Electron Imaging of Nanoscale Charge Distributions Induced by Femtosecond Light Pulses.

Surface charging is ubiquitously observable during in situ transmission electron microscopy of nonconducting specimens as a result of electron beam/sample interactions or optical stimuli and often limits the achievable image stability and spatial or spectral resolution. Here, we report on the electron-optical imaging of surface charging on a nanostructured surface following femtosecond multiphoton photoemission. By quantitatively extracting the light-induced electrostatic potential and studying the charging dynamics on relevant time scales, we gain insights into the details of the multiphoton photoemission process in the presence of an electrostatic background field. We study the interaction of the charge distribution with the high-energy electron beam and secondary electrons and propose a simple model to describe the interplay of electron- and light-induced processes. In addition, we demonstrate how to mitigate sample charging by simultaneously optically illuminating the sample.

Inversion recovery and saturation recovery pulmonary vein MR angiography using an image based navigator fluoro trigger and variable-density 3D cartesian sampling with spiral-like order.

Contrast enhanced pulmonary vein magnetic resonance angiography (PV CE-MRA) has value in atrial ablation pre-procedural planning. We aimed to provide high fidelity, ECG gated PV CE-MRA accelerated by variable density Cartesian sampling (VD-CASPR) with image navigator (iNAV) respiratory motion correction acquired in under 4 min. We describe its use in part during the global iodinated contrast shortage. VD-CASPR/iNAV framework was applied to ECG-gated inversion and saturation recovery gradient recalled echo PV CE-MRA in 65 patients (66 exams) using .15 mmol/kg Gadobutrol. Image quality was assessed by three physicians, and anatomical segmentation quality by two technologists. Left atrial SNR and left atrial/myocardial CNR were measured. 12 patients had CTA within 6 months of MRA. Two readers assessed PV ostial measurements versus CTA for intermodality/interobserver agreement. Inter-rater/intermodality reliability, reproducibility of ostial measurements, SNR/CNR, image, and anatomical segmentation quality was compared. The mean acquisition time was 3.58 ± 0.60 min. Of 35 PV pre-ablation datasets (34 patients), mean anatomical segmentation quality score was 3.66 ± 0.54 and 3.63 ± 0.55 as rated by technologists 1 and 2, respectively (p = 0.7113). Good/excellent anatomical segmentation quality (grade 3/4) was seen in 97% of exams. Each rated one exam as moderate quality (grade 2). 95% received a majority image quality score of good/excellent by three physicians. Ostial PV measurements correlated moderate to excellently with CTA (ICCs range 0.52-0.86). No difference in SNR was observed between IR and SR. High quality PV CE-MRA is possible in under 4 min using iNAV bolus timing/motion correction and VD-CASPR.

Etiologies and Impact of Exclusion Rates for Transcatheter Mitral and Tricuspid Valve Structural Heart Clinical Trials at a High-Volume Quaternary Care Hospital.

There are various devices under clinical investigation for transcatheter mitral valve intervention and transcatheter tricuspid valve intervention (TTVI); however, the exclusion rates remain high. We aimed to investigate the exclusion rates for transcatheter mitral valve repair (TMVr), transcatheter mitral valve replacement (TMVR), transcatheter tricuspid valve repair (TTVr), and transcatheter tricuspid valve replacement (TTVR). There were 129 patients who were referred to St. Francis Hospital & Heart Center valve clinic and completed screening between January 2021 and July 2022. The causes for exclusion were classified into 4 categories: patient withdrawal, anatomic unsuitability, clinical criteria, and medical futility. In 129 patients, the exclusion rates for TMVr, TMVR, TTVr, and TTVR were 81%, 85%, 91%, and 87%, respectively. Patient withdrawal and medical futility were leading etiologies for exclusion, followed by anatomic unsuitability. TMVr had the highest rate of patient withdrawal (64%) and the lowest anatomic unsuitability (5%) because of short posterior leaflet length. Replacement interventions have a higher anatomic unsuitability (33%) than repair interventions (17%) (p = 0.04). Most exclusions of anatomic unsuitability were because of mitral stenosis or small annulus size for TMVR and large annulus size for TTVR. A total of 50% of exclusions from TTVr were because of the presence of pacemaker/defibrillator leads. In patients excluded from their respective trials, patients being referred for TMVr had the highest recurrent hospitalization and repair group had a higher mortality (p <0.01 and p = 0.01, respectively). In conclusion, the exclusion rates for transcatheter mitral valve intervention and TTVI trials remain high because of various reasons, limiting patient enrollment and treatment. This supports the need for further device improvement or exploring alternative means of therapy.

Association of pulmonary transit time by cardiac magnetic resonance with heart failure hospitalization in a large prospective cohort with diverse cardiac conditions.

BACKGROUND: Longer pulmonary transit time (PTT) is closely associated with hemodynamic abnormalities. However, the implications on heart failure (HF) risk have not been investigated broadly in patients with diverse cardiac conditions. In this study we examined the long-term risk of HF hospitalization associated with longer PTT in a large prospective cohort with a broad spectrum of cardiac conditions. METHODS: All subjects were prospectively recruited to undergo cardiac magnetic resonance (CMR). The dynamic images of first-pass perfusion were acquired to assess peak-to-peak pulmonary transit time (PTT) which was subsequently normalized to RR interval duration. The risk of HF was examined using Cox proportional hazards models adjusted for baseline confounding risk factors. RESULTS: Among 506 consecutively consented patients undergoing clinical cardiac MR with diverse cardiac conditions, the mean age was 63 ± 14 years and 373 (73%) were male. After a mean follow up duration of 4.5 ± 3.0 years, 70 (14%) patients developed hospitalized HF and of these 6 died. A normalized PTT ≥ 8.2 was associated with a significantly increased adjusted HF hazard ratio of 3.69 (95% CI 2.02, 6.73). The HF hazard ratio was 1.26 (95% CI 1.18, 1.33) for each 1 unit increase in PTT which was higher among those preserved (1.70, 95% CI 1.20, 2.41) compared to those with reduced left ventricular ejection fraction (< 50%) (1.18, 95% CI 1.09, 1.27). PTT remained a significant risk factor of hospitalized HF after additional adjustment for N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) or left ventricular global longitudinal strain with additionally demonstrated incremental model improvement through likelihood ratio testing. CONCLUSIONS: Our findings support the role of PTT in assessing HF risk among patients with broad spectrum of cardiac conditions with reduced as well as preserved ejection fraction. Longer PTT duration is an incremental risk factor for HF when baseline global longitudinal strain and NT-proBNP are taken into consideration.

Comparison between compressed sensing and segmented cine cardiac magnetic resonance: a meta-analysis.

PURPOSE: Highly accelerated compressed sensing cine has allowed for quantification of ventricular function in a single breath hold. However, compared to segmented breath hold techniques, there may be underestimation or overestimation of LV volumes. Furthermore, a heterogeneous sample of techniques have been used in volunteers and patients for pre-clinical and clinical use. This can complicate individual comparisons where small, but statistically significant differences exist in left ventricular morphological and/or functional parameters. This meta-analysis aims to provide a comparison of conventional cine versus compressed sensing based reconstruction techniques in patients and volunteers. METHODS: Two investigators performed systematic searches for eligible studies using PubMed/MEDLINE and Web of Science to identify studies published 1/1/2010-3/1/2021. Ultimately, 15 studies were included for comparison between compressed sensing cine and conventional imaging. RESULTS: Compared to conventional cine, there were small, statistically significant overestimation of LV mass, underestimation of stroke volume and LV end diastolic volume (mean difference 2.65 g [CL 0.57-4.73], 2.52 mL [CL 0.73-4.31], and 2.39 mL [CL 0.07-4.70], respectively). Attenuated differences persisted across studies using prospective gating (underestimated stroke volume) and non-prospective gating (underestimation of stroke volume, overestimation of mass). There were no significant differences in LV volumes or LV mass with high or low acceleration subgroups in reference to conventional cine except slight underestimation of ejection fraction among high acceleration studies. Reduction in breath hold acquisition time ranged from 33 to 64%, while reduction in total scan duration ranged from 43 to 97%. CONCLUSION: LV volume and mass assessment using compressed sensing CMR is accurate compared to conventional parallel imaging cine.

Left Ventricular Mass, Myocardial Structure, and Function in Severe Aortic Stenosis: an Echocardiographic and Cardiac Magnetic Resonance Imaging Study.

In severe aortic stenosis (AS), there are conflicting data on the prognostic implications of left ventricular (LV) hypertrophy (LVH). We aimed to characterize the LV geometry, myocardial matrix structural changes, and prognostic stratification using cardiac magnetic resonance imaging (CMR) and echocardiography in subjects with severe AS with and without LVH. Consecutive patients who had severe isolated AS and sufficient quality echocardiography and CMR within 6 months of each other were evaluated for LVH, cardiac structure, morphology, and late gadolinium-enhancement imaging. Kaplan-Meier curves, linear models, and proportional hazards models were used for prognostic stratification. There were 93 patients enrolled (mean age 74 ± 11 years, 48% female), of whom 38 (41%) had a normal LV mass index (LVMI), 41 (44%) had LVH defined at CMR by LVMI >2 SD higher than normal, and 14 (15% of the total) with >4 SD higher than the reference LVMI (severely elevated). The Society of Thoracic Surgeons scores were similar among the LVMI groups. Compared with those with normal LVMI, patients with LVH had higher LV end-diastolic and end-systolic volumes, increased late gadolinium-enhancement burden, and lower LV ejection fraction. Most notably, CMR feature-tracking global radial strain, 2-dimensional speckle-tracking echocardiography global longitudinal strain, and left atrial reservoir function were significantly worse. On the survival analyses, LVMI was not associated with a composite of all-cause mortality and/or heart failure hospitalization. In conclusion, compared with normal LVMI, elevated LVMI was not associated with a higher risk of adverse outcomes.

Religion, spirituality and improved glycemic control among people with type 2 diabetes: A systematic review.

OBJECTIVE: This systematic review investigates the association between measures of religiosity or spirituality (R/S) and glycemic control in patients with type 2 diabetes. METHODS: A systematic literature review was conducted for all English language articles published between 1966 and August 2022 in six relevant databases: PubMed, PSYCHinfo, CINAHL, ATLA, Scopus, Sociological Abstracts, and the Cochrane Central Register of Controlled Clinical Trials. Search terms for religious variables included, "religion", "religiosity", "spirituality", "religious attendance". Search terms for diabetes outcomes included, "diabetes", "hemoglobin A1c", "blood glucose", "glycemic control." The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). RESULTS: A total of 758 studies examining correlations between R/S and glycemic control were screened from relevant databases. Forty studies were evaluated for eligibility and inclusion. Eight studies were selected and analyzed. Three studies showed positive associations, two studies showed positive and neutral associations, two studies showed positive and negative associations, and one study showed a neutral association. Limitations included small sample sizes and heterogeneity of study designs. CONCLUSION: Involvement in religious and spiritual practices may be associated with improved glycemic control in patients with type 2 diabetes. Specific mechanisms for associations may be partially explained by more effective self-management practices, increased positive social contacts, and regular community support. Further research is needed to clarify these associations.

LSTM-Based Projectile Trajectory Estimation in a GNSS-Denied Environment.

This paper presents a deep learning approach to estimate a projectile trajectory in a GNSS-denied environment. For this purpose, Long-Short-Term-Memories (LSTMs) are trained on projectile fire simulations. The network inputs are the embedded Inertial Measurement Unit (IMU) data, the magnetic field reference, flight parameters specific to the projectile and a time vector. This paper focuses on the influence of LSTM input data pre-processing, i.e., normalization and navigation frame rotation, leading to rescale 3D projectile data over similar variation ranges. In addition, the effect of the sensor error model on the estimation accuracy is analyzed. LSTM estimates are compared to a classical Dead-Reckoning algorithm, and the estimation accuracy is evaluated via multiple error criteria and the position errors at the impact point. Results, presented for a finned projectile, clearly show the Artificial Intelligence (AI) contribution, especially for the projectile position and velocity estimations. Indeed, the LSTM estimation errors are reduced compared to a classical navigation algorithm as well as to GNSS-guided finned projectiles.

Optimization and validation of an ELISA assay for the determination of antibody responses to CN54gp140 and AIDSVAX BE for use in the Phase IIb PrEPVacc vaccine trial.

PrEPVacc is an international, multi-centre, double-blind vaccine study comparing experimental combination vaccine regimens including DNA/AIDSVAX BE and DNA/CN54gp140 with placebo control. Simultaneously, daily oral PrEP is compared for efficacy against daily Truvada in the context of the current PrEP availability situation at the study sites. An important clinical trial outcome is the accurate measurement of in vivo antibody titer induced through vaccination. Here we report the validation of two ELISAs for CN54gp140 and AIDSVAX BE at Uganda Virus Research Institute that demonstrates precision, specificity, and robustness for assessing the reciprocal antibody end point titer in human serum. This is a critical endpoint for determining whether vaccination can provide any protection against HIV in populations at risk of acquiring HIV.

Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context.

Fibrosis is a progressive biological condition, leading to organ dysfunction in various clinical settings. Although fibroblasts and macrophages are known as key cellular players for fibrosis development, a comprehensive functional model that considers their interaction in the metabolic/immunologic context of fibrotic tissue has not been set up. Here we show, by transcriptome-based mathematical modeling in an in vitro system that represents macrophage-fibroblast interplay and reflects the functional effects of inflammation, hypoxia and the adaptive immune context, that irreversible fibrosis development is associated with specific combinations of metabolic and inflammatory cues. The in vitro signatures are in good alignment with transcriptomic profiles generated on laser captured glomeruli and cortical tubule-interstitial area, isolated from human transplanted kidneys with advanced stages of glomerulosclerosis and interstitial fibrosis/tubular atrophy, two clinically relevant conditions associated with organ failure in renal allografts. The model we describe here is validated on tissue based quantitative immune-phenotyping of biopsies from transplanted kidneys, demonstrating its feasibility. We conclude that the combination of in vitro and in silico modeling represents a powerful systems medicine approach to dissect fibrosis pathogenesis, applicable to specific pathological conditions, and develop coordinated targeted approaches.

Arabidopsis PFA-DSP-Type Phosphohydrolases Target Specific Inositol Pyrophosphate Messengers.

Inositol pyrophosphates are signaling molecules containing at least one phosphoanhydride bond that regulate a wide range of cellular processes in eukaryotes. With a cyclic array of phosphate esters and diphosphate groups around myo-inositol, these molecular messengers possess the highest charge density found in nature. Recent work deciphering inositol pyrophosphate biosynthesis in Arabidopsis revealed important functions of these messengers in nutrient sensing, hormone signaling, and plant immunity. However, despite the rapid hydrolysis of these molecules in plant extracts, very little is known about the molecular identity of the phosphohydrolases that convert these messengers back to their inositol polyphosphate precursors. Here, we investigate whether Arabidopsis Plant and Fungi Atypical Dual Specificity Phosphatases (PFA-DSP1-5) catalyze inositol pyrophosphate phosphohydrolase activity. We find that recombinant proteins of all five Arabidopsis PFA-DSP homologues display phosphohydrolase activity with a high specificity for the 5-ß-phosphate of inositol pyrophosphates and only minor activity against the ß-phosphates of 4-InsP7 and 6-InsP7. We further show that heterologous expression of Arabidopsis PFA-DSP1-5 rescues wortmannin sensitivity and deranged inositol pyrophosphate homeostasis caused by the deficiency of the PFA-DSP-type inositol pyrophosphate phosphohydrolase Siw14 in yeast. Heterologous expression in Nicotiana benthamiana leaves provided evidence that Arabidopsis PFA-DSP1 also displays 5-ß-phosphate-specific inositol pyrophosphate phosphohydrolase activity in planta. Our findings lay the biochemical basis and provide the genetic tools to uncover the roles of inositol pyrophosphates in plant physiology and plant development.

Systematic comparison of HIV-1 Envelope-specific IgG responses induced by different vaccination regimens: Can we steer IgG recognition towards regions of viral vulnerability?

Immunogens and vaccination regimens can influence patterns of immune-epitope recognition, steering them towards or away from epitopes of potential viral vulnerability. HIV-1 envelope (Env)-specific antibodies targeting variable region 2 (V2) or 3 (V3) correlated with protection during the RV144 trial, however, it was suggested that the immunodominant V3 region might divert antibody responses away from other relevant sites. We mapped IgG responses against linear Env epitopes in five clinical HIV vaccine trials, revealing a specific pattern of Env targeting for each regimen. Notable V2 responses were only induced in trials administering CRF01_AE based immunogens, but targeting of V3 was seen in all trials, with the soluble, trimeric CN54gp140 protein eliciting robust V3 recognition. Strong V3 targeting was linked to greater overall response, increased number of total recognised antigenic regions, and where present, stronger V2 recognition. Hence, strong induction of V3-specific antibodies did not negatively impact the targeting of other linear epitopes in this study, suggesting that the induction of antibodies against V3 and other regions of potential viral vulnerability need not be necessarily mutually exclusive.

Low Adrenomedullary Function Predicts Acute Illness in Infants With Classical Congenital Adrenal Hyperplasia.

CONTEXT: Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. OBJECTIVE: This work aimed to study plasma epinephrine levels in infants with classical CAH and examine the clinical significance of epinephrine deficiency in the first year of life. METHODS: This prospective cohort study comprised participants recruited from a pediatric tertiary care center: 36 infants with classical CAH due to 21-hydroxylase deficiency and 27 age-matched unaffected controls with congenital hypothyroidism. Main outcome measures included plasma epinephrine levels (N = 27), CYP21A2 genotype (N = 15), and incidence of acute illnesses from birth to age 1 year (N = 28). RESULTS: Epinephrine levels in CAH infants independently predicted illness incidence in the first year of life (ß = -0.018, R = -0.45, P = .02) and were negatively correlated with 17-hydroxyprogesterone at diagnosis (R = -0.51, P = .007). Infants with salt-wasting CAH exhibited lower epinephrine levels as newborns than simple-virilizing infants (P = .02). CAH patients had lower epinephrine as newborns than did controls (P = .007) and showed decreases in epinephrine from birth to age 1 year (P = .04). Null genotype was associated with lower newborn epinephrine and more illness in the first year of life, compared to less severe mutation categories. CONCLUSION: Lower epinephrine levels are associated with increased risk of illness among CAH infants. While not currently part of clinical standard of care, measuring epinephrine levels and assessing genotype may help predict acute illness in the first year of life.

Comparing left atrial indices by CMR in association with left ventricular diastolic dysfunction and adverse clinical outcomes.

Left atrial (LA) features are altered when diastolic dysfunction (DD) is present. The relations of LA features to the DD severity and to adverse outcomes remain unclear using CMR images. We sought to compare LA features including volumes, emptying fraction, and strains as predictors of left ventricular (LV) DD and adverse outcomes. We compared four groups including normal controls (n = 32), grade I DD (n = 69), grade II DD (n = 42), and grade III DD (n = 21). DD was graded by echocardiography following the current ASE guidelines. Maximum LA volume (LAVmax), minimum LA volume (LAVmin), and LA emptying fraction (LAEF) were assessed using CMR cine images. Phasic LA strains including reservoir, conduit, and booster pump strain were assessed by feature tracking. The outcome was a composite of hospital admissions for heart failure and all-cause mortality analyzed using Cox proportional hazard models. LAVmax and LAVmin were progressively larger while LAEF and LA strain measures were lower with worsening degree of DD (all p < 0.001). Among 132 patients with DD, 61 reached the composite outcome after on average 36-months of follow-up. Each of the LA parameters except for LA conduit strain was an independent predictor of the outcome in the adjusted Cox proportional hazard models (all p < 0.001). They remained significant outcome predictors after the model additionally adjusted for LV longitudinal strain. The AUC of outcome prediction was highest by LAEF (0.760) followed by LA reservoir strain (0.733) and LAVmin (0.725). Among all the LA features, increased LA volumes, reduced LAEF, reduced LA reservoir and booster pump strains were all associated with DD and DD severity. While LA strains are valuable, conventional parameters such as LAEF and LAVmin remain to be highly effective in outcome prediction with comparable performance.

Utility of compression immediately after venous closure: Does it matter?

BACKGROUND: Leg compression after venous closures for 24-48 hours or longer is commonplace and controversial. OBJECTIVE: The goal of our study was to evaluate compression immediately post-venous closures and its associated costs. METHODS: Records were retrospectively reviewed after consecutive therapies of sclerotherapy, mechanochemical ablation (MOCA) & radiofrequency ablation (RFA) from 1 clinic with 2 cohorts: 7/2/13-10/15/15 were immediately ACE-wrapped for 3-5 days (AW, N = 52) and 10/20/15-1/5/16 were non ACE-wrapped (NAW, N = 49). All procedures were performed in an outpatient office setting of one surgeon (P.L.). Follow-up was within 1 week and 3 months with ultrasounds. Financial data of ACE wraps and ABD pads were assessed. RESULTS: Closures consisted of consecutive therapies of sclerotherapy (4 patients); MOCA (44 patients) and RFA (53 patients). No statistical difference existed in age (p = 0.61), sex (p = 0.2063); race (0.3689), CAD (p = 0.1442), ESRD (p = 0.2914), diabetes mellitus (p = 0.8943), hypertension (p = 0.681), COPD (p = 0.38), or smoking (p = 0.3628). NAW group had higher rate of hyperlipidemia (p = 0.0225), obesity (p = 0.0283), MOCA and sclerotherapy (p = 0.0005). No difference existed in pain (p = 0.8897); wound complications were too small to perform analysis; and swelling was greater in AW group compared to NAW group (p = 0.0132, OR 3.3951, CI 1.269; 9.0834). Closure rates were 98% and 100% in AW and NAW groups, respectively. NAW were only a total cost savings of $1.58 per leg per procedure. CONCLUSION: AW for compression after vein closures confers no benefit in postoperative period with no effect on closure rates; may be associated with increased swelling, discomfort, and wound complications while increasing unnecessary and negligible monetary costs. Larger sample size is needed to validate these conclusions.

The association of reduced left ventricular strains with increased extracellular volume and their collective impact on clinical outcomes.

BACKGROUND: Myocardial fibrosis and left ventricular (LV) longitudinal strain are independently associated with adverse clinical outcomes. However, the relationship between tissue properties and strain indices as well as their collective impact on outcomes are yet to be fully elucidated. We aim to investigate the relationship between LV global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) with extracellular volume (ECV) and their collective impact. METHODS: Consecutive patients referred for clinical cardiovascular magnetic resonance (CMR) due to cardiomyopathy were prospectively enrolled. All patients underwent CMR with T1 mapping. ECV was calculated incorporating native and post-contrast T1 as well as hematocrit. LV GLS, GCS, and GRS were assessed by feature tracking. Hazard ratios and Kaplan-Meier curves were produced to assess the association between strains and T1 mapping indices with a composite outcome of all-cause mortality and hospitalized heart failure. RESULTS: The study consisted of 259 patients with mixed referring diagnoses of non-ischemic/ischemic cardiomyopathy and 21 normal controls. Decreased GLS, GCS and GRS were associated with increased ECV, increased native T1, and reduced post-contrast T1 in a dose dependent manner when T1 or ECV was in the abnormal range. After a mean follow-up of 31 ± 23 months, 41 events occurred including 37 heart failure admissions and 4 deaths. Kaplan-Meier plots demonstrated that reduced strains were associated with reduced event-free survival predominantly in patients with increased ECV (≥ 28.3%). The worst outcome was among those with both reduced strains and increased ECV. In the multivariable models, increased ECV, reduced post-contrast T1 and reduced strains in all 3 directions remained predictors of outcome risk, respectively. CONCLUSION: Our findings highlight the intrinsic link between altered CMR tissue properties and impaired myocardial mechanical performance and additionally demonstrate improved risk stratification by characterizing tissue property among patients with reduced strain.

Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort.

OBJECTIVE: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts. DESIGN AND METHODS: Longitudinal plasma samples from the treatment-naive control arm of the Short Pulse Anti-Retroviral Therapy at Seroconversion (SPARTAC) primary HIV-1 infection cohort were used in an HIV-1 pseudotype neutralization assay to measure the neutralization breadth, potency and specificity of bnAb responses over time. RESULTS: In the SPARTAC cohort, development of plasma neutralization breadth and potency correlates with duration of HIV infection and high viral loads, and typically takes 3-4 years to arise. bnAb activity was mostly directed to one or two bnAb epitopes per donor and more than 60% of donors with the highest plasma neutralization having bnAbs targeted towards glycan-dependent epitopes. CONCLUSION: This study highlights the SPARTAC cohort as an important resource for more in-depth analysis of bnAb developmental pathways.

Long-term all-cause mortality among asymptomatic individuals with 80th percentile of coronary calcium score based on age and gender in the St. Francis Heart Study.

OBJECTIVES: High coronary artery calcium score (CAC) is a significant risk factor for cardiovascular morbidity and mortality. We investigated the long-term outcome of subjects with elevated CAC. METHODS: We studied 1005 participants of The St. Francis Heart Study who were asymptomatic and apparently healthy and had CAC scores at 80th percentile or higher for age and gender. They were randomized to receive atorvastatin 20 mg daily or placebo for up to 5 years. We used an as-treated study design accounting for cross-overs at the end of the original trial. All-cause mortality risk was assessed using adjusted hazard ratios. RESULTS: Mean age was 59 ± 6 years and 26% (N = 263) were female. After 17 ± 3 years follow-up 176 subjects died. High CAC at baseline was associated with increased mortality risk with adjusted hazard ratio for logarithmic transformed CAC at 1.33 and 95% confidence interval 1.06-1.68. The mortality risk associated with CAC was similar between the group with high-sensitivity CRP ≥2 and <2 mg/dL. Those with a family history of premature coronary artery disease exhibited a higher mortality risk in association with high CAC with an adjusted hazard ratio 1.51 (1.09, 2.09). CONCLUSION: Elevated CAC is an independent risk for long-term all-cause mortality. The screening of CAC score in addition to identifying conventional risk factors can differentiate asymptomatic individuals with and without increased long-term mortality risk.

Trends in Cardiovascular MRI and CT in the U.S. Medicare Population from 2012 to 2017.

PURPOSE: To assess the characteristics and trends of cardiovascular MRI and CT practitioners and practice in the United States. MATERIALS AND METHODS: A retrospective cross-sectional analysis of 2012-2017 Medicare Part B physician payments from the Provider Utilization and Payment Data Physician and Other Supplier Public Use Files (POSPUF) was performed. Characteristics of cardiovascular MRI and CT, including the number of providers and examinations, provider sex and location, and physician reimbursement were analyzed. Variable means, standard deviations, and changes per year were reported and compared. RESULTS: In 2017, 582 physicians provided cardiovascular MRI services in 45 states, a 16.6% increase from 2016 and an 84.8% increase from 2012. A total of 1645 physicians provided cardiovascular CT services in 49 states, a 14.2% increase from 2016 and a 77.3% increase from 2012. Of the providers, 18.0% and 13.3% of cardiovascular MRI and CT providers were women, respectively, similar to providers' respective medical specialties. Only 1.0% of radiologists and 0.2% of cardiologists provided cardiovascular MRI services. A total of 3.2% of radiologists and 0.5% of cardiologists provided cardiovascular CT services. Both cardiovascular MRI use (+75.5%) and cardiovascular CT use (+97.4%) increased markedly over the 6-year study period. CONCLUSION: Although the availability of cardiovascular MRI and CT is increasing, both are used less frequently in comparison with other cardiovascular imaging modalities.See also the commentary by Bierhals in this issue.Supplemental material is available for this article.© RSNA, 2021.