Biomedical doctoral students' research practices when facing dilemmas: two vignette-based randomized control trials.

Our aim was to describe the research practices of doctoral students facing a dilemma to research integrity and to assess the impact of inappropriate research environments, i.e. exposure to (a) a post-doctoral researcher who committed a Detrimental Research Practice (DRP) in a similar situation and (b) a supervisor who did not oppose the DRP. We conducted two 2-arm, parallel-group randomized controlled trials. We created 10 vignettes describing a realistic dilemma with two alternative courses of action (good practice versus DRP). 630 PhD students were randomized through an online system to a vignette (a) with (n = 151) or without (n = 164) exposure to a post-doctoral researcher; (b) with (n = 155) or without (n = 160) exposure to a supervisor. The primary outcome was a score from - 5 to + 5, where positive scores indicated the choice of DRP and negative scores indicated good practice. Overall, 37% of unexposed participants chose to commit DRP with important variation across vignettes (minimum 10%; maximum 66%). The mean difference [95%CI] was 0.17 [- 0.65 to 0.99;], p = 0.65 when exposed to the post-doctoral researcher, and 0.79 [- 0.38; 1.94], p = 0.16, when exposed to the supervisor. In conclusion, we did not find evidence of an impact of postdoctoral researchers and supervisors on student research practices.Trial registration: NCT04263805, NCT04263506 (registration date 11 February 2020).

Stability of elliptical cylinders in two-dimensional channel flow.

The flow around rigid cylinders of elliptical cross section placed transverse to Poiseuille flow between parallel plates was simulated to investigate issues related to the tumbling of red blood cells and other particles of moderate aspect ratio in the similar flow in a Field Flow Fractionation (FFF) channel. The torque and transverse force on the cylinder were calculated with the cylinder freely translating, but prevented from rotating, in the flow. The aspect ratios (long axis to short axis) of the elliptical cylinders were 2, 3, 4, and 5. The cylinder was placed transversely at locations of y0/H = 0.1, 0.2, 0.3, and 0.4, where y0 is the distance from the bottom of the channel and H is the height of the channel, and the orientation of the cylinder was varied from 0 to 10 deg with respect to the axis of the channel for a channel Reynolds number of 20. The results showed that equilibrium orientations (indicated by a zero net torque on the cylinder) were possible for high-aspect-ratio cylinders at transverse locations y0/H < 0.2. Otherwise, the net torque on the cylinder was positive, indicating that the cylinder would rotate. For cylinders with a stable orientation, however, a transverse lift forced existed up to about y0/H = 0.25. Thus, a cylinder of neutral or low buoyancy might be lifted with a stable orientation from an initial position near the wall until it reached y0/H < 0.2, whereupon it would begin to tumble or oscillate. The dependence of lift and torque on cylinder orientation suggested that neutral or low-buoyancy cylinders may oscillate in both transverse location and angular velocity. Cylinders more dense than the carrier fluid could be in equilibrium both in terms of orientation and transverse location if their sedimentation force matched their lift force for a location y0/H < 0.2.

Aortic input impedance in infants and children.

Flow and pressure measurements were performed in the ascending aortas of six pediatric patients ranging in age from 1 to 4 yr and in weight from 7.2 to 16.4 kg. From these measurements, input impedance was calculated. It was found that total vascular resistance decreased with increasing patient weight and was approximately one to three times higher than those of adults. Conductance per unit weight was relatively constant but was approximately three times higher than for adults. Strong inertial character was observed in the impedance of four of the six patients. Among a three-element and two four-element lumped-parameter models, the model with characteristic aortic resistor (R(c)) and inertance in series followed by parallel peripheral resistor (R(p)) and compliance fitted the data best. R(p) decreased with increasing patient weight and was one to three times higher than in adults, and R(c) decreased with increasing patient weight and was 2 to 15 times higher. The R(p)-to-R(c) ratio differed significantly between infants and children vs. adults. The results suggested that R(p) developed more rapidly with patient weight than did R(c). Compliance values increased with increasing patient weight and were 3 to 16 times lower than adult values.

Development of a hydraulic model of the human systemic circulation.

Physical and numeric models of the human circulation are constructed for a number of objectives, including studies and training in physiologic control, interpretation of clinical observations, and testing of prosthetic cardiovascular devices. For many of these purposes it is important to quantitatively validate the dynamic response of the models in terms of the input impedance (Z = oscillatory pressure/oscillatory flow). To address this need, the authors developed an improved physical model. Using a computer study, the authors first identified the configuration of lumped parameter elements in a model of the systemic circulation; the result was a good match with human aortic input impedance with a minimum number of elements. Design, construction, and testing of a hydraulic model analogous to the computer model followed. Numeric results showed that a three element model with two resistors and one compliance produced reasonable matching without undue complication. The subsequent analogous hydraulic model included adjustable resistors incorporating a sliding plate to vary the flow area through a porous material and an adjustable compliance consisting of a variable-volume air chamber. The response of the hydraulic model compared favorably with other circulation models.

Feedback control of mean aortic pressure in a dynamic model of the cardiovascular system.

Orbital measurements of the cardiac function of Space Shuttle crew members have shown an initial increase in cardiac stroke volume upon entry into weightlessness, followed by a gradual reduction in stroke volume to a level approximately 15% less than preflight values. In an effort to explain this response, it was hypothesized that gravity plays a role in cardiac filling. A mock circulatory system was designed to investigate this effect. Preliminary studies carried out with this system on the NASA KC-135 aircraft, which provides brief periods of weightlessness, showed a strong correlation between cardiac filling, stroke volume, and the presence or absence of gravity. The need for extended periods of high quality zero gravity was identified to verify this observation. To accomplish this, the aircraft version of the experiment was reduced in size and fully automated for eventual integration into a Get Away Special canister to conduct an orbital version of the experiment. This article describes the automated system, as well as the development and implementation of a control algorithm for the servoregulation of the mean aortic pressure in the orbital experiment. Three nonlinearities that influence the ability of the apparatus to regulate to a mean aortic pressure of 95 mm Hg were identified and minimized. In preparation for a Space Shuttle flight, the successful function of the servoregulatory scheme was demonstrated during ground tests and additional test flights aboard the KC-135. The control algorithm was successful in carrying out the experimental protocol, including regulation of mean aortic pressure. The algorithm could also be used for the automated operation of long-term tests of circulatory support systems, which may require a scheduled cycling of the pumping conditions on a daily basis.

Finite element analysis of the lift on a slightly deformable and freely rotating and translating cylinder in two-dimensional channel flow.

Motivated by the lateral migration phenomena of fresh and glutaraldehyde-fixed red blood cells in a field flow fractionation (FFF) separation system, we studied the transverse hydrodynamic lift on a slightly flexible cylinder in a two-dimensional channel flow. The finite element method was used to analyze the flow field with the cylinder at different transverse locations in the channel. The shape of the cylinder was determined by the pressure on the surface of the cylinder from the flow field solution and by the internal elastic stress. The cylinder deformation and the flow field were solved simultaneously. The transverse lift exerted on the cylinder was then calculated. The axial and angular speed of the cylinder were iterated such that the drag and torque on the cylinder were nulled to represent a freely translating and rotating state. The results showed that the transverse lift on a deformable cylinder increased greatly and the equilibrium position moved closer to the center of the channel compared to a rigid cylinder. Also, with the same elastic modulus but a higher flow rate, a larger deformation and higher equilibrium location were found. The maximum deformation of the cylinder occurred when the cylinder was closest to the wall where a larger shear rate existed. The numerical results and experimental studies are discussed.

Influence of gravity on cardiac performance.

Results obtained by the investigators in ground-based experiments and in two parabolic flight series of tests aboard the NASA KC-135 aircraft with a hydraulic simulator of the human systemic circulation have confirmed that a simple lack of hydrostatic pressure within an artificial ventricle causes a decrease in stroke volume of 20%-50%. A corresponding drop in stroke volume (SV) and cardiac output (CO) was observed over a range of atrial pressures (AP), representing a rightward shift of the classic CO versus AP cardiac function curve. These results are in agreement with echocardiographic experiments performed on space shuttle flights, where an average decrease in SV of 15% was measured following a three-day period of adaptation to weightlessness. The similarity of behavior of the hydraulic model to the human system suggests that the simple physical effects of the lack of hydrostatic pressure may be an important mechanism for the observed changes in cardiac performance in astronauts during the weightlessness of space flight.

Scaling of hemolysis in needles and catheters.

Hemolysis in clinical blood samples leads to inaccurate assay results and often to the need for repeated blood draws. In vitro experiments were conducted to determine the influence on hemolysis in phlebotomy needles and catheters of pressure difference, cannula diameter, and cannula material. Fresh blood from five human volunteers was forced from a syringe inside a pressurized chamber through 14, 18, and 22 gauge 304 stainless steel needles and polyurethane and Teflon catheters, all 40 mm long. Hemolysis was measured in the samples by a spectrophotometer. It was found that hemolysis increased with increases in pressure difference and cannula diameter and no consistent trend could be identified with regard to cannula material. The pressure differences required for significant hemolysis were above those typical of clinical venipuncture blood draws. While there was substantial variability among individuals, the hemolysis values scaled with exponent S = (t/t0)[(tau/tau0)-1]2, where t is the characteristic duration of shear, t0 is a time constant, tau is the wall shear stress, and tau0 is the wall shear stress threshold below which no hemolysis occurs. A hemolysis threshold including both time and shear stress was also defined for S = constant. The threshold implies that a threshold shear stress exists below which erythrocytes are not damaged for any length of exposure time, but that red cells may be damaged by an arbitrarily short period of exposure to sufficiently large shear stress.

Compact compliance chamber design for the study of cardiac performance in microgravity.

A need was identified for a Mock Circulation System (MCS) of small size and weight that could function in a microgravity environment for the investigation of cardiovascular response to the weightlessness of space flight. Part of the MCS development involved the redesign of the compliance chamber from a Penn State MCS using a coil spring instead of the leaf spring system employed in the Penn State system. The new compliance chambers achieve a weight reduction of 47% and a volume reduction of 64% over the original Penn State design. Testing showed the coil spring compliance chambers retained physiologic characteristics and adjustability by using coil springs of various stiffness, and functioned equivalently to the original Penn State design.

A blood analog for laser-induced photochemical anemometry.

A transparent viscoelastic blood analog fluid was developed for use with Laser-Induced Photochemical Anemometry. To provide solubility of the photochemical tracer, 1', 3', 3'-trimethyl-6-nitroindoline-2-benzopyran (TNSB dye, Kodak Chemicals), the analog solvent needed to be nonpolar, thus currently available aqueous blood analogs were not suitable. An analog consisting of 0.04% ethylhydroxyethylcellulose dissolved in gamma-butyrolactone produced a pseudoplastic steady shear response with low elasticity in unsteady shear, while being compatible with the photochemical tracer.

The effect of blood viscoelasticity on pulsatile flow in stationary and axially moving tubes.

An analytical solution for pulsatile flow of a generalized Maxwell fluid in straight rigid tubes, with and without axial vessel motion, has been used to calculate the effect of blood viscoelasticity on velocity profiles and shear stress in flows representative of those in the large arteries. Measured bulk flow rate Q waveforms were used as starting points in the calculations for the aorta and femoral arteries, from which axial pressure gradient delta P waves were derived that would reproduce the starting Q waves for viscoelastic flow. The delta P waves were then used to calculate velocity profiles for both viscoelastic and purely viscous flow. For the coronary artery, published delta P and axial vessel acceleration waveforms were used in a similar procedure to determine the separate and combined influences of viscoelasticity and vessel motion. Differences in local velocities, comparing viscous flow to viscoelastic flow, were in all cases less than about 2% of the peak local velocity. Differences in peak wall shear stress were less than about 3%. In the coronary artery, wall shear stress differences between viscous and viscoelastic flow were small, regardless of whether axial vessel motion was included. The shape of the wall shear stress waveform and its difference, however, changed dramatically between the stationary and moving vessel cases. The peaks in wall shear stress difference corresponded with large temporal gradients in the combined driving force for the flow.

An orbiting scroll blood pump without valves or rotating seals.

Valves in blood pumps are expensive and provide modes of failure. Rotating seals offer sites of thrombus formation and infection. In this study, a prototype pump incorporating no valves or rotating seals was constructed and tested. In this device, fluid is pumped by the orbital action of a spiral shaped scroll relative to an identical stationary scroll whose starting axis is rotated 180 degrees with respect to the orbiting scroll. The two scrolls, which are machined integral with scroll plates, form pockets that are filled from the outside and then ejected in the center as the orbiting scroll completes each cycle. The orbiting scroll is driven by a crank mechanism connected to a motor. Fluid is contained in the space around the scrolls by a flexible collar and does not contact the driving mechanism. The prototype pump is approximately 7.6 cm in diameter and 2.5 cm thick and has an orbiting radius of 5.1 mm. The output of the pump was very sensitive to the clearance between the scroll tip and the base of the opposite scroll plate. For a clearance of 51 microns, pressure differences as high as 400 mmHg and flows as high as 7.7 l/min (of water) were produced at 260 rpm. At 450 rpm with a 330 microns clearance, pressure differences as high as 185 mmHg and flows as high as 7.3 l/min resulted. The relationships between pressure difference and flow were very linear in all cases. Volumetric efficiency was as high as 70% and increased with speed.

Shear-augmented dispersion in non-Newtonian fluids.

The rate of spread of a passive species is modified by the superposition of a velocity gradient on the concentration field. Taylor (18) solved for the rate of axial dispersion in fully developed steady Newtonian flow in a straight pipe under the conditions that the dispersion be relatively steady and that longitudinal transport be controlled by convection rather than diffusion. He found that the resulting effective axial diffusivity was proportional to the square of the Peclet number Pec and inversely proportional to the molecular diffusivity. This article shows that under similar conditions in Casson and power law fluids, both simplified models for blood, and in Bingham fluids the same proportionalities are found. Solutions are presented for fully developed steady flow in a straight tube and between flat plates. The proportionality factor, however, is dependent upon the specific rheology of the fluid. For Bingham and Casson fluids, the controlling parameter is the radius of the constant-velocity core in which the shear stress does not exceed the yield stress of the fluid. For a core radius of one-tenth the radius of the tube, the effective axial diffusivity in Casson fluids is reduced to approximately 0.78 times that in a Newtonian fluid at the same flow. Using average flow conditions, it is found that the core radius/tube radius ratio is 0 (10(-2)) to 0 (10(-1)) in canine arteries and veins. Even at these small values, the effective diffusivity is diminished by 5% to 18%. For power law fluids, Pec2 dependence is again found, but with a proportionality constant dependent upon the power law exponent n.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of viscosity and pressure on prosthetic valve regurgitation.

Blood viscosity varies during the course of artificial heart implants and is affected by pathological conditions. To gauge the potential effect of changing viscosity on valve performance, leakage rates were measured across a closed Medtronic-Hall valve with water, water/glycerol and fresh whole bovine blood for aortic and pulmonary pressure ranges. As might be expected from the low Reynolds numbers (< 140), losses across the valve were found to be primarily viscous. For the two Newtonian fluids, leakage was slightly less than linearly proportional to pressure. This is comparable with empirical data for orifice flow, which predicts three fifths power dependence on pressure. For blood, however, the greater than linear dependence on pressure found suggests that the pseudoplasticity (shear-thinning behavior) of blood is important. These data provide evidence that the viscous and non-Newtonian properties of blood must be taken into account in modelling prosthetic valve performance and may affect the test methods and flow regulation strategies for prosthetic blood pumps.

Sensitivity of the artificial heart to changes in vascular resistance.

For conditions near those for normal operation, the cardiac output of the healthy natural heart is inherently sensitive to systemic venous resistance but is relatively insensitive to arterial resistance. A mathematical comparison was undertaken to discover the differences in the sensitivity of two configurations of artificial hearts to these resistances. It was found that one design incorporating independently pumping ventricles can be tailored to passively mimic the sensitivity of the natural heart. However, the other design with volumetrically coupled pumping is incapable of exhibiting similar sensitivity through passive means.