Dominant Condition Research Articles

Optimization of Structure‐Guided Development of Chemical Probes for the Pseudoknot RNA of the Frameshift Element in SARS‐CoV‐2

AbstractTargeting the RNA genome of SARS‐CoV‐2 is a viable option for antiviral drug development. We explored three ligand binding sites of the core pseudoknot RNA of the SARS‐CoV‐2 frameshift element. We iteratively optimized ligands, based on improved affinities, targeting these binding sites and report on structural and dynamic properties of the three identified binding sites. Available experimental 3D structures of the pseudoknot element were compared to SAXS and NMR data to validate its dominant folding state in solution. In order to experimentally map in silico predicted binding sites, NMR assignments of the majority of nucleobases were achieved by segmental labeling of the pseudoknot RNA and isotope‐filtered NMR experiments at 1.2 GHz, demonstrating the value of NMR spectroscopy to supplement modelling and docking data. Optimized ligands with enhanced affinity were shown to specifically inhibit frameshifting without affecting 0‐frame translation in cell‐free translation assays, establishing the frameshift element as target for drug‐like ligands of low molecular weight.

Tsallis holographic dark energy model in an anisotropic universe with linearly varying deceleration parameter and its correspondence with phantom

In this paper, we investigate a spatially homogeneous and anisotropic Bianchi type-I universe filled with cold dark matter and Tsallis holographic dark energy within the framework of General Relativity. We assume the cold dark matter and the Tsallis holographic dark energy to be non-interacting and obtain exact solutions of the Einstein field equations by considering a linearly varying deceleration parameter. The physical and kinematical properties of the resulting model are explored through different parameters of cosmological importance such as the Hubble parameter, the anisotropy parameter, the equation of state parameter, the jerk parameter, the snap parameter, the lerk parameter etc. The validation or violation of the four energy conditions are also checked. We find that the Weak and Dominant Energy Conditions are fulfilled but the Null and Strong Energy Conditions are violated at late time which supports the accelerated expansion of the universe. In addition, we establish the correspondence between phantom scalar field model and Tsallis holographic dark energy model.

Optimization of Structure-Guided Development of Chemical Probes for the Pseudoknot RNA of the Frameshift Element in SARS-CoV-2.

Targeting the RNA genome of SARS-CoV-2 is a viable option for antiviral drug development. We explored three ligand binding sites of the core pseudoknot RNA of the SARS-CoV-2 frameshift element. We iteratively optimized ligands, based on improved affinities, targeting these binding sites and report on structural and dynamic properties of the three identified binding sites. Available experimental 3D structures of the pseudoknot element were compared to SAXS and NMR data to validate its dominant folding state in solution. In order to experimentally map in silico predicted binding sites, NMR assignments of the majority of nucleobases were achieved by segmental labeling of the pseudoknot RNA and isotope-filtered NMR experiments at 1.2 GHz, demonstrating the value of NMR spectroscopy to supplement modelling and docking data. Optimized ligands with enhanced affinity were shown to specifically inhibit frameshifting without affecting 0-frame translation in cell-free translation assays, establishing the frameshift element as target for drug-like ligands of low molecular weight.

Population-based, first-tier genomic newborn screening in the maternity ward.

The rapid development of therapies for severe and rare genetic conditions underlines the need to incorporate first-tier genetic testing into newborn screening (NBS) programs. A workflow was developed to screen newborns for 165 treatable pediatric disorders by deep sequencing of regions of interest in 405 genes. The prospective observational BabyDetect pilot project was launched in September 2022 in a maternity ward of a public hospital in the Liege area, Belgium. In this ongoing observational study, 4,260 families have been informed of the project, and 3,847 consented to participate. To date, 71 disease cases have been identified, 30 of which were not detected by conventional NBS. Glucose-6-phosphate dehydrogenase deficiency was the most frequent disorder detected, with 44 positive individuals. Of the remaining 27 cases, 17 were recessive disorders. We also identified one false-positive case in a newborn in whom two variants in the AGXT gene were identified, which were subsequently shown to be located on the maternal allele. Nine heterozygous variants were identified in genes associated with dominant conditions. Results from the BabyDetect project demonstrate the importance of integrating biochemical and genomic methods in NBS programs. Challenges must be addressed in variant interpretation within a presymptomatic population and in result reporting and diagnostic confirmation.

Advances in Prenatal Cell-Free DNA Screening for Dominant Monogenic Conditions: A Review of Current Progress and Future Directions in Clinical Implementation.

Prenatal cell-free DNA (cfDNA) screening has advanced significantly, extending beyond detecting aneuploidies to sub-chromosomal copy number variations. However, its application for screening dominant single-gene conditions, often caused by de novo variants, remains underutilized in the general obstetric population. This study reviews recent data and experience on prenatal cfDNA screening for dominant monogenic conditions using multiple-gene panels, highlighting its potential to enhance early detection and management of genetic disorders. Integrating comprehensive cfDNA screening into routine prenatal care could complement current imaging techniques and standard prenatal cfDNA screening, which may overlook pre-symptomatic fetuses with dominant monogenic conditions in early gestation. Despite promising initial results, further research is needed to confirm the clinical validity and utility of cfDNA screening for these conditions. Larger and more diverse studies are necessary to assess the broader applicability of this technology. In addition, key challenges such as access, genetic counseling, ethical considerations, and policy development need to be addressed. A comprehensive approach, including rigorous test design, informed consent, and robust counseling, is essential for the successful adoption of expanded cfDNA screening, ultimately improving clinical outcomes.

Aspects of the geometry and topology of expanding horizons

The aim of this paper is to extend some basic results about marginally outer trapped surfaces to the context of surfaces having general null expansion. Motivated in part by recent work of Chai-Wan, we introduce the notion of g \mathfrak {g} -stability for a general closed hypersurface Σ \Sigma in an ambient initial data set and prove that, under natural energy conditions, Σ \Sigma has positive Yamabe type, that is, Σ \Sigma admits a metric of positive scalar curvature, provided Σ \Sigma is g \mathfrak {g} -stable. A similar result is obtained when Σ \Sigma is embedded in a null hypersurface of a spacetime satisfying the dominant energy condition. Area bounds under similar conditions are obtained in the case where Σ \Sigma is 2 2 -dimensional. Conditions implying g \mathfrak {g} -stability are also discussed. Finally, we obtain a spacetime positive mass theorem for initial data sets with compact boundary Σ \Sigma of positive null expansion, assuming that the dominant energy condition is sufficiently strict near Σ \Sigma . This extends recent results of Galloway-Lee and Lee-Lesourd-Unger.

Dermatoses in Ivorian Rural Areas: A Case Study of the Health District of Zouan Hounien

<i>Objective:</i> To improve the management of skin diseases in rural areas of the Zouan-Hounien health district. <i>Materials and Methods:</i> This was a prospective, cross-sectional, descriptive study conducted over five (5) days, from December 13, 2023, to December 17, 2023, in villages within the Zouan-Hounien health district. <i>Results</i>: The study included 558 patients. The age group of 0-5 years was the most represented (16%). There were more women (54%) than men. Majority were farmers (31.4%) and single (52%). Infectious dermatoses were the most common (80.1%), with fungal infections being predominant (42.5%). Scabies was the only parasitic condition (100%), frequently affecting farmers (31.1%) and children aged 0-5 years (47.6%). Among bacterial dermatoses, boils were the most prevalent (66.7%). Molluscum contagiosum was the dominant viral dermatological condition (75%). Urticaria was the leading immuno-inflammatory dermatosis (59.5%), often observed among farmers (16.4%) and the 56-85 age group (24.6%). Lipoma was the only reported tumor-related dermatosis (1 case). There were only six (6) cases of sexually transmitted infections (1.1%). Other dermatoses were primarily sweat rash (44%). <i>Conclusion</i>: Skin diseases in rural areas of the Zouan-Hounien were predominantly infections. In light of these findings, it is necessary to strengthen the capacity of paramedical personnel to improve the management of skin diseases in rural settings. In the absence of a specialist in every village, implementing tele dermatology should be considered to bridge this gap.

STUDI KASUS: OSTEOCHONDROMA SCAPULA DAN TIBIA FIBULA PADA REMAJA USIA 14 TAHUN

Multiple Hereditary Exostoses (MHE) is an autosomal dominant inherited genetic condition characterized by multiple exostoses (or osteochondromas). Genetic analysis had identified a certain type of mutated Exostosin genes, can potentially cause exostoses. A 14 years old boy referred to our hospital with a chronic hard palpable lump on his left back and right lower limb in the past 10 years, and was gradually increased in size. Laboratory test which consists of complete blood count, urinalysis, and renal function test were normal. A radiographic examination of the related skeleton demonstrated multiple osteochondromas of scapula and tibia fibula. As a consequence of mutations in the Exostosin 1 and Exostosin 2 genes, chondrocytes exhibiting shortened Heparan Sulfate chains are present in this region. In the later stages, these cells develop exostoses. Multiple Hereditary Exostoses may involve different bone locations and could be diagnosed using various medical imaging modalities, however plain radiography x-ray was already sufficient enough to conclude the abnormality. Sessile lesions were much more common than pedunculated in Multiple Hereditary Exostoses, however Sessile lesions bear a higher risk of malignant transformation into chondrosarcoma. Upon early detection, the prognosis for patients who have chondrosarcoma was favorable. Multiple Hereditary Exostoses is a rare bone disorder marked by the development of non-cancerous tumors near the growth plates of bones. This condition can greatly affect an individual's quality of life, resulting in restricted mobility, skeletal abnormalities, ongoing pain, inhibited growth, and the risk of the exostoses becoming malignant.

Утомленность, психическое состояние и настроение сотрудников органов внутренних дел

The article discusses the relationship between fatigue and the peculiarities of the mental state of ATS employees, including discussing which types of moods are dominant among ATS employees with different values of fatigue. The study involved 470 employees of the Department of Internal Affairs who underwent initial training and advanced training at the St. Petersburg University of the Ministry of Internal Affairs of Russia (312 male employees, 158 female employees with service experience from 1 year to 15 years). The following psychodiagnostic techniques were used: the questionnaire "Determination of the dominant state" (L. V. Kulikov), the questionnaire "Subjective assessment of the level of fatigue of the individual" (S. V. Dukhnovsky, E. K. Shelepina). During the correlation analysis, significant relationships were established between the fatigue indicator (according to the method of "Subjective assessment of the level of fatigue of the individual") and such parameters of the dominant mental state as "active (passive) attitude to the situation", "cheerfulness (despondency)", "high (low) tone", "looseness (tension)", as well as "life satisfaction" according to the method of "Determining the dominant state". During the comparative analysis, significant differences in the characteristics of the mental state of police officers with different values of fatigue were established. Among other things, it was found that for employees of the Department of Internal Affairs with low fatigue values, the dominant types of mood will be "inspired" and "prosperous"; with moderate values - "active"; and with high values - "sad (melancholic)".

The India-China-USA Triangle in South Asia and Russia

The article examines the transformation of South Asia, highlighting the distinctive characteristics of the foreign policy strategies of major powers, the interplay between regionalization and globalization, and the prospects for either confrontation or interdependence among the region’s dominant states. South Asia is currently undergoing multifaceted and ambiguous repercussions of significant geopolitical shifts, underscoring the growing importance of analyzing the contemporary phase of interstate relations in this region. South Asia, in many ways, mirrors the broader global changes but on a smaller scale. The region comprises countries with stark disparities in territory, population, economic capacity, scientific and technological advancement, military power, as well as cultural and civilizational traits – all of which significantly shape interstate relations. India’s dominance within the region fosters distrust among its neighbors and exacerbates their perception of vulnerability. Consequently, these states increasingly seek to strengthen their positions in both regional and international arenas by leveraging relationships with extra-regional powers, most notably China. Moreover, unresolved disputes with India are frequently brought to the attention of the international community. The article also addresses the impact of external factors on South Asia’s international relations system, focusing on the substantial shifts in the strategies of major powers following the Cold War. It explores key issues such as the Indian-Chinese rivalry in the region, the United States’ adverse influence, and Russia’s policy toward South Asia.

Short-term outcomes of gradual ulnar lengthening in multiple hereditary osteochondromas of the forearm with monolateral external fixator.

Hereditary multiple exostoses is an autosomal dominant genetic condition primarily affecting long bones. Forearm deformities, including wrist ulnar deviation, ulnar shortening, radial or ulnar bowing, and radial head dislocation, are common manifestations. Gradual ulnar lengthening is suggested as a viable treatment option for managing these deformities. This retrospective single-center study included 15 forearms treated with gradual ulnar lengthening using a monolateral external fixator by a single surgeon. Clinical and radiological characteristics were recorded preoperatively and during follow-ups. The Wilcoxon signed-rank test compared preoperative and postoperative radiological and clinical parameters, while McNemar's test assessed changes in radial head dislocation or subluxation. Significant radiological improvements were observed post-treatment. Proportional ulnar length increased from a mean of 0.85 ± 0.10 preoperatively to 1.11 ± 0.03 at the last follow-up (P < 0.001). Ulnar variance decreased from a mean of 17.6 ± 5.58 mm preoperatively to 0.13 ± 1.81 mm at the last follow-up (P < 0.001), while radial bowing decreased from a mean of 0.06 ± 0.02 to 0.05 ± 0.01 at the last follow-up (P < 0.001). In addition, the radioarticular angle decreased significantly from a mean of 29.93 ± 7.34 to 20.20 ± 5.71° (P < 0.001). The incidence of radial head dislocation or subluxation decreased significantly, from 11 patients preoperatively to only one at the last follow-up. These findings demonstrate the effectiveness of gradual ulnar lengthening with a monolateral external fixator in correcting forearm deformities and reducing the incidence of radial head dislocation or subluxation.

How does forest fertilization influence tree productivity of boreal forests? An analysis of data from commercial forestry across Sweden.

Forest fertilization is a forest management practice that is often claimed to increase productivity in boreal forests. Although regarded as an efficient way to increase profitability, it is also costly, and associated with risks such as biodiversity loss and nitrogen leaching from the soil. To be both cost-efficient and sustainable, potential enhanced productivity due to fertilization should be balanced against the adverse environmental impact. One effective strategy is to limit fertilization to sites where it can most significantly increase tree productivity, while avoiding application in less suitable areas. However, the current understanding of the specific conditions under which forest fertilization optimally stimulates tree growth is limited. To clarify this, we analysed standing tree volume from 32,498 recently harvested fertilized and unfertilized stands from Sweden's largest forest owner. We applied generalized additive models to quantify the effect of fertilization on standing tree volume at harvest and how the fertilization effect depended on dominant tree species, stand characteristics (site index, stem density), climatic conditions (temperature sum), and management (thinning, stand age at harvest). We found that the effect of operational fertilization was highly context-dependent. In pine-dominated stands, fertilization failed to increase tree volumes in cold climates and low-productive stands. In spruce-dominated stands, fertilization did not result in increased tree volumes in low-productive and high-productive stands. For a more sustainable and cost-efficient application of this practice we suggest that the context dependency of the efficiency of fertilization is given more attention. Hence, we recommend to refrain from fertilizing pine-dominated stands situated on low-productive land or in regions with cold climates, such as those found in northern Sweden.

Антистресс-обучение медицинских работников скорой помощи: возможности, направления, оценка эффективности

&lt;p&gt;The work is &lt;strong&gt;aimed&lt;/strong&gt; at finding technologies to protect professionals from the ever-increasing negative stressors of their life and professional environment. The objective of the study was to evaluate the effectiveness of a short-term anti-stress training program for emergency medical workers. The study &lt;strong&gt;participants&lt;/strong&gt; included employees of several emergency medical teams (n = 30, 73% women, 27% men; age 27&amp;ndash;42 years (M = 32.2)) divided into an experimental (n = 15, 80% women, 20% men) and a control (n = 15, 67% women, 33% men) group. The study included two diagnostic measurements of the current state, stress level, and burnout of specialists before and after (10 days later) the &lt;em&gt;anti-stress training program&lt;/em&gt;, which included 7 1.5-hour sessions over 14 days. The &lt;strong&gt;methods&lt;/strong&gt; used were: &amp;ldquo;The scale-thermometer of self-assessment of the current state&amp;rdquo; (A.O. Prokhorov), Methodology for assessing the dominant state (DS-6 by L.V. Kulikova), Differential diagnostics of states of reduced performance (DORS by A.B. Leonova and S.B. Velichkovskaya), burnout test by K. Maslach (adaptation by Vodopyanova), stress level test by V.Yu. Shcherbatykh (2022 version). The &lt;strong&gt;results&lt;/strong&gt; obtained indicate an improvement in the activity and performance indicators of the participants in anti-stress training, an increase in the subjective value of the activity and their contribution to the profession, a decrease in the level of fatigue, emotional and physiological manifestations of stress. &lt;strong&gt;Conclusion&lt;/strong&gt;: the effectiveness of not only long-term but also short-term anti-stress training has been demonstrated, with a systematic organization of mastering the skills of self-regulation and personal resource growth.&lt;/p&gt;

Green Pan-Africanism: Normative power and the making of a regional sustainability order

Abstract This article examines the role of normative power in shaping the global sustainability order. It challenges the prevailing focus on hegemonic leadership and norm diffusion from dominant states, arguing that less powerful states have contributed significantly to the global order by creating regional initiatives tailored to their unique contexts. The article adopts an alternative theoretical framework of norm-governed change, comprising norm-building, institutionalisation, and transformation. Using an illustrative case study of Africa’s regional economic institutions, it employs process-tracing and archival analysis of key policy documents. The study demonstrates how African states have proactively embedded environmental norms within their regional initiatives, while contributing to the global sustainability agenda, exemplifying a form of normative power referred to as ‘Green Pan-Africanism’. This approach broadens the understanding of global sustainability governance, positioning less economically powerful actors as active participants in world-making. The findings highlight the critical role of normative power in advancing global sustainability governance, particularly in addressing complex global challenges such as climate change.

Patients' perspectives regarding health professionals contacting their relatives about genetic risk directly (with patient consent).

Genetic testing of blood relatives of individuals at high risk of dominant conditions has significant preventive health benefits. However, cascade testing uptake is <50%. Research shows increased testing uptake when health professionals (HPs) contact at-risk relatives directly, with patient consent. Despite international support, this is not standard practice in Australia. We aimed to gather perspectives of genetic testing patients about direct-contact methods. Using an online survey, we surveyed Australian adults with genetic results of relevance for relatives, including patients who (i) self-categorised as being directly contacted by a clinical service, (ii) self-categorised as being referred by a HP, and (iii) received genetic results through a research study. Overall, 442 patients responded (clinical n = 363; research n = 79). Clinical patients self-categorised as 49.0% directly-contacted and 51.0% referred. Overall, the majority of patients had no privacy concerns about direct-contact methods (direct-contact 97%; referred 77%; research 76%). Less than 5% of the combined cohort (n = 19/442) reported significant concerns. The most prevalent concerns were the need for consent to provide HPs with relatives' contact details, and a patient preference to notify relatives before HP contact. Other key findings include preferences about contact methods, including that most patients who received a letter from a genetics service preferred a letter with specific information about the familial genetic condition (n = 141/149; 94.6%) than one with general information about genetic risk. Our findings indicate Australian patients support HPs using direct-contact methods to assist with risk communication to relatives. Findings also identify concerns to be addressed in the design of direct-contact programs.

Nonlinear vibration characteristics of size-dependent moving microbeams considering axial forces

Abstract This paper investigates the nonlinear vibration behavior of viscoelastic microbeams under axial velocity, incorporating both nonlocal strain gradient theory and the microelement method to establish governing equations. Wickert’s quasi-static assumption is utilized for comparison with the effects of classical nonlocal axial forces. Numerical simulations of the natural frequency, mode function, and stability reveal that the linear vibration of the microbeam is scale-dependent. Under the conditions of nonlocal parameter dominance selected herein, the critical velocities of divergence and flutter decrease by 23.1% and 46.0%, respectively, while the dominance of the material&amp;#xD;characteristic length parameter increases them by 43.1% and 141.10%, respectively, and the velocity interval of the flutter instability is also affected by the scale parameter. Additionally, the nonlinear frequency is analyzed using the direct multiscale method, showing that the nonlinear effect varies with scale and is dependent on the nonlinear characteristics of the model. Specifically, the model based on classical nonlocal axial force is more sensitive to changes in the material characteristic length parameter, while the model incorporating Wickert’s quasi-static hypothesis is more sensitive to the nonlocal parameter.

R(3780) Resonance Interpreted as the 1D13 -Wave Dominant State of Charmonium from Precise Measurements of the Cross Section of e+e−→Hadrons

We report the precise measurements of the cross section of e+e−→hadrons at center-of-mass energies from 3.645 to 3.871 GeV. We thereby perform the most precise study of the cross sections and find a complex system composed of three resonances of R(3760), R(3780), and R(3810). For the first time, we measure the R(3810) electronic width to be (19.4±7.4±12.1) eV. For the R(3760) resonance, we measure the mass to be (3751.9±3.8±2.8) MeV/c2, the total width to be (32.8±5.8±8.7) MeV, and the electronic width to be (184±75±86) eV. For the R(3780) resonance, we measure its mass to be (3778.7±0.5±0.3) MeV/c2, total width to be (20.3±0.8±1.7) MeV, and electronic width to be (265±67±83) eV. Forty-seven years ago, the ψ(3770) resonance was discovered, and was subsequently interpreted as the 1D13-wave dominant state of charmonium. However, our analysis of the total-hadron cross sections indicates that the ψ(3770) is not a single state, but a complex system composed of the R(3760), R(3780), and R(3810) resonances. Among these, we interpret the R(3780) is a resonance dominated by the 1D13 charmonium state. Published by the American Physical Society 2024

‘Good’ citizens or ‘faithful’ Muslims? Contested narratives for citizenship education in Pakistan

ABSTRACT One of the key objectives of citizenship education is to prepare future citizens who will meet the needs and the vision of their respective nations. In Pakistan, state-developed curricula are suffused with aspirations for developing both faithful Muslims and good citizens. This article is concerned with the ways teachers make sense of this official discourse equating faithful Muslims with good citizens. It uses thematic analysis to explore the in-depth perspectives of sixteen teachers of Pakistan Studies concerning the dominant state narrative. The findings show that teachers’ conceptualization of being a ‘good’ citizen is not consistent with the state narrative. Instead, the idea of a ‘good’ citizen is understood in a secular sense by many teachers. The focus is on developing personally responsible citizens albeit with little consideration for an explicit political role.

Flat Friedmann-Lemaitre-Robertson-Walker Cosmological Model with Time-Dependent Cosmological Constant in Brans-Dicke Theory of Gravity

Recently, there has been much interest in investigating outstanding problems of cosmology with modified theories of gravity. The Brans-Dicke theory of gravity is one such theory developed by Brans and Dicke absorbing Mach’s principle into the General Theory of Relativity. In Brans-Dicke theory, gravity couples with a time-dependent scalar field ϕ through a coupling parameter ω. This theory reduces to the General Theory of Relativity if the scalar field ϕ is constant and the coupling parameter ω →∞. In this paper, we consider a flat Friedmann-Lemaıtre-Robertson-Walker (FLRW) universe with a time-dependent cosmological constant in Brans-Dicke theory of gravity. Exact solutions of the field equations are obtained by using a power law relation between the scale factor and the Brans-Dicke scalar field ϕ and by taking the Hubble parameter H to be a hyperbolic function of the cosmic time t. We study the cosmological dynamics of our model by graphically representing some important cosmological parameters such as the deceleration parameter, energy density parameter, equation of state parameter, jerk parameter, snap parameter, lerk parameter etc. The statefinder diagnostic pair of the model is also obtained and the validity of the four energy conditions, viz. the Strong energy condition (SEC), Weak energy condition (WEC), Dominant energy condition (DEC) and Null energy condition (NEC), is examined. We find that the universe corresponding to our model is expanding throughout its evolution and exhibits late time cosmic acceleration, which is in agreement with the current observational data.

A qualitative study of perceptions of the care pathway for familial hypercholesterolemia: screening, diagnosis, treatment, and family cascade screening

BackgroundFamilial hypercholesterolemia (FH) is an autosomal dominant genetic condition that carries increased risk for premature atherosclerotic cardiovascular disease, cardiovascular events, and death. Due to low uptake of evidence-based practices, up to 80% of FH patients remain undiagnosed and most are undertreated. This project aimed to understand patient and clinician perceptions across the care pathway of evidence-based diagnosis and treatment of FH, to inform implementation strategy design for two clinical trials seeking to increase evidence-based care.MethodsWith input from FH experts, we identified key points along the FH care pathway that might be targeted with broad-scale implementation efforts, including: (a) identification of the need for screening; (b) completion of screening test(s); (c) diagnosis; (d) connection to treatment; and (e) family cascade screening (a process used to identify and screen relatives of individuals diagnosed with FH). Then, we conducted qualitative interviews with patients who had participated in a prior FH quality improvement initiative and with clinicians who treat high cholesterol. We analyzed data using thematic analysis.ResultsWe interviewed 21 patients and 17 clinicians. Patient themes offered insights related to the impact of family history, reactions to a diagnosis of high cholesterol and/or FH, experiences with FH treatment and clinical care, perceptions of tools to diagnose FH, motivations and preferences for FH screening efforts, and reactions to family screening. Clinician themes offered insights into the perceived value of FH screening and diagnosis, current FH-related practice and context, and attitudes toward tools to aid clinical practice. In both sets of interviews, confusion and misconceptions about what makes FH unique and its clinical implications were common, as were concerns about logistics and competing priorities.ConclusionQualitative inquiry generated insights into several modifiable patient and clinician determinants of engagement with evidence-based implementation along the FH care pathway, many of which can be targeted with behavioral economics strategies that simplify complex decisions and by addressing informational and emotional needs. These findings offer actionable insights to inform future implementation research that seeks to close the evidence-to-practice gap in diagnosis and delivery of evidence-based care for FH.