the source plane, and thus are likely undergoing a major merger. Boasting intrinsic star formation rates SFR _IR = 320 ± 70 and 400 ± 80 M _⊙ yr ^−1 , stellar masses of $\mathrm{log}[{M}_{\star }/{M}_{\odot }]=10.2\pm 0.1$ and 10.3 ± 0.1, and dust attenuations of A _V = 1.5 ± 0.3 and 1.2 ± 0.3, they are remarkably similar objects. We perform spatially resolved pixel-by-pixel spectral energy distribution (SED) fitting using rest-frame near-UV to near-IR imaging from JWST/NIRCam for both galaxies, resolving some stellar structures down to 100 pc scales. Based on their resolved specific star formation rates (SFRs) and UVJ colors, both DSFGs are experiencing significant galaxy-scale star formation events. If they are indeed interacting gravitationally, this strong starburst could be the hallmark of gas that has been disrupted by an initial close passage. In contrast, the host galaxy of SN H0pe has a much lower SFR than the DSFGs, and we present evidence for the onset of inside-out quenching and large column densities of dust even in regions of low specific SFR. Based on the intrinsic SFRs of the DSFGs inferred from UV through far-infrared SED modeling, this pair of objects alone is predicted to yield an observable 1.1 ± 0.2 core-collapse supernovae per year, making this cluster field ripe for continued monitoring.

We present an analysis of the ultraviolet luminosity function (UV LF) and star formation rate density of distant galaxies (7.5 < z < 13.5) in the “blank” fields of the Prime Extragalactic Areas for Reionization and Lensing Science (PEARLS) survey combined with Early Release Science data from the CEERS, GLASS, and NGDEEP surveys/fields and the first data release of JADES. We use strict quality cuts on EAZY photometric redshifts to obtain a reliable selection and characterization of high-redshift ( z > 6.5) galaxies from a consistently processed set of deep, near-infrared imaging. Within an area of 180 arcmin ^2 , we identify 1046 candidate galaxies at redshifts z > 6.5 and we use this sample to study the UV LF in four redshift bins between 7.5 < z < 13.5. The measured number density of galaxies at z = 8 and z = 9 matches those of past observations undertaken by the Hubble Space Telescope (HST). Our z = 10.5 measurements lie between early James Webb Space Telescope (JWST) results and past HST results, indicating cosmic variance may be the cause of previous high density measurements. However, the number densities of UV-luminous galaxies at z = 12.5 are high compared to predictions from simulations. When examining the star formation rate density of galaxies at this period, our observations are still largely consistent with a constant star formation efficiency, are slightly lower than previous early estimations using JWST, and support galaxy driven reionization at z ≤ 8.

A Type Ia supernova (SN) at z = 1.78 was discovered in James Webb Space Telescope Near Infrared Camera imaging of the galaxy cluster PLCK G165.7+67.0 (G165; z = 0.35). The SN is situated 1.5–2 kpc from the host-galaxy nucleus and appears in three different locations as a result of gravitational lensing by G165. These data can yield a value for Hubble’s constant using time delays from this multiply imaged SN Ia that we call “SN H0pe.” Over the cluster, we identified 21 image multiplicities, confirmed five of them using the Near-Infrared Spectrograph, and constructed a new lens model that gives a total mass within 600 kpc of (2.6 ± 0.3) × 10 ^14 M _⊙ . The photometry uncovered a galaxy overdensity coincident with the SN host galaxy. NIRSpec confirmed six member galaxies, four of which surround the SN host galaxy with relative velocity ≲900 km s ^−1 and projected physical extent ≲33 kpc. This compact galaxy group is dominated by the SN host galaxy, which has a stellar mass of (5.0 ± 0.1) × 10 ^11 M _⊙ . The group members have specific star formation rates of 2–260 Gyr ^−1 derived from the H α -line fluxes corrected for stellar absorption, dust extinction, and slit losses. Another group centered on a strongly lensed dusty star-forming galaxy is at z = 2.24. The total (unobscured and obscured) SFR of this second galaxy group is estimated to be (≳ 100 M _⊙ yr ^−1 ), which translates to a supernova rate of ∼1 SNe yr ^−1 , suggesting that regular monitoring of this cluster may yield additional SNe.

Summary: Genetic mutations that cause adult-onset neurodegenerative diseases are often expressed during embryonic stages, but it is unclear whether they alter neurodevelopment and how this might influence disease onset. Here, we show that the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), a repeat expansion in C9ORF72, restricts neural stem cell proliferation and reduces cortical and thalamic size in utero. Surprisingly, a repeat expansion-derived dipeptide repeat protein (DPR) not known to reduce neuronal viability plays a key role in impairing neurodevelopment. Pharmacologically mimicking the effects of the repeat expansion on neurodevelopment increases susceptibility of C9ORF72 mice to motor defects. Thus, the C9ORF72 repeat expansion stunts development of the brain regions prominently affected in C9ORF72 FTD/ALS patients.

ABSTRACT: Panting score (PS) is a common research tool used to assess the physiological state of cows exposed to heat stress, but it is subjective. Infrared temperature (IRT), measured by either infrared thermometers or cameras, may be a more objective and reliable alternative. Very few studies thus far have evaluated the associations between PS, IRT, and milk production. We investigated the applicability of IRT compared with PS as a means of assessing heat stress and milk yield reduction in dairy cows in tropical smallholder dairy farms (SDF). In autumn 2017, SDF located across 4 typical dairy regions of Vietnam were each visited once to collect farm (n = 32) and individual cow data (n = 344). For each SDF, heat load index (HLI) inside the cowsheds, an indicator of environmental heat load calculated from ambient temperature, humidity, and wind speed, was measured. For each cow, PS (0 indicates a cow breathing normally, not panting; 4.5 indicates an extremely heat-stressed cow with excessive panting, tongue fully extended, and excessive drooling), IRT of the cow's body, single-day energy-corrected milk yield (ECM), body weight, and body condition score were measured. Cow genotype, age, lactation number, and days in milk were recorded. The IRT of the cows' inner vulval lip (IVuT) were measured with an infrared thermometer; and the IRT of the cows' vulval surface (OVuT), inner tail base surface (ITBT), ocular area, muzzle, armpit area, paralumbar fossa area, fore udder, rear udder, fore hoof, and hind hoof were also measured with an infrared camera. Multivariate mixed-effects models were used to assess the associations between HLI with PS and IRT, and associations between PS and IRT with ECM while accounting for the effects of other cow variables. All IRT correlated positively with PS (Pearson correlation, r = 0.23–0.50). Each unit increase in HLI was associated with increases of 0.07 units in PS and 0.09 to 0.23°C in IRT. Each degree (°C) increase in IVuT, OVuT, and ITBT was associated with decreases of 0.75, 0.87, and 0.70 kg/cow per day in ECM, respectively, whereas PS and other IRT were not significantly associated with ECM. Thus, all IRT showed potential to assess the heat stress level of cows; and IVuT, OVuT, and ITBT, but not PS and other IRT, showed potential to predict ECM reduction in cows during heat stress. First cross (F1) Holstein Brown Swiss and F1 Holstein Jersey showed lower PS and yielded higher ECM than the third backcross (B3) Holstein Zebu (7/8 Holstein + 1/8 Zebu) and pure Holstein. Thus, F1 Holstein Brown Swiss and F1 Holstein Jersey could be more suitable for tropical SDF than B3 Holstein Zebu and pure Holstein.

Abstract Background The Practical, Robust Implementation and Sustainability Model (PRISM) was developed in 2008 as a contextually expanded version of the broadly used Reach, Adoption, Effectiveness, Implementation, and Maintenance (RE-AIM) framework. PRISM provides researchers a pragmatic and intuitive model to improve translation of research interventions into clinical and community practice. Since 2008, the use of PRISM increased across diverse topics, populations, and settings. This citation analysis and scoping systematic review aimed to assess the use of the PRISM framework and to make recommendations for future research. Methods A literature search was conducted using three databases (PubMed, Web of Science, Scopus) for the period of 2008 and September 2020. After exclusion, reverse citation searches and invitations to experts in the field were used to identify and obtain recommendations for additional articles not identified in the original search. Studies that integrated PRISM into their study design were selected for full abstraction. Unique research studies were abstracted for information on study characteristics (e.g., setting/population, design), PRISM contextual domains, and RE-AIM outcomes. Results A total of 180 articles were identified to include PRISM to some degree. Thirty-two articles representing 23 unique studies integrated PRISM within their study design. Study characteristics varied widely and included studies conducted in diverse contexts, but predominately in high-income countries and in clinical out-patient settings. With regards to use, 19 used PRISM for evaluation, 10 for planning/development, 10 for implementation, four for sustainment, and one for dissemination. There was substantial variation across studies in how and to what degree PRISM contextual domains and RE-AIM outcomes were operationalized and connected. Only two studies directly connected individual PRISM context domains with RE-AIM outcomes, and another four included RE-AIM outcomes without direct connection to PRISM domains. Conclusions This is the first systematic review of the use of PRISM in various contexts. While there were low levels of ‘integrated’ use of PRISM and few reports on linkage to RE-AIM outcomes, most studies included important context domains of implementation and sustainability infrastructure and external environment. Recommendations are provided for more consistent and comprehensive use of and reporting on PRISM to inform both research and practice on contextual factors in implementation.

Abstract Introduction It is not realistic for most clinicians to perform the multitude of recommended preventive primary care services. This is especially true in low resource and rural settings, creating challenges to delivering high-quality care. This study collected stakeholder input from clinicians on which services they most need to improve. Methods The authors conducted a survey of primary care physicians 9–12/2021, with an emphasis on rural practices, to assess areas in which clinicians felt the greatest needs for improvement. The survey focused on primary prevention (behavior change counseling) and cancer screening, and contrasted needs for improvement for these services vs. other types of screening, and between clinicians in rural vs. non-rural practices. Results There were 326 respondents from 4 different practice-based research networks, a wide range of practice types, 49 states and included 177 clinicians in rural settings. Respondents rated the need to improve delivery of primary prevention counseling services highest, with needs for nutrition and dietary assessment and counseling rated highest followed by physical activity and with almost no differences between rural and nonrural. Needs for improvement in cancer screenings were rated higher than non-cancer screenings, except for blood pressure screening. Conclusions Both rural and nonrural primary care clinicians feel a need for improvement, especially with primary prevention activities. Although future research is needed to replicate these findings with different populations and other types of preventive service activities, greater priority should be given to development of practical, stakeholder informed assistance and resources for primary care to conduct primary prevention.

Abstract Background Lung ultrasound (LUS) is a clinician-performed evidence-based imaging modality that has multiple advantages in the evaluation of dyspnea caused by multiple disease processes, including COVID-19. Despite these advantages, few hospitalists have been trained to perform LUS. The aim of this study was to increase adoption and implementation of LUS during the 2020 COVID-19 pandemic by using recurrent assessments of RE-AIM outcomes to iteratively revise our implementation strategies. Methods In an academic hospital, we implemented guidelines for the use of LUS in patients with COVID-19 in July 2020. Using a novel “RE-AIM dashboard,” we used an iterative process of evaluating the high-priority outcomes of Reach, Adoption, and Implementation at twice monthly intervals to inform revisions of our implementation strategies for LUS delivery (i.e., Iterative RE-AIM process). Using a convergent mixed methods design, we integrated quantitative RE-AIM outcomes with qualitative hospitalist interview data to understand the dynamic determinants of LUS Reach, Adoption, and Implementation. Results Over the 1-year study period, 453 LUSs were performed in 298 of 12,567 eligible inpatients with COVID-19 (Reach = 2%). These 453 LUS were ordered by 43 out of 86 eligible hospitalists (LUS order adoption = 50%). However, the LUSs were performed/supervised by only 8 of these 86 hospitalists, 4 of whom were required to complete LUS credentialing as members of the hospitalist procedure service (proceduralist adoption 75% vs 1.2% non-procedural hospitalists adoption). Qualitative and quantitative data obtained to evaluate this Iterative RE-AIM process led to the deployment of six sequential implementation strategies and 3 key findings including (1) there were COVID-19-specific barriers to LUS adoption, (2) hospitalists were more willing to learn to make clinical decisions using LUS images than obtain the images themselves, and (3) mandating the credentialing of a strategically selected sub-group may be a successful strategy for improving Reach. Conclusions Mandating use of a strategically selected subset of clinicians may be an effective strategy for improving Reach of LUS. Additionally, use of Iterative RE-AIM allowed for timely adjustments to implementation strategies, facilitating higher levels of LUS Adoption and Reach. Future studies should explore the replicability of these preliminary findings.

Macrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear. We found that Gal-9 binds directly to Mycobacterium tuberculosis (Mtb) and Salmonella enterica serovar Typhimurium (Stm) and localizes to Mtb in macrophages. To determine the combined contribution of membrane damage-sensing galectins to immunity, we generated Gal-3, -8, and -9 triple knockout (TKO) mice. Mtb infection of primary macrophages from TKO mice resulted in defective autophagic flux but normal bacterial replication. Surprisingly, these mice had no discernable defect in resistance to acute infection with Mtb, Stm or Listeria monocytogenes, and had only modest impairments in bacterial growth restriction and CD4 T cell activation during chronic Mtb infection. Collectively, these findings indicate that while Gal-3, -8, and -9 respond to an array of intracellular pathogens, together these membrane damage-sensing galectins play a limited role in host resistance to bacterial infection.

Hosts have evolved diverse strategies to respond to microbial infections, including the detection of pathogen-encoded proteases by inflammasome-forming sensors such as NLRP1 and CARD8. Here, we find that the 3CL protease (3CLpro) encoded by diverse coronaviruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), cleaves a rapidly evolving region of human CARD8 and activates a robust inflammasome response. CARD8 is required for cell death and the release of pro-inflammatory cytokines during SARS-CoV-2 infection. We further find that natural variation alters CARD8 sensing of 3CLpro, including 3CLpro-mediated antagonism rather than activation of megabat CARD8. Likewise, we find that a single nucleotide polymorphism (SNP) in humans reduces CARD8's ability to sense coronavirus 3CLpros and, instead, enables sensing of 3C proteases (3Cpro) from select picornaviruses. Our findings demonstrate that CARD8 is a broad sensor of viral protease activities and suggests that CARD8 diversity contributes to inter- and intraspecies variation in inflammasome-mediated viral sensing and immunopathology.

Introduction: Hydroxyurea is effective disease-modifying treatment for sickle cell anemia (SCA). Escalation to maximum tolerated dose (MTD) achieves superior benefits without additional toxicities, but requires dose adjustments with serial monitoring. Pharmacokinetic (PK)-guided dosing can predict a personalized optimal dose, which approximates MTD and requires fewer clinical visits, laboratory assessments, and dose adjustments. However, PK-guided dosing requires complex analytical techniques unavailable in low-resource settings. Simplified hydroxyurea PK analysis could optimize dosing and increase access to treatment.Methods: Concentrated stock solutions of reagents for chemical detection of serum hydroxyurea using HPLC were prepared and stored at −80C. On the day of analysis, hydroxyurea was serially diluted in human serum, then spiked with N-methylurea as an internal standard and analyzed using two commercial HPLC machines: 1) standard benchtop Agilent with 449 nm detector and 5 micron C18 column; and 2) portable PolyLC with 415 nm detector and 3.5 micron C18 column. After validation in the United States, the portable HPLC and chemicals were transported to Tanzania.Results: A calibration curve using hydroxyurea 2-fold dilutions ranging from 0 to 1000 µM was plotted against the hydroxyurea:N-methylurea ratio. In the United States, both HPLC systems yielded calibration curves with R2 > 0.99. Hydroxyurea prepared at known concentrations confirmed accuracy and precision within 10%–20% of the actual values. Both HPLC systems measured hydroxyurea with 0.99.Conclusion: Increasing access to hydroxyurea for people with SCA requires an approach that eases financial and logistical barriers while optimizing safety and benefits, especially in low-resource settings. We successfully modified a portable HPLC instrument to quantify hydroxyurea, validated its precision and accuracy, and confirmed capacity building and knowledge transfer to Tanzania. HPLC measurement of serum hydroxyurea is now feasible in low-resource settings using available laboratory infrastructure. PK-guided dosing of hydroxyurea will be tested prospectively to achieve optimal treatment responses.

During the COVID-19 pandemic, the rapid scaling of telehealth limited the extent to which proactive planning for equitable implementation was possible. The deployment of telehealth will persist in the postpandemic era, given patient preferences, advances in technologies, growing acceptance of telehealth, and the potential to overcome barriers to serve populations with limited access to high-quality in-person care. However, aspects and unintended consequences of telehealth may leave some groups underserved or unserved, and corrective implementation plans that address equitable access will be needed. The purposes of this paper are to (1) describe equitable implementation in telehealth and (2) integrate an equity lens into actionable equitable implementation.

Orthognathic surgery has evolved significantly over the past century. Osteotomies of the midface and mandible are contemporaneously used to perform independent or coordinated movements to address functional and aesthetic problems. Specific advances in the past twenty years include increasing fidelity with computer-assisted planning, the use of patient-specific fixation, expanding indications for management of upper airway obstruction, and shifts in orthodontic-surgical paradigms. This review article serves to highlight the contemporary practice of orthognathic surgery.