Tributes to Professor Robert Berkley Harper

In 1977, I began teaching at The University of Pittsburgh Law School and in short order one of my closest friends during my tenure there was Professor Robert “Bob” Harper. I wondered when I was hired whether I was selected because I looked strikingly similar to Bob, and perhaps the faculty thought my favoring Professor Harper would make my assimilation into the law school faculty that much easier. Students constantly called me Professor Harper and, indeed, many on the faculty called me Bob for several years; I never bothered to correct them. I thought if they paid that little attention to detail in law school, I would just let them go through life missing some of the finer points their education, and life for that matter, has to offer

Fast Measurements of Flow Through Mitral Regurgitant Orifices With Magnetic Resonance Phase Velocity Mapping

Magnetic-resonance (MR) phase velocity mapping (PVM) shows promise in measuring the mitral regurgitant volume. However, in its conventional nonsegmented form, MR-PVM is slow and impractical for clinical use. The aim of this study was to evaluate the accuracy of rapid, segmented k-spaceMR-PVM in quantifying the mitral regurgitant flow through a control volume (CV) method. Two segmented MR-PVM schemes, one with seven (seg-7) and one with nine (seg-9) lines per segment, were evaluated in acrylic regurgitant mitral valve models under steady and pulsatile flow. A nonsegmented (nonseg) MR-PVM acquisition was also performed for reference. The segmented acquisitions were considerably faster (min) than the nonsegmented (\u3e45 min). The regurgitant flow rates and volumes measured with segmented MR-PVM agreed closely with those measured with nonsegmented MR-PVM (differences 0.05), when the CV was large enough to exclude the region of flow acceleration and aliasing from its boundaries. The regurgitant orifice shape (circular vs. slit-like) and the presence of aortic outflow did not significantly affect the accuracy of the results under both steady and pulsatile flow (p\u3e0.05). This study shows that segmented k-space MR-PVM canaccurately quantify the flow through regurgitant orifices using the CV method and demonstrates great clinical potential

Methodology of a reevaluation of cardiovascular outcomes in the RECORD trial: study design and conduct

Background In 2010, after regulatory review of rosiglitazone licensing, the US Food and Drug Administration (FDA) requested a reevaluation of cardiovascular end points in the RECORD trial.<p></p> Methods Automated screening of the original clinical trial database and manual case report form review were performed to identify all potential cardiovascular and noncardiovascular deaths, and nonfatal myocardial infarction (MI) and stroke events. Search techniques were used to find participants lost to follow-up, and sites were queried for additional source documents. Suspected events underwent blinded adjudication using both original RECORD end point definitions and new FDA end point definitions, before analysis by the Duke Clinical Research Institute.<p></p> Results The reevaluation effort included an additional 328 person-years of follow-up. Automated screening identified 396 suspected deaths, 2,052 suspected MIs, and 468 suspected strokes. Manual review of documents by Duke Clinical Research Institute clinical events classification (CEC) coordinators identified an additional 31 suspected deaths, 49 suspected MIs, and 28 suspected strokes. There were 127 CEC queries issued requesting additional information on suspected deaths; 43 were closed with no site response, 61 were closed with a response that no additional data were available, and additional data were received for 23. Seventy CEC queries were issued requesting additional information for suspected MI and stroke events; 31 were closed with no site response, 20 were closed with a response that no additional data were available, and 19 resulted in additional data.<p></p> Conclusions Comprehensive procedures were used for rigorous event reascertainment and readjudication in a previously completed open-label, global clinical trial. These procedures used in this unique situation were consistent with other common approaches in the field, were enhanced to address the FDA concerns about the original RECORD trial results, and could be considered by clinical trialists designing event readjudication protocols for drug development programs that have been completed.<p></p&gt

Results of a reevaluation of cardiovascular outcomes in the RECORD trial

Background The US Food and Drug Administration (FDA) required a reevaluation of cardiovascular (CV) outcomes in the RECORD trial. This provided an opportunity to assess the implications of event adjudication by 2 groups and quantify the differences as well as to use new FDA end point definitions in development.<p></p> Methods Original data were used to systematically identify all potential deaths, myocardial infarctions (MIs), and strokes. Site investigators were approached for additional source documents and information about participants lost to follow-up. Suspected events were adjudicated using standard procedures, and the results were compared with the original trial outcomes.<p></p> Results Follow-up for mortality was 25,833 person-years, including an additional 328 person-years identified during the reevaluation effort. A total of 184 CV or unknown-cause deaths (88 rosiglitazone, 96 metformin/sulfonylurea), 128 participants with an MI (68 rosiglitazone, 60 metformin/sulfonylurea), and 113 participants with a stroke (50 rosiglitazone, 63 metformin/sulfonylurea) were included. The hazard ratio (HR) for rosiglitazone versus metformin/sulfonylurea for the end point of CV (or unknown cause) death, MI, or stroke was 0.95 (95% CI 0.78-1.17) compared with 0.93 (95% CI 0.74-1.15) for the original RECORD results. Treatment comparisons for MI (HR 1.13, 95% CI 0.80-1.59) and mortality (HR 0.86, 95% CI 0.68-1.08) were also the same compared with the original RECORD results. Sensitivity analyses were also consistent with the original RECORD results. Analyses using the FDA definitions showed similar results.<p></p> Conclusions Only a modest number of additional person-years of follow-up were ascertained from this reevaluation of CV end points in RECORD. Observed HRs and CIs from these analyses using the original RECORD or new FDA end point definitions showed similar treatment effects of rosiglitazone compared with the original RECORD results.<p></p&gt

Sex-specific fundamental and formant frequency patterns in a cross-sectional study

An extensive developmental acoustic study of the speech patterns of children and adults was reported by Lee and colleagues [Lee et al., J. Acoust. Soc. Am. 105, 1455-1468 (1999)]. This paper presents a reexamination of selected fundamental frequency and formant frequency data presented in their report for 10 monophthongs by investigating sex-specific and developmental patterns using two different approaches. The first of these includes the investigation of age- and sex-specific formant frequency patterns in the monophthongs. The second, the investigation of fundamental frequency and formant frequency data using the critical band rate (bark) scale and a number of acoustic-phonetic dimensions of the monophthongs from an age- and sex-specific perspective. These acoustic-phonetic dimensions include: vowel spaces and distances from speaker centroids; frequency differences between the formant frequencies of males and females; vowel openness/closeness and frontness/backness; the degree of vocal effort; and formant frequency ranges. Both approaches reveal both age- and sex-specific development patterns which also appear to be dependent on whether vowels are peripheral or non-peripheral. The developmental emergence of these sex-specific differences are discussed with reference to anatomical, physiological, sociophonetic and culturally determined factors. Some directions for further investigation into the age-linked sex differences in speech across the lifespan are also proposed

Noninvasive Quantification of Fluid Mechanical Energy Losses in the Total Cavopulmonary Connection with Magnetic Resonance Phase Velocity Mapping

A major determinant of the success of surgical vascular modifications, such as the total cavopulmonary connection (TCPC), is the energetic efficiency that is assessed by calculating the mechanical energy loss of blood flow through the new connection. Currently, however, to determine the energy loss, invasive pressure measurements are necessary. Therefore, this study evaluated the feasibility of the viscous dissipation (VD) method, which has the potential to provide the energy loss without the need for invasive pressure measurements. Two experimental phantoms, a U-shaped tube and a glass TCPC, were scanned in a magnetic resonance (MR) imaging scanner and the images were used to construct computational models of both geometries. MR phase velocity mapping (PVM) acquisitions of all three spatial components of the fluid velocity were made in both phantoms and the VD was calculated. VD results from MR PVM experiments were compared with VD results from computational fluid dynamics (CFD) simulations on the image-based computational models. The results showed an overall agreement between MR PVM and CFD. There was a similar ascending tendency in the VD values as the image spatial resolution increased. The most accurate computations of the energy loss were achieved for a CFD grid density that was too high for MR to achieve under current MR system capabilities (in-plane pixel size of less than 0.4 mm). Nevertheless, the agreement between the MR PVM and the CFD VD results under the same resolution settings suggests that the VD method implemented with a clinical imaging modality such as MR has good potential to quantify the energy loss in vascular geometries such as the TCPC

Course-based Science Research Promotes Learning in Diverse Students at Diverse Institutions

Course-based research experiences (CREs) are powerful strategies for spreading learning and improving persistence for all students, both science majors and nonscience majors. Here we address the crucial components of CREs (context, discovery, ownership, iteration, communication, presentation) found across a broad range of such courses at a variety of academic institutions. We also address how the design of a CRE should vary according to the background of student participants; no single CRE format is perfect. We provide a framework for implementing CREs across multiple institutional types and several disciplines throughout the typical four years of undergraduate work, designed to a variety of student backgrounds. Our experiences implementing CREs also provide guidance on overcoming barriers to their implementation

Reliable In-Plane Velocity Measurements With Magnetic Resonance Velocity Imaging

Magnetic resonance (MR) imaging is a well-known diagnostic imaging modality. In addition to its high-quality imaging capabilities, hydrogen-based MR can also provide non-invasively the velocity of water-based fluids in all three spatial directions (through-plane and in-plane) in an image. Many previous studies showed that MR velocity imaging can accurately measure the through-plane velocity. The aim of this study was to evaluate how reliable are the in-plane velocity measurements in an image. The axial velocity of water in horizontal tubes (inner diameter: 14.7–26.2 mm) was measured with segmented (fast) and non-segmented (slow) k-space MR velocity imaging using: (a) an imaging slice placed perpendicular to the tube axis with through-plane velocity-encoding; and (b) an imaging slice placed parallel to the tube axis with in-plane velocity-encoding. The two planes intersected along the vertical tube-centerline. The flow rate was accurately quantified (mean error plane velocity profiles were not significantly different from the through-plane profiles (mean difference =6%, correlation coefficients \u3e0.98). There was no significant difference between the velocity profiles from the segmented and the non-segmented sequences (mean difference 0.95). The results of this study suggest that fast MR velocity imaging can measure the in-plane velocity in an image with reliability

Ultrafast Flow Quantification With Segmented K-Space Magnetic Resonance Phase Velocity Mapping

Magnetic resonance (MR) phase-velocity mapping (PVM) is routinely being used clinically to measure blood flow velocity. Conventional nonsegmented PVM is accurate but relatively slow (3–5 min per measurement). Ultrafast k-space segmented PVM offers much shorter acquisitions (on the order of seconds instead of minutes). The aim of this study was to evaluate the accuracy of segmented PVM in quantifying flow from through-plane velocity measurements. Experiments were performed using four straight tubes (inner diameter of 5.6–26.2 mm), under a variety of steady (1.7–200 ml/s) and pulsatile (6–90 ml/cycle) flow conditions. Two different segmented PVM schemes were tested, one with five k-space lines per segment and one with nine lines per segment. Results showed that both segmented sequences provided very accurate flow quantification (errorsflow conditions, even under turbulent flow conditions. This agreement was confirmed via regression analysis. Further statistical analysis comparing the flow data from the segmented PVM techniques with (i) the data from the nonsegmented technique and (ii) the true flow values showed no significant difference (all p values≫0.05). Preliminary flow measurements in the ascending aorta of two human subjects using the nonsegmented sequence and the segmented sequence with nine lines per segment showed very close agreement. The results of this study suggest that ultrafast PVM has great potential to measure blood velocity and quantify blood flow clinically. © 2002 Biomedical Engineering Society

Ultrafast Flow Quantification With Segmented K-Space Magnetic Resonance Phase Velocity Mapping

Magnetic resonance (MR) phase-velocity mapping (PVM) is routinely being used clinically to measure blood flow velocity. Conventional nonsegmented PVM is accurate but relatively slow (3–5 min per measurement). Ultrafast k-space segmented PVM offers much shorter acquisitions (on the order of seconds instead of minutes). The aim of this study was to evaluate the accuracy of segmented PVM in quantifying flow from through-plane velocity measurements. Experiments were performed using four straight tubes (inner diameter of 5.6–26.2 mm), under a variety of steady (1.7–200 ml/s) and pulsatile (6–90 ml/cycle) flow conditions. Two different segmented PVM schemes were tested, one with five k-space lines per segment and one with nine lines per segment. Results showed that both segmented sequences provided very accurate flow quantification (errorsflow conditions, even under turbulent flow conditions. This agreement was confirmed via regression analysis. Further statistical analysis comparing the flow data from the segmented PVM techniques with (i) the data from the nonsegmented technique and (ii) the true flow values showed no significant difference (all p values≫0.05). Preliminary flow measurements in the ascending aorta of two human subjects using the nonsegmented sequence and the segmented sequence with nine lines per segment showed very close agreement. The results of this study suggest that ultrafast PVM has great potential to measure blood velocity and quantify blood flow clinically. © 2002 Biomedical Engineering Society