Individualized Structure–Function Mapping for Glaucoma: Practical Constraints on Map Resolution for Clinical and Research Applications

yesPurpose: We have developed customized maps that relate visual field and optic nerve head (ONH) regions according to individual anatomy. In this study, we aimed to determine feasible map resolution for research use, and to make a principled recommendation of sector size for clinical applications. Methods: Measurement variability in fovea–ONH distance and angle was estimated from 10 repeat OCT scans of 10 healthy people. Errors in estimating axial length from refractive error were determined from published data. Structure–function maps were generated, and customized to varied clinically-plausible anatomical parameters. For each parameter set (n = 210), 200 maps were generated by sampling from measurement/estimation error distributions. Mapped 1° sectors at each visual field location from each parameter set were normalized to difference from their mean. Variation (90% ranges) in normalized mapped sectors represents the precision of individualized maps. Results: Standard deviations of repeated measures of fovea–ONH distance and angle were 61 μm and 0.97° (coefficients of variation 1.3% and 12.0%, respectively). Neither measure varied systematically with mean (Spearmans's ρ = 0.26, P = 0.47 for distance, ρ = −0.31, P = 0.39 for angle). Variation (90% ranges) in normalized mapped sectors varied across the visual field and ranged from 3° to 18° when axial length was measured accurately, and from 6° to 32° when axial length was estimated from refractive error. Conclusions: The 90% ranges represent the minimum feasible ONH sector size at each visual field location. For clinical use an easily interpretable scheme of 30° sectors is suggested

Structure–Function Mapping: Variability and Conviction in Tracing Retinal Nerve Fiber Bundles and Comparison to a Computational Model

yesPurpose: We evaluated variability and conviction in tracing paths of retinal nerve fiber bundles (RNFBs) in retinal images, and compared traced paths to a computational model that produces anatomically-customized structure–function maps. Methods: Ten retinal images were overlaid with 24-2 visual field locations. Eight clinicians and 6 naïve observers traced RNFBs from each location to the optic nerve head (ONH), recording their best estimate and certain range of insertion. Three clinicians and 2 naïve observers traced RNFBs in 3 images, 3 times, 7 to 19 days apart. The model predicted 10° ONH sectors relating to each location. Variability and repeatability in best estimates, certain range width, and differences between best estimates and model-predictions were evaluated. Results: Median between-observer variability in best estimates was 27° (interquartile range [IQR] 20°–38°) for clinicians and 33° (IQR 22°–50°) for naïve observers. Median certain range width was 30° (IQR 14°–45°) for clinicians and 75° (IQR 45°–180°) for naïve observers. Median repeatability was 10° (IQR 5°–20°) for clinicians and 15° (IQR 10°–29°) for naïve observers. All measures were worse further from the ONH. Systematic differences between model predictions and best estimates were negligible; median absolute differences were 17° (IQR 9°–30°) for clinicians and 20° (IQR 10°–36°) for naïve observers. Larger departures from the model coincided with greater variability in tracing. Conclusions: Concordance between the model and RNFB tracing was good, and greatest where tracing variability was lowest. When RNFB tracing is used for structure–function mapping, variability should be considered

Effects of glaucoma on detection and discrimination of image blur

YesBlur is one of the most commonly reported visual symptoms of glaucoma, but it is not directly measured by current clinical tests. We aimed to investigate the effects of glaucoma on detection and discrimination of image blur. People with glaucoma, separated into two groups with (n=15) or without (n=17) central visual field defects measured by 10-2 perimetry, and an age-similar control group (n=18) participated. First, we measured contrast detection thresholds centrally using a 2-interval forced choice procedure. We then measured blur detection and discrimination thresholds for the same stimuli (reference blurs 0, 1 arcmin respectively) using a 2-alternative forced choice procedure under two contrast conditions; 4x individual detection threshold for the low contrast condition, 95% contrast for the high contrast condition. The stimulus was a horizontal edge bisecting a hard-edged circle of 4.5° diameter. Data were analysed by linear mixed modelling. Contrast detection thresholds for the glaucoma group with central visual field defects were raised by 0.014 ± 0.004 (mean ± SE, Michelson units) (p=0.002) and by 0.011 ± 0.004 (p=0.03) relative to control and glaucoma without central visual field defect groups respectively. Blur detection and discrimination thresholds were similar between groups, with small elevations in blur detection thresholds in the glaucoma groups not reaching statistical significance (detection p=0.29, discrimination p=0.91). The lower contrast level increased thresholds from the higher contrast level by 1.30 ± 0.10 arcmin (p<0.001) and 1.05 ± 0.096 arcmin (p<0.001) for blur detection and discrimination thresholds respectively. Early-moderate glaucoma resulted in only minimal elevations of blur detection thresholds that did not reach statistical significance in this study. Despite the prevalence of blur as a visual symptom of glaucoma, psychophysical measurements of blur detection or discrimination may not be good candidates for development as clinical tests for glaucomaCollege of Optometrists PhD scholarshi

Suprathreshold Approaches to Mapping the Visual Field in Advanced Glaucoma

YesMeasuring the spatial extent of defects may be advantageous in advanced glaucoma where conventional perimetric sensitivity measurements are unreliable. We test whether suprathreshold tests on a higher density grid can more efficiently map advanced visual field loss. Data from 97 patients with mean deviationSupported by a College of Optometrists Research Fellowship (to JD)

Enhanced structure-function relationship in glaucoma with an anatomically and geometrically accurate neuroretinal rim measurement

yesPurpose: To evaluate the structure–function relationship between disc margin–based rim area (DM-RA) obtained with confocal scanning laser tomography (CSLT), Bruch's membrane opening–based horizontal rim width (BMO-HRW), minimum rim width (BMO-MRW), peripapillary retinal nerve fiber layer thickness (RNFLT) obtained with spectral-domain optical coherence tomography (SD-OCT), and visual field sensitivity. Methods: We examined 151 glaucoma patients with CSLT, SD-OCT, and standard automated perimetry on the same day. Optic nerve head (ONH) and RNFL with SD-OCT were acquired relative to a fixed coordinate system (acquired image frame [AIF]) and to the eye-specific fovea-BMO center (FoBMO) axis. Visual field locations were mapped to ONH and RNFL sectors with fixed Garway-Heath (VFGH) and patient-specific (VFPS) maps customized for various biometric parameters. Results: Globally and sectorally, the structure–function relationships between DM-RA and VFGH, BMO-HRWAIF and VFGH, and BMO-HRWFoBMO and VFPS were equally weak. The R2 for the relationship between DM-RA and VFGH ranged from 0.1% (inferonasal) to 11% (superotemporal) whereas that between BMO-HRWAIF and VFGH ranged from 0.1% (nasal) to 10% (superotemporal). Relatively stronger global and sectoral structure–function relationships with BMO-MRWAIF and with BMO-MRWFoBMO were obtained. The R2 between BMO-MRWAIF and VFGH ranged from 5% (nasal) to 30% (superotemporal), whereas that between BMO-MRWFoBMO and VFPS ranged from 5% (nasal) to 25% (inferotemporal). The structure–function relationship with RNFLT was not significantly different from that with BMO-MRW, regardless of image acquisition method. Conclusions: The structure–function relationship was enhanced with BMO-MRW compared with the other neuroretinal rim measurements, due mainly to its geometrically accurate properties

Effects of criterion bias on perimetric sensitivity and response variability in glaucoma

YesThe purpose of this study was to isolate and quantify the effects of observer response criterion on perimetric sensitivity, response variability, and maximum response probability. Twelve people with glaucoma were tested at three locations in the visual field (age = 47-77 years, mean deviation = -0.61 to -14.54 dB, test location Humphrey field analyzer [HFA] sensitivities = 1 to 30 dB). Frequency of seeing (FoS) curves were measured using a method of constant stimuli with two response paradigms: a "yes-no" paradigm similar to static automated perimetry and a criterion-free two interval forced choice (2IFC) paradigm. Comparison measures of sensitivity, maximum response probability, and response variability were derived from the fitted FoS curves. Sensitivity differences between the tasks varied widely (range = -11.3 dB to 21.6 dB) and did not correlate with visual field sensitivity nor whether the visual field location was in an area of steep sensitivity gradient within the visual field. Due to the wide variation in differences between the methods, there was no significant difference in mean sensitivity between the 2IFC task relative to the yes-no task, but a trend for higher sensitivity (mean = 1.9 dB, SD = 6.0 dB, P = 0.11). Response variability and maximum response probability did not differ between the tasks (P > 0.99 and 0.95, respectively). Perimetric sensitivity estimates are demonstrably altered by observer response criterion but the effect varies widely and unpredictably, even within a single test. Response bias should be considered a factor in perimetric test variability and when comparing sensitivities to nonperimetric data. The effect of response criterion on perimetric response variability varies widely and unpredictably, even within a single test.Supported by ARC LP130100055; ARC LP150100815 (AT and AMM), College of Optometrists Research Fellowship (JD)

An integrated and coordinated approach to preventing recurrent coronary heart disease events in Australia: Policy statement from the Australian Cardiovascular Health and Rehabilitation Association

• Implementing existing knowledge about cardiac rehabilitation (CR) and heart failure management could markedly reduce mortality after acute coronary syndromes and revascularisation therapy. • Contemporary CR and secondary prevention programs are cost-effective, safe and beneficial for patients of all ages, leading to improved survival, fewer revascularisation procedures and reduced rehospitalisation. • Despite the proven benefits attributed to these secondary prevention interventions, they are not well attended by patients. • Modern programs must be flexible, culturally safe, multifaceted and integrated with the patient's primary health care provider to achieve optimal and sustainable benefits for most patients

Differences between patients with ventricular tachycardia and ventricular fibrillation as assessed by signal-averaged electrocardiogram, radionuclide ventriculography and cardiac mapping

AbstractThis study examined 65 patients with ventricular tachycardia or fibrillation late after myocardial infarction to determine whether they differed with respect to duration of ventricular activation in sinus rhythm and left ventricular ejection fraction. Patients with spontaneous ventricular tachycardia had a longer ventricular activation time in sinus rhythm than did patients with spontaneous ventricular fibrillation. This difference was detected with the signal-averaged electrocardiogram (ECG) (tachycardia 181 ± 33 ms, fibrillation 152 ± 23 ms, p < 0.001) and at epicardial mapping (tachycardia 210 ± 17 ms, fibrillation 192 ± 17 ms, p < 0.02). Left ventricular ejection fraction was lower in patients with spontaneous ventricular tachycardia (0.22 ± 0.09) than in patients with spontaneous ventricular fibrillation (0.27 ± 0.09) (p < 0.05).The patients with both spontaneous and inducible ventricular fibrillation had a shorter ventricular activation time on the signal-averaged ECG (129 ± 17 ms) and a higher ejection fraction (0.36 ± 0.05) than did either patients with spontaneous ventricular fibrillation and inducible ventricular tachycardia (158 ± 21 ms and 0.25 ± 0.08, respectively, each p < 0.01) or patients with both spontaneous and inducible ventricular tachycardia (181 ± 33 ms and 0.22 ± 0.09, respectively, each p < 0.001). Of the patients with inducible ventricular tachycardia, presentation with tachycardia rather than fibrillation was associated with a longer ventricular activation time on the signal-averaged ECG (181 ± 33 versus 158 ± 21 ms, p < 0.02) and a longer cycle length of inducible ventricular tachycardia (290 ± 61 versus 259 ± 44 ms, p = 0.05).In conclusion, conduction delay during sinus rhythm and left ventricular dysfunction appear to be greatest in patients with spontaneous and inducible ventricular tachycardia, and least in patients with spontaneous and inducible ventricular fibrillation

Depression at Work, Authenticity in Question: Experiencing, Concealing and Revealing

Australia and the UK have both introduced policies to protect employees who experience mental illness, including depression. However, a better understanding of the issues workers face (e.g. sense of moral failure) is needed for the provision of appropriate and beneficial support. We analysed 73 interviews from the UK and Australia where narratives of depression and work intersected. Participants encountered difficulties in being (and performing as if) ‘authentic’ at work, with depression contributing to confusions about the self. The diffuse post-1960s imperative to ‘be yourself’ is experienced in conflicting ways: While some participants sought support from managers and colleagues (e.g. sick leave, back to work plans), many others put on a façade in an attempt to perform the ‘well’ and ‘authentic’ employee. We outline the contradictory forces at play for participants when authenticity and visibility are expected, yet moral imperatives to be good (healthy) employees are normative

Toward Engineering Biosystems With Emergent Collective Functions

Many complex behaviors in biological systems emerge from large populations of interacting molecules or cells, generating functions that go beyond the capabilities of the individual parts. Such collective phenomena are of great interest to bioengineers due to their robustness and scalability. However, engineering emergent collective functions is difficult because they arise as a consequence of complex multi-level feedback, which often spans many length-scales. Here, we present a perspective on how some of these challenges could be overcome by using multi-agent modeling as a design framework within synthetic biology. Using case studies covering the construction of synthetic ecologies to biological computation and synthetic cellularity, we show how multi-agent modeling can capture the core features of complex multi-scale systems and provide novel insights into the underlying mechanisms which guide emergent functionalities across scales. The ability to unravel design rules underpinning these behaviors offers a means to take synthetic biology beyond single molecules or cells and toward the creation of systems with functions that can only emerge from collectives at multiple scales