Frank Crawford, UM Football Coach, 1892

[cropped from 1892 Michigan baseball team photo]

Influences of accommodation and myopia on the foveal Stiles-Crawford effect

We determined the foveal Stiles-Crawford effect (SCE) as a function of up to 8D accommodation stimulus in six young emmetropes and six young myopes using a psychophysical two-channel Maxwellian system in which the threshold luminance increment of a 1 mm spot entering through variable positions in the pupil was determined against a background formed by a 4 mm spot entering the pupil centrally. The SCE became steeper in both groups with increasing accommodation stimulus, but with no systematic shift of the peak. Combining the data of both groups gave significant increases in directionality of 15-20% in horizontal and vertical pupil meridians with 6D of accommodation. However, additional experiments indicated that much of this was an artefact of higher order aberrations and accommodative lag. Thus, there appears to be little changes in orientation or directionality in the SCE with accommodation stimulus levels up to 6 D, but it is possible that changes may occur at very high accommodation levels

Variation of the Stiles-Crawford effect with accommodation and myopia

Background: Mechanical forces either due to accommodation or myopia may stretch the retina and/or cause shear between the retina and choroid. This can be investigated by making use of the Stiles-Crawford effect (SCE), which is the phenomenon of light changing in apparent brightness as it enters through different positions in the pupil. The SCE can be measured by psychophysical and objective techniques, with the SCE parameters being directionality (rate of change across the pupil), and orientation (the location of peak sensitivity in the pupil). Aims: 1. To study the changes in foveal SCE with accommodation in emmetropes and myopes using a subjective (psychophysical) technique. 2. To develop and evaluate a quick objective technique of measuring the SCE using the multifocal electroretinogram. Methods: The SCE was measured in 6 young emmetropes and 6 young myopes for up to 8 D accommodation stimulus with a psychophysical technique and its variants. An objective technique using the multifocal electroretinogram was developed and evaluated with 5 emmetropes. Results: Using the psychophysical technique, the SCE directionality increased by similar amounts in both emmetropes and myopes as accommodation increased, with an increase of 15-20% with 6 D of accommodation. However, there were no significant orientation changes. Additional measurements showed that most of the change in the directionality was probably an artefact of optical factors such as higher-order aberrations and accommodative lag rather a true effect of accommodation. The multifocal technique demonstrated the presence of the SCE, but results were noisy and too variable to detect any changes in SCE directionality or orientation with accommodation. Conclusion: There is little true change in the SCE with accommodation responses up to 6 D in either emmetropes or myopes, although it is possible that substantial changes might occur at very high accommodation levels. The objective technique using the multifocal electroretinogram was quicker and less demanding for the subjects than the psychophysical technique, but as implemented in this thesis, it is not a reliable method of measuring the SCE.

Frank and Stein : from research scientist to creative writer (a screenplay and exegesis)

The screenplay, “Perfect Blood” (Frank and Stein), is the first two-hour episode of a two-part television miniseries Frank and Stein. This creative work is a science fiction story that speculates on the future of Western nations in a world where petroleum is scarce. A major theme that has been explored in the miniseries is the tension between the advantages and dangers of scientific progress without regard to human consequences. “Perfect Blood” (Frank and Stein) was written as part of my personal creative journey, which has been the transformation from research scientist to creative writer. In the exegetical component of this thesis, I propose that a key challenge for any scientist writing science fiction is the shift from conducting empirical research in a laboratory-based situation to engaging in creative practice research. During my personal creative journey, I found that a predominant difficulty in conducting research within a creative practice-led paradigm was unleashing my creativity and personal viewpoint, practices that are frowned upon in scientific research. The aim of the exegesis is to demonstrate that the transformative process from science to art is not neat and well-structured. My personal creative journey was fraught with many ‘wrong’ turns. However, after reflecting on the experience, I realise that every varied piece of research that I undertook allowed me to progress to the next stage, the next draft of Frank and Stein. And via the disorder of the creative process, a screenplay finally emerged that was both structured and creative, which are equally essential elements in screenwriting.

Replication of the Frank-Starling response in a Mock Circulation loop

Mock circulation loops (MCLs) are used to evaluate cardiovascular devices prior to in-vivo trials; however they lack the vital autoregulatory responses that occur in humans. This study aimed to develop and implement a left and right ventricular Frank-Starling response in a MCL. A proportional controller based on ventricular end diastolic volume was used to control the driving pressure of the MCL’s pneumatically operated ventricles. Ventricular pressure-volume loops and end systolic pressure-volume relationships were produced for a variety of healthy and pathological conditions and compared with human data to validate the simulated Frank-Starling response. The non-linear Frank-Starling response produced in this study successfully altered left and right ventricular contractility with changing preload and was validated with previously reported data. This improvement to an already detailed MCL has resulted in a test rig capable of further refining cardiovascular devices and reducing the number of in-vivo trials.

Frank-starling control of a left ventricular assist device

A physiological control system was developed for a rotary left ventricular assist device (LVAD) in which the target pump flow rate (LVADQ) was set as a function of left atrial pressure (LAP), mimicking the Frank-Starling mechanism. The control strategy was implemented using linear PID control and was evaluated in a pulsatile mock circulation loop using a prototyped centrifugal pump by varying pulmonary vascular resistance to alter venous return. The control strategy automatically varied pump speed (2460 to 1740 to 2700 RPM) in response to a decrease and subsequent increase in venous return. In contrast, a fixed-speed pump caused a simulated ventricular suction event during low venous return and higher ventricular volumes during high venous return. The preload sensitivity was increased from 0.011 L/min/mmHg in fixed speed mode to 0.47L/min/mmHg, a value similar to that of the native healthy heart. The sensitivity varied automatically to maintain the LAP and LVADQ within a predefined zone. This control strategy requires the implantation of a pressure sensor in the left atrium and a flow sensor around the outflow cannula of the LVAD. However, appropriate pressure sensor technology is not yet commercially available and so an alternative measure of preload such as pulsatility of pump signals should be investigated.

Ilse Goldschmidt nee Molling with her sons Ernest and Frank Goldschhmidt on her 80th birthday; Laguna Hills, California.

Left to Right: Ernest Goldschmidt, Ilse Goldschmidt born Molling, and Frank Goldschmidt. The picture was taken on the occasion of Ilse's 80th birthday party 22 Dec 1989 Laguna Hills, CA.

Ilse Goldschmidt nee Molling with her sons Ernest and Frank Goldschhmidt on her 80th birthday; Laguna Hills, California.

Left to Right: Ernest Goldschmidt, Ilse Goldschmidt born Molling, and Frank Goldschmidt. The picture was taken on the occasion of Ilse's 80th birthday party 22 Dec 1989 Laguna Hills, CA.

Outdoor group portrait of Marga Abel, Franzche Wolf, Miss Mahler, Margot Frank and Else Hirschfeld; Bad Kissingen Portraits Groups Women

Handwritten caption: Wir tragen nur Bemberg-Seidenstruempfe! (We wear only Bemberg silk stockings!)

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Ilse Goldschmidt nee Molling with her sons Ernest and Frank Goldschhmidt on her 80th birthday; Laguna Hills, California.

Left to Right: Ernest Goldschmidt, Ilse Goldschmidt born Molling, and Frank Goldschmidt. The picture was taken on the occasion of Ilse's 80th birthday party 22 Dec 1989 Laguna Hills, CA.

Ilse Goldschmidt nee Molling with her sons Ernest and Frank Goldschhmidt on her 80th birthday; Laguna Hills, California.

Left to Right: Ernest Goldschmidt, Ilse Goldschmidt born Molling, and Frank Goldschmidt. The picture was taken on the occasion of Ilse's 80th birthday party 22 Dec 1989 Laguna Hills, CA.