Non-invasive evaluation of left ventricular afterload, part 2 : arterial pressure-flow and pressure-volume relations in humans

The mechanical load imposed by the systemic circulation to the left ventricle is an important determinant of normal and abnormal cardiovascular function. Left ventricular afterload is determined by complex time-varying phenomena, which affect pressure and flow patterns generated by the pumping ventricle. Left ventricular afterload is best described in terms of pressure-flow relations, allowing for quantification of various components of load using simplified biomechanical models of the circulation, with great potential for mechanistic understanding of the role of central hemodynamics in cardiovascular disease and the effects of therapeutic interventions. In the second part of this tutorial, we review analytic methods used to characterize left ventricular afterload, including analyses of central arterial pressure-flow relations and windkessel modeling (pressure-volume relations). Conceptual descriptions of various models and methods are emphasized over mathematical ones. Our review is aimed at helping researchers and clinicians obtain and interpret results from analyses of left ventricular afterload in clinical and epidemiological settings

Statistical Methods in Topological Data Analysis for Complex, High-Dimensional Data

The utilization of statistical methods an their applications within the new field of study known as Topological Data Analysis has has tremendous potential for broadening our exploration and understanding of complex, high-dimensional data spaces. This paper provides an introductory overview of the mathematical underpinnings of Topological Data Analysis, the workflow to convert samples of data to topological summary statistics, and some of the statistical methods developed for performing inference on these topological summary statistics. The intention of this non-technical overview is to motivate statisticians who are interested in learning more about the subject.Comment: 15 pages, 7 Figures, 27th Annual Conference on Applied Statistics in Agricultur

SB53-20/21: Resolution Urging UM to Implement a Plastic Bag Ban

SB53-20/21: Resolution Urging UM to Implement a Plastic Bag Ban. This resolution was approved on a 21Y-0N-1A vote during the January 27, 2021 meeting of the Associated Students of the University of Montana (ASUM)

Statistical Methods in Topological Data Analysis for Complex, High-Dimensional Data

The utilization of statistical methods an their applications within the new field of study known as Topological Data Analysis has has tremendous potential for broadening our exploration and understanding of complex, high-dimensional data spaces. This paper provides an introductory overview of the mathematical underpinnings of Topological Data Analysis, the workflow to convert samples of data to topological summary statistics, and some of the statistical methods developed for performing inference on these topological summary statistics. The intention of this non-technical overview is to motivate statisticians who are interested in learning more about the subject

TOPOLOGICAL METHODS FOR THE QUANTIFICATION AND ANALYSIS OF COMPLEX PHENOTYPES

Quantitative Trait Locus (QTL) mapping of complex traits, such as leaf venation or root structures, require the phenotyping and genotyping of large populations. Sufficient genotyping is accomplished with cost effective high-throughput assays, however labor costs often makes sufficient phenotyping prohibitively limited. In order to develop efficient high-throughput phenotyping platforms for complex traits algorithms and methods for quantifying these traits are needed. It is often desirable to study the spatial organization of these phenotypes from the images generated by high-throughput platforms. With the goal of quantifying the traits, many approaches try to identify several core traits useful in describing the phenotypic morphology. This simplification may lose important information about the phenotype. Rather than reducing the structural information, we introduce a novel method, the Persistence Intensity Array, for studying complex traits using tools from the emergent field of Topological Data Analysis. This approach uses the complete geometry of the phenotype and represents it as a simpler summary of the key topological shape features contained in the data. We demonstrate this method\u27s efficacy by through a simulated QTL analysis

Two-week joint mobilization intervention improves self-reported function, range of motion, and dynamic balance in those with chronic ankle instability

We examined the effect of a 2-week anterior-to-posterior ankle joint mobilization intervention on weight-bearing dorsiflexion range of motion (ROM), dynamic balance, and self-reported function in subjects with chronic ankle instability (CAI). In this prospective cohort study, subjects received six Maitland Grade III anterior-to-posterior joint mobilization treatments over 2 weeks. Weightbearing dorsiflexion ROM, the anterior, posteromedial, and posterolateral reach directions of the Star Excursion Balance Test (SEBT), and self-reported function on the Foot and Ankle Ability Measure (FAAM) were assessed 1 week before the intervention (baseline), prior to the first treatment (pre-intervention), 24–48 h following the final treatment (post-intervention), and 1 week later (1-week follow-up) in 12 adults (6 males and 6 females) with CAI. The results indicate that dorsiflexion ROM, reach distance in all directions of the SEBT, and the FAAM improved (p < 0.05 for all) in all measures following the intervention compared to those prior to the intervention. No differences were observed in any assessments between the baseline and pre-intervention measures or between the postintervention and 1-week follow-up measures (p > 0.05). These results indicate that the joint mobilization intervention that targeted posterior talar glide was able to improve measures of function in adults with CAI for at least 1 week

Impact of diabetes mellitus on ventricular structure, arterial stiffness, and pulsatile hemodynamics in heart failure with preserved ejection fraction

Background-Heterogeneity in the underlying processes that contribute to heart failure with preserved ejection fraction (HFpEF) is increasingly recognized. Diabetes mellitus is a frequent comorbidity in HFpEF, but its impact on left ventricular and arterial structure and function in HFpEF is unknown. Methods and Results-Weassessed the impact of diabetesmellitus on left ventricular cellular and interstitial hypertrophy (assessedwith cardiacmagnetic resonance imaging, including T1mapping pregadolinium and postgadolinium administration), arterial stiffness (assessed with arterial tonometry), and pulsatile arterial hemodynamics (assessed with in-office pressure-flow analyses and 24-hour ambulatory monitoring) among 53 subjects with HFpEF (32 diabetic and 21 nondiabetic subjects). Despite few differences in clinical characteristics, diabetic subjects with HFpEF exhibited a markedly greater left ventricular mass index (78.1 [95% CI, 70.4-85.9] g versus 63.6 [95% CI, 55.8-71.3] g; P=0.0093) and indexed extracellular volume (23.6 [95% CI, 21.2-26.1] mL/m(2) versus 16.2 [95% CI, 13.1-19.4] mL/m(2); P=0.0008). Pronounced aortic stiffening was also observed in the diabetic group (carotid-femoral pulse wave velocity, 11.86 [95% CI, 10.4-13.1] m/s versus 8.8 [95% CI, 7.5-10.1] m/s; P=0.0027), with an adverse pulsatile hemodynamic profile characterized by increased oscillatory power (315 [95% CI, 258-373] mWversus 190 [95% CI, 144-236] mW; P=0.0007), aortic characteristic impedance (0.154 [95% CI, 0.124-0.183] mmHg/mL per second versus 0.096 [95% CI, 0.072-0.121] mm Hg/mL per second; P=0.0024), and forward (59.5 [95% CI, 52.8-66.1] mm Hg versus 40.1 [95% CI, 31.6-48.6] mm Hg; P=0.0010) and backward (19.6 [95% CI, 16.2-22.9] mm Hg versus 14.1 [95% CI, 10.9-17.3] mm Hg; P=0.0169) wave amplitude. Abnormal pulsatile hemodynamics were also evident in 24-hour ambulatory monitoring, despite the absence of significant differences in 24-hour systolic blood pressure between the groups. Conclusions-Diabetes mellitus is a key determinant of left ventricular remodeling, arterial stiffness, adverse pulsatile hemodynamics, and ventricular-arterial interactions in HFpEF

Correlates of measured prehypertension and hypertension in Latina women living along the US-Mexico border, 2007-2009.

IntroductionAlthough Latinos have lower hypertension rates than non-Latino whites and African Americans, they have a higher prevalence of undiagnosed and uncontrolled hypertension. Research on predictors of hypertension has mostly focused on intrapersonal factors with no studies assessing the combined influence of intrapersonal, interpersonal, and environmental factors. The purpose of this study was to assess a broad range of correlates including intrapersonal, interpersonal, and environmental factors on measured blood pressure category (nonhypertensive, prehypertensive, and hypertensive) in a sample of Latina women residing in San Diego, California.MethodsThis cross-sectional study used baseline data from the San Diego Prevention Research Center's Familias Sanas y Activas program, a promotora-led physical activity intervention. The sample was 331 Latinas who self-selected into this program. Backward conditional logistic regression analysis was conducted to determine the strongest correlates of measured blood pressure category.ResultsLogistic regression analysis suggested that the strongest correlates of prehypertension were soda consumption (odds ratio [OR] = 1.34, [1.00-1.80], P ≤ .05) and age (OR = 1.03, [1.00-1.05], P ≤ .05). The strongest correlates of hypertension were soda consumption (OR = 1.92, [1.20-3.07], P ≤ .01), age (OR = 1.09, [1.05-1.13], P ≤ .001), and measured body mass index (OR = 1.13, [1.05-1.22], P ≤ .001). All analyses controlled for age and education. No interpersonal or environmental correlates were significantly associated with blood pressure category.ConclusionFuture research should aim to further understand the role of soda consumption on risk for hypertension in this population. Furthermore, interventions aimed at preventing hypertension may want to focus on intrapersonal level factors

Afatinib for the Treatment of \u3cem\u3eEGFR\u3c/em\u3e Mutation-Positive NSCLC: A Review of Clinical Findings

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors represent the standard of care in patients with EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC). The availability of several EGFR tyrosine kinase inhibitors approved for use in the first-line or later settings in NSCLC warrants an in-depth understanding of the pharmacological properties of, and clinical data supporting, these agents. The second-generation, irreversible ErbB-family blocker, afatinib, has been extensively studied in the context of EGFRm+ NSCLC. Results from the LUX-Lung 3 and 6 studies showed that afatinib was more active and better tolerated than chemotherapy in patients with tumors harboring EGFR mutations. Subanalysis of these trials, along with real-world data, indicates that afatinib is active in patients with certain uncommon EGFR mutations (S768I/G719X/L861Q) as well as common mutations (Del19/L858R), and in patients with active brain metastases. In LUX-Lung 7, a head-to-head phase IIb trial, afatinib improved progression-free survival and time-to-treatment failure versus the first-generation reversible EGFR tyrosine kinase inhibitor, gefitinib, albeit with a higher incidence of serious treatment-related adverse events. Nevertheless, afatinib is generally well tolerated, and adverse events are manageable through supportive care and a well-defined tolerability-guided dose adjustment scheme. In this review, we provide a detailed overview of the pharmacology, efficacy, and safety of afatinib, discuss treatment sequencing strategies following emergence of different resistance mechanisms, and shed light on the economic impact of afatinib. We also provide a comparison of afatinib with the available EGFR tyrosine kinase inhibitors and discuss its position within treatment strategies for patients with EGFRm+ NSCLC

Early and late systolic wall stress differentially relate to myocardial contraction and relaxation in middle-aged adults: the Asklepios study

Experimental studies implicate late systolic load as a determinant of impaired left ventricular (LV) relaxation. We aimed to assess the relationship between the myocardial loading sequence and left ventricular (LV) contraction and relaxation. Time-resolved central pressure and time-resolved LV geometry were measured with carotid tonometry and speckle-tracking echocardiography, respectively, for computation of time-resolved ejection-phase myocardial wall stress (EP-MWS) among 1,214 middle-aged adults without manifest cardiovascular disease from the general population. Early diastolic annular velocity, systolic annular velocities were measured with tissue Doppler imaging and segmentaveraged longitudinal strain was measured with speckle-tracking echocardiography. After adjustment for age, gender and potential confounders, late EP-MWS was negatively associated with early diastolic mitral annular velocity (e', standardized β=-0.25; P<0.0001) and mitral inflow propagation velocity (Vpe, standardized β=-0.13; P=0.02). In contrast, early EP-MWS was positively associated with e' (standardized β=0.18; P<0.0001) and Vpe (standardized β=0.22; P<0.0001). A higher late EP-MWS predicted a lower systolic mitral annular velocity (S', standardized β=-0.31; P<0.0001) and lesser myocardial longitudinal strain (standardized β=0.32; P<0.0001), whereas a higher early EP-MWS was associated with a higher S' (standardized β=0.16; P=0.002) and greater longitudinal strain (standardized β=-0.24; P=0.002). The loading sequence remained independently associated with e' after adjustment for S' or systolic longitudinal strain. In the context of available experimental data, our findings support the role of the myocardial loading sequence as a determinant of LV systolic and diastolic function. A loading sequence characterized by prominent late systolic wall stress was associated with lower longitudinal systolic function and diastolic relaxation