Large-scale calibration and simulation of COVID-19 epidemiologic scenarios to support healthcare planning.

The COVID-19 pandemic has provided stiff challenges for planning and resourcing in health services in the UK and worldwide. Epidemiological models can provide simulations of how infectious disease might progress in a population given certain parameters. We adapted an agent-based model of COVID-19 to inform planning and decision-making within a healthcare setting, and created a software framework that automates processes for calibrating the model parameters to health data and allows the model to be run at national population scale on National Health Service (NHS) infrastructure. We developed a method for calibrating the model to three daily data streams (hospital admissions, intensive care occupancy, and deaths), and demonstrate that on cross-validation the model fits acceptably to unseen data streams including official estimates of COVID-19 incidence. Once calibrated, we use the model to simulate future scenarios of the spread of COVID-19 in England and show that the simulations provide useful projections of future COVID-19 clinical demand. These simulations were used to support operational planning in the NHS in England, and we present the example of the use of these simulations in projecting future clinical demand during the rollout of the national COVID-19 vaccination programme. Being able to investigate uncertainty and test sensitivities was particularly important to the operational planning team. This epidemiological model operates within an ecosystem of data technologies, drawing on a range of NHS, government and academic data sources, and provides results to strategists, planners and downstream data systems. We discuss the data resources that enabled this work and the data challenges that were faced.

Spatial-temporal contrast sensitivity of the eye alignment reflex.

The binocular alignment of the eyes involves both voluntary and reflexive mechanisms, but little is known about the visual input and neurological pathway of the reflex component. Our studies examined the role of spatiotemporal frequency and contrast in the control of reflex eye alignment, and compared the contrast sensitivity of the alignment reflex with psychophysical contrast sensitivity. We measured the contrast sensitivity of vertical disparity-driven vergence eye movements in response to bandwidth filtered static or 6 Hz counterphase flickering noise and measured psychophysical detection sensitivity for the same stimuli. Contrast thresholds for producing a detectable vertical alignment change (measured with nonius lines) were determined using a staircase method for 7 spatial frequencies [0.25-16 cycles per degree] and 3 vertical disparities [5, 10, and 30 arcmin] in 7 adults with normal or corrected to normal vision. The main findings of this study are, (1) the vertical alignment reflex had overall relatively high contrast sensitivity, comparable to but somewhat less than visual detection thresholds, (2) the most effective stimulus spatial frequency scaled in inverse proportion to the disparity being stimulated, and (3) unlike psychophysical contrast sensitivity, the eye alignment reflex contrast sensitivity was not improved by flickering low spatial frequencies.

Can Bodybuilding Peak Week Manipulations Favorably Affect Muscle Size, Subcutaneous Thickness, and Related Body Composition Variables? A Case Study.

BACKGROUND: The purpose of this case study was to implement an evidence-based dietary approach to peaking for a bodybuilding competition and monitor its impact on body composition, muscle thickness (MT), intra-to-extra-cellular fluid shifts, subcutaneous thickness (ST), and hydration status. Secondarily, to document any adverse events of this peak week approach in a small, controlled setting. Methods Dietary practices were recorded, and laboratory testing was conducted throughout peak week, including competition morning. Assessments included: dual-energy X-ray absorptiometry (DEXA) for body composition, B-mode ultrasound for MT and ST, bioimpedance spectroscopy (BIS) for total body water (TBW)/intracellular water (ICW)/extracellular water (ECW), and raw BIS data (i.e., resistance, reactance, and phase angle), urine specific gravity (USG) for hydration status, and subjective fullness. Sequential dietary manipulations were made (i.e., CHO depletion/fat loading, CHO/water loading, and a refinement phase) with specific physiological goals. This was reflected in changes observed across all assessments throughout the peak week. RESULTS: From the carbohydrate-depleted state (three days out) to competition day, we observed increases in lean body mass, MT, TBW (primarily ICW), and subjective fullness. Kendall's Tau B revealed a strong relationship between carbohydrate intake and ∑MT (τ = 0.733, p = 0.056). Additionally, novel ST data demonstrated a 10% reduction for the summation of all seven sites, with some drastic changes in specific regions (e.g., -43% for triceps ST) from three days out to competition day. CONCLUSIONS: These data suggest that the prototypical goals of bodybuilders' peak week (i.e., increasing muscle fullness, decreasing subcutaneous thickness) to enhance their aesthetics/muscularity presented can be achieved with a drug-free protocol involving dietary manipulations.

Unreferenced spatial localization under monocular and dichoptic viewing conditions.

Knowledge of eye position in the brain is critical for localization of objects in space. To investigate the accuracy and precision of eye position feedback in an unreferenced environment, subjects with normal ocular alignment attempted to localize briefly presented targets during monocular and dichoptic viewing. In the task, subjects' used a computer mouse to position a response disk at the remembered location of the target. Under dichoptic viewing (with red (right eye)-green (left eye) glasses), target and response disks were presented to the same or alternate eyes, leading to four conditions [green target-green response cue (LL), green-red (LR), red-green (RL), and red-red (RR)]. Time interval between target and response disks was varied and localization errors were the difference between the estimated and real positions of the target disk. Overall, the precision of spatial localization (variance across trials) became progressively worse with time. Under dichoptic viewing, localization errors were significantly greater for alternate-eye trials as compared to same-eye trials and were correlated to the average phoria of each subject. Our data suggests that during binocular dissociation, spatial localization may be achieved by combining a reliable versional efference copy signal with a proprioceptive signal that is unreliable perhaps because it is from the wrong eye or is too noisy.

Peak week recommendations for bodybuilders: an evidence based approach.

Bodybuilding is a competitive endeavor where a combination of muscle size, symmetry, "conditioning" (low body fat levels), and stage presentation are judged. Success in bodybuilding requires that competitors achieve their peak physique during the day of competition. To this end, competitors have been reported to employ various peaking interventions during the final days leading to competition. Commonly reported peaking strategies include altering exercise and nutritional regimens, including manipulation of macronutrient, water, and electrolyte intake, as well as consumption of various dietary supplements. The primary goals for these interventions are to maximize muscle glycogen content, minimize subcutaneous water, and reduce the risk abdominal bloating to bring about a more aesthetically pleasing physique. Unfortunately, there is a dearth of evidence to support the commonly reported practices employed by bodybuilders during peak week. Hence, the purpose of this article is to critically review the current literature as to the scientific support for pre-contest peaking protocols most commonly employed by bodybuilders and provide evidence-based recommendations as safe and effective strategies on the topic.

Stimulus dependence of interocular suppression.

Interocular suppression is the phenomenon in which the signal from one eye inhibits the other eye in the presence of dissimilar images. Various clinical and laboratory-based tests have been used to assess suppression, which vary in color, contrast, and stimulus size. These stimulus variations may yield different spatial extents of suppression, which makes it difficult to compare the outcomes. To evaluate the role of stimulus characteristics, we measured the suppression zone using a binocular rivalry paradigm in normally-sighted observers by systematically varying the stimulus parameters. The stimuli consist of a constantly visible horizontal reference seen by one eye while two vertical suppressors were presented to the other eye. With a keypress, the suppressors appeared for 1 s, to induce a transient suppression zone in the middle part of the reference. Subjects adjusted the width between the suppressors to determine the zone. The zone decreased significantly with increasing spatial frequency and lower contrast. The width was 1.4 times larger than the height. The zone was smaller with negative compared to positive contrast polarity but independent of eye dominance, luminance, and colored filters. A departure from scale invariance was captured with a model suggesting a stimulus-dependent and a small fixed non-stimulus-dependent portion.

Fixational microsaccades: A quantitative and objective measure of disability in multiple sclerosis.

BACKGROUND: Objective tools for prognosis and disease progression monitoring in multiple sclerosis (MS) are lacking. The visuomotor system could be used to track motor dysfunction at the micron scale through the monitoring of fixational microsaccades. AIMS: The aim of this study was to evaluate whether microsaccades are correlated with standard MS disability metrics and to assess whether these methods play a predictive role in MS disability. METHOD: We used a custom-built retinal eye tracker, the tracking scanning laser ophthalmoscope (TSLO), to record fixation in 111 participants with MS and 100 unaffected controls. RESULTS: In MS participants, a greater number of microsaccades showed significant association with higher Expanded Disability Status Scale score (EDSS, p < 0.001), nine-hole peg test (non-dominant: p = 0.006), Symbol Digit Modalities Test (SMDT, p = 0.014), and Functional Systems Scores (FSS) including brainstem (p = 0.005), cerebellar (p = 0.011), and pyramidal (p = 0.009). Both brainstem FSS and patient-reported fatigue showed significant associations with microsaccade number, amplitude, and peak acceleration. Participants with MS showed a statistically different average number (p = 0.020), peak vertical acceleration (p = 0.003), and vertical amplitude (p < 0.001) versus controls. Logistic regression models for MS disability were created using TSLO microsaccade metrics and paraclinical tests with ⩾80% accuracy. CONCLUSION: Microsaccades provide objective measurements of MS disability level and disease worsening.

Impact of simulated micro-scotomas on reading performance in central and peripheral retina.

Observers with central field loss typically fixate within a non-foveal region called the preferred retinal locus, which can include localized sensitivity losses, or micro-scotomas (Krishnan and Bedell, 2018). In this study, we simulated micro-scotomas at the fovea and in the peripheral retina to assess their impact on reading speed. Ten younger (<36 years old) and 8 older (>50 years old) naïve observers with normal vision monocularly read high and/or low contrast sentences, presented at or above the critical print size for young observers at the fovea and at 5 and 10 deg in the inferior visual field. Reading material comprised MNREAD sentences and sentences taken from novels that were presented in rapid serial visual presentation (RSVP) format. Randomly distributed 13 × 13 arc min blocks corresponding to 0-78% of the text area (corresponding to ∼0-17 micro-scotomas/deg2) were set to the background luminance to simulate micro-scotomas. A staircase algorithm estimated maximum reading speed from the threshold exposure duration for each combination of retinal eccentricity, contrast and micro-scotoma density in both age groups. Log10(RSVP reading speed) decreased significantly with simulated micro-scotoma density and eccentricity. Across conditions, reading speed was slower with low-compared to high-contrast text and was faster in younger than older normal observers. For a given eccentricity and contrast, a higher density of random element losses maximally affected older observers with normal vision. These outcomes may explain some of the reading deficits observed in older observers with central field loss.

Bladder debris on ultrasound as a predictor for positive urine culture in a pediatric population.

INTRODUCTION: Debris within the bladder is commonly seen on ultrasound. The etiology of bladder debris is varied and the likelihood that urinary debris represents positive urine culture is under investigation. We hypothesize that bladder debris will increase the likelihood that a urine culture is positive compared to those without bladder debris. METHODS: We performed a retrospective review on children aged 0-17 years who had a voiding cystourethrogram with a catheterized urinalysis or urine culture, and who also had a renal and bladder ultrasound up to 1 week prior, the day of, or up to 2 days after their urine studies. Presence of bladder debris and debris severity was recorded. Positive urine culture was defined as a single bacterial strain ≥50,000 cfu/mL. Demographic information, including findings of reflux and hydronephrosis were compared. Sensitivity, specificity, and risk ratios were calculated for predicting positive urine culture in patients with urinary debris on ultrasound. RESULTS: A total of 445 patients met inclusion criteria between January and December 2014. The positive urine culture rate was 20%, and the rate of bladder debris was 22%. The mean age for those with and without bladder debris was 6.6 and 5.5 years, respectively (p = 0.02). 23% of girls had bladder debris, compared to 12% of boys (p = 0.04, see results table). The sensitivity and specificity for bladder debris in detecting positive urine cultures was 52% and 86%, respectively. Forty-seven percent of those with bladder debris had positive cultures, compared with 12% of those without debris (p < 0.01). The relative risk of positive urine culture if debris is present is 3.90 (95% CI 2.73-5.55). Hydronephrosis or vesicoureteral reflux did not affect the relationship between bladder debris and positive urine cultures. CONCLUSIONS: Nearly half of pediatric patients undergoing urological evaluation found to have bladder debris on ultrasound will have a positive urine culture. Debris is noted more commonly in girls and at a slightly higher age. The presence of debris is associated with a fourfold increase in detecting a positive urine culture, regardless of debris severity, hydronephrosis, or vesicoureteral reflux. Given this, it is of value to routinely document and look for the presence of any amount of bladder debris seen on ultrasound, as this finding can be used to augment clinical decision-making and warrants strong consideration for obtaining urine culture.

Blur Detection, Depth of Field, and Accommodation in Emmetropic and Hyperopic Children.

SIGNIFICANCE: Our results demonstrate that blur detection thresholds are elevated in young children compared with adults, and poorer blur detection thresholds are significantly correlated with the magnitude of accommodative microfluctuations. Given that accommodative microfluctuations are greater with greater accommodative responses, these findings may have implications for young uncorrected hyperopes. PURPOSE: This study investigated the association between subjective blur detection thresholds and accommodative microfluctuations in children 3 years to younger than 10 years old and adults. METHODS: Blur detection thresholds were determined in 49 children with habitually uncorrected refractive error (+0.06 to +4.91 diopters [D] spherical equivalent) and 10 habitually uncorrected adults (+0.08 to +1.51 D spherical equivalent) using a custom blur chart with 1° sized optotypes at 33 cm. Letters were blurred by convolution using a Gaussian kernel (SDs of 0.71 to 11.31 arc minutes in √2 steps). Subjective depth of field was determined in subjects 6 years or older and adults. Accommodative microfluctuations, pupils, and lag were measured using infrared photorefraction (25 Hz). RESULTS: Children had greater blur detection thresholds (P < .001), accommodative microfluctuations (P = .001), and depth of field (P < .001) than adults. In children, increased blur detection thresholds were associated with increased accommodative microfluctuations (P < .001), increased uncorrected hyperopia (P = .01), decreased age (P < .001), and decreased pupil size (P = .01). In a multiple linear regression analysis, blur detection thresholds were associated with accommodative microfluctuations (P < .001) and age (P < .001). Increased accommodative microfluctuations were associated with increased uncorrected hyperopia (P = .004) and decreased pupil size (P = .003) and independently associated with uncorrected hyperopia (P = .001) and pupil size (P = .003) when controlling for age and lag. CONCLUSIONS: Children did not have adult-like blur detection thresholds or depth of field. Increased accommodative microfluctuations and decreased age were independently associated with greater blur detection thresholds in children 3 years to younger than 10 years. Larger amounts of uncorrected hyperopia in children appear to increase blur detection thresholds because the greater accommodative demand and resulting response increase accommodative microfluctuations.

The influence of endogenous attention on contrast perception, contrast discrimination, and saccadic reaction time.

Visual spatial attention has been shown to influence both contrast detection and suprathreshold contrast perception, as well as manual and saccadic reaction times (SRTs). Because SRTs are influenced also by stimulus contrast, we investigated if the enhancement of perceived contrast that accompanies attention could account for the shorter SRTs observed for attended targets locations. We conducted two dual-task experiments to assess psychophysical and oculomotor responses to non-foveal targets of various contrast for different spatial-attention-cueing conditions. Cues were either: valid, an arrow at fixation pointing in the direction of the upcoming target; invalid, an arrow pointing in a different direction from the target; or neutral, a small circle instead of an arrow. In both experiments, subjects were instructed to make a saccade to the location of a subsequent, briefly flashed target. In the first experiment, the psychophysical judgment was a two-alternative-forced-choice (2AFC) contrast-detection task, in which subjects reported whether the flashed target was at a near (3°) or far (6°) eccentricity. In the second experiment, the judgment was a contrast matching task, in which subjects reported whether the target's contrast was higher or lower than a remembered standard contrast. The results exhibit a robust, ∼40-50 ms reduction of SRTs with a valid compared to an invalid cue. Cueing effects on contrast detection and matching were small and inconsistent across subjects. Hence, the observed decrease in SRTs could not be accounted for fully by an enhancement in the target's effective contrast due to attention, as attended and unattended targets that were equally detectable or were perceived to have the same suprathreshold contrast showed substantial differences in SRT.

Scotoma Visibility and Reading Rate with Bilateral Central Scotomas.

PURPOSE: In this experiment, we tested whether perceptually delineating the scotoma location and border with a gaze contingent polygon overlay improves reading speed and reading eye movements in patients with bilateral central scotomas. METHODS: Eight patients with age-related macular degeneration and bilateral central scotomas read aloud MNRead style sentences with their preferred eye. Eye movement signals from an EyeLink II eyetracker were used to create a gaze contingent display in which a polygon overlay delineating the area of the patient's scotoma was superimposed on the text during 18 of the 42 trials. Blocks of six trials with the superimposed polygon were alternated with blocks of six trials without the polygon. Reading speed and reading eye movements were assessed before and after the subjects practiced reading with the polygon overlay. RESULTS: All of the subjects but one showed an increase in reading speed. A paired-samples t-test for the group as a whole revealed a statistically significant increase in reading speed of 0.075 ± 0.060 (SD) log wpm after reading with the superimposed polygon. Individual subjects demonstrated significant changes in reading eye movements, with the greatest number of subjects demonstrating a shift in the average vertical fixation locus. Across subjects, there was no significant difference between the initial and final reading eye movements in terms of saccades per second, average fixation duration, average amplitude of saccades, or proportion of non-horizontal saccades. CONCLUSIONS: The improvement in reading speed (0.075 log wpm or 19%) over the short experimental session for the majority of subjects indicates that making the scotoma location more visible is potentially beneficial for improving reading speed in patients with bilateral central scotomas. Additional research to examine the efficacy of more extended training with this paradigm is warranted.

Epidemiology and Diagnosis of Testis Cancer.

Testis cancer is the most commonly diagnosed cancer in young men. Most cases represent sporadic occurrences. Most commonly it presents at an early stage (clinical stage I) and is highly curable with radical orchiectomy. Even more advanced stages of testicular cancer are curable with a multimodality treatment approach. There are no widely accepted screening strategies for germ cell tumors. This article discusses the known risk factors and epidemiology of testis cancer, the presentation, and work up for new patients, and the prognosis and cure rates based on the staging and current treatment modalities for testis cancer patients.

Progress on Developing Adaptive Optics-Optical Coherence Tomography for In Vivo Retinal Imaging: Monitoring and Correction of Eye Motion Artifacts.

Recent progress in retinal image acquisition techniques, including optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO), combined with improved performance of adaptive optics (AO) instrumentation, has resulted in improvement in the quality of in vivo images of cellular structures in the human retina. Here, we present a short review of progress on developing AO-OCT instruments. Despite significant progress in imaging speed and resolution, eye movements present during acquisition of a retinal image with OCT introduce motion artifacts into the image, complicating analysis and registration. This effect is especially pronounced in high-resolution datasets acquired with AO-OCT instruments. Several retinal tracking systems have been introduced to correct retinal motion during data acquisition. We present a method for correcting motion artifacts in AO-OCT volume data after acquisition using simultaneously captured adaptive optics-scanning laser ophthalmoscope (AO-SLO) images. We extract transverse eye motion data from the AO-SLO images, assign a motion adjustment vector to each AO-OCT A-scan, and re-sample from the scattered data back onto a regular grid. The corrected volume data improve the accuracy of quantitative analyses of microscopic structures.

Cost-effectiveness of neoadjuvant chemotherapy before radical cystectomy for muscle-invasive bladder cancer.

OBJECTIVES: To determine the costs of treatment and the duration of survival, adjusted for quality of life, for patients with muscle-invasive bladder cancer treated with immediate radical cystectomy (RC) or with neoadjuvant chemotherapy (NAC) with intent for subsequent RC. METHODS AND MATERIALS: A retrospective review of our institutional review board-approved database identified patients with muscle-invasive bladder cancer treated at our institution from 2004 to 2011. Patients were divided into those receiving RC alone and those receiving NAC before planned RC. Patients who refused RC following NAC were included in an intention-to-treat analysis. Survival duration was converted to quality-adjusted life years (QALYs), and costs of treatment per QALY were determined. RESULTS: A total of 119 patients (65.4%) received RC alone and 63 (34.6%) received NAC, 38 of whom proceeded to cystectomy as planned. Mean total costs were $42,890 and $52,429 for RC and NAC, respectively (P = 0.005). The 5-year overall survival was 31.7% and 42.5% for the RC-only group and the NAC group, respectively (P = 0.034). The 5-year overall survival measured in QALYs was 21.9% and 42.9% for the RC-only and the NAC groups, respectively (P = 0.021). The increased cost for NAC was $5,840 per additional life year gained (95% CI: $1,772-$9,909) and $6,187 per additional QALY gained (95% CI: $1,877-$10,498). CONCLUSIONS: The use of NAC is associated with a significant increase in quality-adjusted survival. The additional cost per QALY gained is approximately $6,000. The cost-utility analysis of NAC compares favorably with other cancer-specific therapies.

How the unstable eye sees a stable and moving world.

Eye motion, even during fixation, results in constant motion of the image of the world on our retinas. Vision scientists have long sought to understand the process by which we perceive the stable parts of the world as unmoving despite this instability and perceive the moving parts with realistic motion. We used an instrument capable of delivering visual stimuli with controlled motion relative to the retina at cone-level precision while capturing the subjects' percepts of stimulus motion with a matching task. We found that the percept of stimulus motion is more complex than conventionally thought. Retinal stimuli that move in a direction that is consistent with eye motion (i.e., opposite eye motion) appear stable even if the magnitude of that motion is amplified. The apparent stabilization diminishes for stimulus motions increasingly inconsistent with eye motion direction. Remarkably, we found that this perceived direction-contingent stabilization occurs separately for each separately moving pattern on the retina rather than for the image as a whole. One consequence is that multiple patterns that move at different rates relative to each other in the visual input are perceived as immobile with respect to each other, thereby disrupting our hyperacute sensitivity to target motion against a frame of reference. This illusion of relative stability has profound implications regarding the underlying visual mechanisms. Functionally, the system compensates retinal slip induced by eye motion without requiring an extremely precise optomotor signal and, at the same time, retains an exquisite sensitivity to an object's true motion in the world.

Eye movement testing in clinical examination.

The clinical vision examination routinely includes an evaluation of ocular motor function. In a number of diverse situations, thorough objective recording of eye movements is warranted, using any of a variety of eye-tracking technologies that are available currently to clinicians. Here we review the clinical uses of eye tracking, with both an historical and contemporary view. We also consider several new imaging technologies that are becoming available in clinics and include inbuilt eye-tracking capability. These highly sensitive eye trackers should be useful for evaluating a variety of subtle, but important, oculomotor signs and disorders.

Nonequilibrium electron rings for synchrotron radiation production.

Electron storage rings used for the production of synchrotron radiation (SR) have an output photon brightness that is limited by the equilibrium beam emittance. By using interleaved injection and ejection of bunches from a source with repetition rate greater than 1 kHz, we show that it is practicable to overcome this limit in rings of energy ∼1 GeV. Sufficiently short kicker pulse lengths enable effective currents of many milliamperes, which can deliver a significant flux of diffraction-limited soft x-ray photons. Thus, either existing SR facilities may be adapted for nonequilibrium operation, or the technique applied to construct SR rings smaller than their storage ring equivalent.

Improved removal rates for retrievable inferior vena cava filters with the use of a 'filter registry'.

The American Association for the Surgery of Trauma challenged the trauma community to improve a 22 per cent average removal rate for retrievable inferior vena cava filters (r-IVCFs). Since 2006, we maintained a "filter registry" documenting all IVCFs placed in trauma patients. Our goal was to improve removal rates for r-IVCF. Patients receiving an IVCF before implementation of filter registry, 2003-2005, comprised the control group. Patients receiving an IVCF after implementation of filter registry, 2006-2009, comprised the study group. Data obtained included age, gender, Injury Severity Score (ISS), length of stay (LOS), mortality, filter inserted, placement indication, removal rates, and reasons why removal did not occur. Fisher exact test and chi square were used for nominal variables. Stepwise logistic regression analysis was used to define predictors of removing and not removing an IVCF. Three hundred seven patients received an IVCF, 142 preregistry and 165 postregistry. No significant difference existed between groups in age, gender, ISS, placement indication, or mortality. A significant difference existed between groups in LOS and presence of deep vein thrombosis (DVT) and pulmonary embolism. A total of 98.2 per cent of postregistry patients received a Günther Tulip filter and all retrievals were performed by Interventional Radiology. Retrieval rates improved, 15.5 to 31.5 per cent post registry (P < 0.001). No differences existed in lost to follow-up (LTF) between groups. Univariate analysis identified age, IVC clot, DVT, and LTF as predictors for not removing a filter. Stepwise logistic regression revealed the filter registry independently predicts the removal of an r-IVCF. A filter registry is effective in improving rates of removal for r-IVCFs.