Engineered jumpers overcome biological limits via work multiplication.

For centuries, scientists have explored the limits of biological jump height1,2, and for decades, engineers have designed jumping machines3-18 that often mimicked or took inspiration from biological jumpers. Despite these efforts, general analyses are missing that compare the energetics of biological and engineered jumpers across scale. Here we show how biological and engineered jumpers have key differences in their jump energetics. The jump height of a biological jumper is limited by the work its linear motor (muscle) can produce in a single stroke. By contrast, the jump height of an engineered device can be far greater because its ratcheted or rotary motor can 'multiply work' during repeated strokes or rotations. As a consequence of these differences in energy production, biological and engineered jumpers should have divergent designs for maximizing jump height. Following these insights, we created a device that can jump over 30 metres high, to our knowledge far higher than previous engineered jumpers and over an order of magnitude higher than the best biological jumpers. Our work advances the understanding of jumping, shows a new level of performance, and underscores the importance of considering the differences between engineered and biological systems.

[Illustration Techniques in Ophthalmic Textbooks 200 Years Ago - a Platform for the Rostock Glass Eye Collection of Anterior Segment Pathologies from 1860]. / Ophthalmologische Abbildungstechnik vor 200 Jahren ­ der Atlas von Antoine Pierre Demours als Grundlage der Rostocker Kunstaugensammlung.

Very recent research results have demonstrated that the "Rostock Artificial Eye Collection" - assembled 150 years ago with 132 glass modelled exhibits of anterior segment pathologies - is mainly based on the figures of the Atlas of Ophthalmology published by Antoine Pierre Demours in 1818. This article focusses on the analyses of the imaging techniques of this atlas. Present knowledge implies that the author used different colour etching concepts which were partially re-coloured individually. In the opinion of contemporaries, the figures of Demours' atlas represent the climax of scientific imaging techniques. In the academic literature, it is still described as a "recent remarkable masterpiece", even 100 years later.

Feedback control of acoustic musical instruments: collocated control using physical analogs.

Traditionally, the average professional musician has owned numerous acoustic musical instruments, many of them having distinctive acoustic qualities. However, a modern musician could prefer to have a single musical instrument whose acoustics are programmable by feedback control, where acoustic variables are estimated from sensor measurements in real time and then fed back in order to influence the controlled variables. In this paper, theory is presented that describes stable feedback control of an acoustic musical instrument. The presentation should be accessible to members of the musical acoustics community who may have limited or no experience with feedback control. First, the only control strategy guaranteed to be stable subject to any musical instrument mobility is described: the sensors and actuators must be collocated, and the controller must emulate a physical analog system. Next, the most fundamental feedback controllers and the corresponding physical analog systems are presented. The effects that these controllers have on acoustic musical instruments are described. Finally, practical design challenges are discussed. A proof explains why changing the resonance frequency of a musical resonance requires much more control power than changing the decay time of the resonance.

Laser-Machined Shape Memory Alloy Sensors for Position Feedback in Active Catheters.

Catheter-based interventions are a form of minimally invasive surgery that can decrease hospitalization time and greatly lower patient morbidity compared to traditional methods. However, percutaneous catheter procedures are hindered by a lack of precise tip manipulation when actuation forces are transmitted over the length of the catheter. Active catheters with local shape-memory-alloy (SMA) actuation can potentially provide the desired manipulation of a catheter tip, but hysteresis makes it difficult to control the actuators. A method to integrate small-volume, compliant sensors on an active catheter to provide position feedback for control would greatly improve the viability of SMA-based active catheters. In this work, we describe the design, fabrication, and performance of resistance-based position sensors that are laser-machined from superelastic SMA tubing. Combining simple material models and rapid prototyping, we can develop sensors of appropriate stiffness and sensitivity with simple modifications in sensor geometry. The sensors exhibit excellent linearity over the operating range and are designed to be easily integrated onto an active catheter substrate.

Quantitative analysis of OCT characteristics in patients with achromatopsia and blue-cone monochromatism.

PURPOSE: To quantify optical coherence tomography (OCT) images of the central retina in patients with blue-cone monochromatism (BCM) and achromatopsia (ACH) compared with healthy control individuals. METHODS: The study included 15 patients with ACH, 6 with BCM, and 20 control subjects. Diagnosis of BCM and ACH was established by visual acuity testing, morphologic examination, color vision testing, and Ganzfeld ERG recording. OCT images were acquired with the Stratus OCT 3 (Carl Zeiss Meditec AG, Oberkochen, Germany). Foveal OCT images were analyzed by calculating longitudinal reflectivity profiles (LRPs) from scan lines. Profiles were analyzed quantitatively to determine foveal thickness and distances between reflectivity layers. RESULTS: Patients with ACH and BCM had a mean visual acuity of 20/200 and 20/60, respectively. Color vision testing results were characteristic of the diseases. The LRPs of control subjects yielded four peaks (P1-P4), presumably representing the RPE (P1), the ovoid region of the photoreceptors (P2), the external limiting membrane (ELM) (P3), and the internal limiting membrane (P4). In patients with ACH, P2 was absent, but foveal thickness (P1-P4) did not differ significantly from that in the control subjects (187 +/- 20 vs. 192 +/- 14 microm, respectively). The distance from P1 to P3 did not differ significantly (78 +/- 10 vs. 82 +/- 5 microm) between ACH and controls subjects. In patients with BCM, P3 was lacking, and P2 advanced toward P1 compared with the control subjects (32 +/- 6 vs. 48 +/- 4 microm). Foveal thickness (153 +/- 16 microm) was significantly reduced compared with that in control subjects and patients with ACH. CONCLUSIONS: Quantitative OCT image analysis reveals distinct patterns for controls subjects and patients with ACH and BCM, respectively. Quantitative analysis of OCT imaging can be useful in differentiating retinal diseases affecting photoreceptors. Foveal thickness is similar in both normal subjects and patients with ACH but is decreased in patients with BCM.

Improving contact realism through event-based haptic feedback.

Tapping on surfaces in a typical virtual environment feels like contact with soft foam rather than a hard object. The realism of such interactions can be dramatically improved by superimposing event-based, high-frequency transient forces over traditional position-based feedback. When scaled by impact velocity, hand-tuned pulses and decaying sinusoids produce haptic cues that resemble those experienced during real impacts. Our new method for generating appropriate transients inverts a dynamic model of the haptic device to determine the motor forces required to create prerecorded acceleration profiles at the user's fingertips. After development, the event-based haptic paradigm and the method of acceleration matching were evaluated in a carefully controlled user study. Sixteen individuals blindly tapped on nine virtual and three real samples, rating the degree to which each felt like real wood. Event-based feedback achieved significantly higher realism ratings than the traditional rendering method. The display of transient signals made virtual objects feel similar to a real sample of wood on a foam substrate, while position feedback alone received ratings similar to those of foam. This work provides an important new avenue for increasing the realism of contact in haptic interactions.

Cross-sectional study of visual acuity and electroretinogram in two types of dominant drusen.

PURPOSE: To compare the changes with increasing age of ERG parameters in relation to clinical data in two distinct phenotypes of genetically determined, dominantly inherited macular drusen: malattia leventinese (ML) and Zermatt macular dystrophy (ZMD). METHODS: Ganzfeld rod- and cone-electroretinograms (ERGs) from 15 patients affected with ML and 14 patients with ZMD and clinical data were analyzed retrospectively. The patients' ages ranged from 20 to 77 years in the ML group and from 9 to 74 years in the ZMD group. RESULTS: Both inherited macular degenerations caused a marked decrease in visual acuity, the latest after age 65. Most patients with ML retained good visual function (0.8-1.0) until the fifth decade, followed by a rapid decrease in the fifth or sixth decade. ZMD is characterized by a relatively continuous decrease in visual acuity with increasing age. Morphologically, in the juvenile stages in both entities, drusen were observed at the posterior pole. Rod-driven and cone-driven ERG b-wave amplitudes decreased nearly linearly in ML and ZMD in accord with the normal loss of amplitude with increasing age. Implicit times of cone b-waves for ML increased markedly with age, whereas in ZMD the values were always prolonged beyond the normal range with a slight increase with age. CONCLUSIONS: In terms of visual acuity, the progression of both dominantly inherited macular dystrophies is quite different. This is not reflected in the amplitudes of the b-waves in the Ganzfeld ERGs, which decrease normally for both entities. Implicit times of the cone-b waves were more markedly prolonged in ML compared with ZMD. In-depth longitudinal documentation of the natural course of those dominantly inherited macular diseases should facilitate patient counseling.

Clinical description and exclusion of candidate genes in a novel autosomal recessively inherited vitreoretinal dystrophy.

OBJECTIVES: To describe the clinical phenotype of a novel autosomal recessively inherited vitreoretinal dystrophy in one generation of a family originating from eastern Switzerland. METHODS: A clinical study including electroretinographic investigations followed by laboratory-based genetic and molecular analysis. Four affected and 3 unaffected members of the family were examined. Ten candidate regions were tested by linkage analysis with highly polymorphic molecular markers or with intragenic restriction fragment length polymorphisms. RESULTS: Of 8 siblings,4 were affected, showing high myopia with pronounced vitreous liquefaction, retinitis pigmentosa-like retinal degeneration, diffuse retinal pigment epithelium atrophy, macular staphylomata, and premature cataract formation. Strikingly abnormal results on electroretinograms, affecting both the rod and the cone systems, revealed an extensive defect of retinal function, unlike those usually found in pathologic myopia. No extraocular manifestations were observed. Three types of nonsyndromic high myopia, Stickler syndrome I, II, and III, Wagner syndrome, Knobloch syndrome, Goldmann-Favre dystrophy, and multiple vitreoretinopathies were excluded by linkage analysis. CONCLUSIONS: The reported phenotype as well as the results of molecular linkage analysis in the siblings described here suggest an autosomal recessively inherited vitreoretinal dystrophy, which, to our knowledge, has not been described until now.

Absolute sensitivity of the electroretinogram and of the optic nerve action potential in the perfused feline eye.

PURPOSE: To assess and characterize the electroretinogram (ERG) and the optic nerve response (ONR) at threshold stimulus intensity in the isolated perfused cat eye. METHODS: Eyes were enucleated from deeply anesthetized adult cats and arterially perfused with oxygenated serum-enriched tissue culture medium. Light stimuli of 20- to 400- msec duration from a xenon arc source, attenuated down to threshold intensities by neutral density filters, were delivered via a modified fundus camera in full dark adaptation. Vitreal ERGs and ONRs were amplified, digitized, averaged and analyzed using LabVIEW for Windows software. RESULTS: The threshold intensities in log scot q/deg(2) per second for the negative scotopic threshold response (STR), for the ERG b-wave, and for the ONR were at 2.87+/-0.35, 3.53+/-0.35 and 1.78+/-0.48, respectively. CONCLUSION: The in vitro perfused mammalian eye preparation exhibits remarkably low thresholds for the ERG and particularly for the ONR near the intensity required for the human psychophysical threshold.

THUMP: an immersive haptic console for surgical simulation and training.

Telerobotic systems are revolutionizing minimally invasive surgery (MIS), giving the surgeon complete control over precise dexterous movements of tiny robotic instruments. Such 'surgery-by-wire' approaches also create unique opportunities for simulation and training, as the surgeon operates at a computer-mediated haptic console. Possible extensions include offline training in simulated environments and advanced guidance and mentoring during actual operations. To explore these options and further improve telerobotic interfaces, we have constructed a two-handed, fully articulating haptic console that provides force and torque feedback as well as a stereoscopic display.

Inpatient trial of an artificial pancreas based on multiple model probabilistic predictive control with repeated large unannounced meals.

BACKGROUND: Closed-loop control of blood glucose levels in people with type 1 diabetes offers the potential to reduce the incidence of diabetes complications and reduce the patients' burden, particularly if meals do not need to be announced. We therefore tested a closed-loop algorithm that does not require meal announcement. MATERIALS AND METHODS: A multiple model probabilistic predictive controller (MMPPC) was assessed on four patients, revised to improve performance, and then assessed on six additional patients. Each inpatient admission lasted for 32 h with five unannounced meals containing approximately 1 g/kg of carbohydrate per admission. The system used an Abbott Diabetes Care (Alameda, CA) Navigator(®) continuous glucose monitor (CGM) and Insulet (Bedford, MA) Omnipod(®) insulin pump, with the MMPPC implemented through the artificial pancreas system platform. The controller was initialized only with the patient's total daily dose and daily basal pattern. RESULTS: On a 24-h basis, the first cohort had mean reference and CGM readings of 179 and 167 mg/dL, respectively, with 53% and 62%, respectively, of readings between 70 and 180 mg/dL and four treatments for glucose values <70 mg/dL. The second cohort had mean reference and CGM readings of 161 and 142 mg/dL, respectively, with 63% and 78%, respectively, of the time spent euglycemic. There was one controller-induced hypoglycemic episode. For the 30 unannounced meals in the second cohort, the mean reference and CGM premeal, postmeal maximum, and 3-h postmeal values were 139 and 132, 223 and 208, and 168 and 156 mg/dL, respectively. CONCLUSIONS: The MMPPC, tested in-clinic against repeated, large, unannounced meals, maintained reasonable glycemic control with a mean blood glucose level that would equate to a mean glycated hemoglobin value of 7.2%, with only one controller-induced hypoglycemic event occurring in the second cohort.

A closed-loop artificial pancreas based on risk management.

BACKGROUND: Control algorithms that regulate blood glucose (BG) levels in individuals with type 1 diabetes mellitus face several fundamental challenges. Two of these are the asymmetric risk of clinical complications associated with low and high glucose levels and the irreversibility of insulin action when using only insulin. Both of these nonlinearities force a controller to be more conservative when uncertainties are high. We developed a novel extended model predictive controller (EMPC) that explicitly addresses these two challenges. METHOD: Our extensions to model predictive control (MPC) operate in three ways. First, they explicitly minimize the combined risk of hypoglycemia and hyperglycemia. Second, they integrate the effect of prediction uncertainties into the risk. Third, they understand that future control actions will vary if measurements fall above or below predictions. Using the University of Virginia/Padova Simulator, we compared our novel controller (EMPC) against optimized versions of a proportional-integral-derivative (PID) controller, a traditional MPC, and a basal/bolus (BB) controller, as well as against published results of an independent MPC (IMPC). The BB controller was optimized retrospectively to serve as a bound on the possible performance. RESULTS: We tuned each controller, where possible, to minimize a published blood glucose risk index (BGRI). The simulated controllers (PID/MPC/EMPC/BB) provided BGRI values of 2.99/3.05/2.51/1.27 as compared to the published IMPC BGRI value of 4.10. These correspond to 73/79/84/92% of BG values lying in the euglycemic range (70-180 mg/dl), respectively, with mean BG levels of 151/156/147/140 mg/dl. CONCLUSION: The EMPC strategy extends MPC to explicitly address the issues of asymmetric glycemic risk and irreversible insulin action using estimated prediction uncertainties and an explicit risk function. This controller reduces the avoidable BGRI by 56% (p < .05) relative to a published MPC algorithm studied on a similar population.

Probabilistic evolving meal detection and estimation of meal total glucose appearance.

BACKGROUND: Automatic compensation of meals for type 1 diabetes patients will require meal detection from continuous glucose monitor (CGM) readings. This is challenged by the uncertainty and variability inherent to the digestion process and glucose dynamics as well as the lag and noise associated with CGM sensors. Thus any estimation of meal start time, size, and shape is fundamentally uncertain. This uncertainty can be reduced, but not eliminated, by estimating total glucose appearance and using new readings as they become available. METHOD: In this article, we propose a probabilistic, evolving method to detect the presence and estimate the shape and total glucose appearance of a meal. The method is unique in continually evolving its estimates and simultaneously providing uncertainty measures to monitor their convergence. The algorithm operates in three phases. First, it compares the CGM signal to no-meal predictions made by a simple insulin-glucose model. Second, it fits the residuals to potential, assumed meal shapes. Finally, it compares and combines these fits to detect any meals and estimate the meal total glucose appearance, shape, and total glucose appearance uncertainty. RESULTS: We validate the performance of this meal detection and total glucose appearance estimation algorithm both separately and in cooperation with a controller on the Food and Drug Administration-approved University of Virginia/Padova Type I Diabetes Simulator. In cooperation with a controller, the algorithm reduced the mean blood glucose from 137 to 132 mg/dl over 1.5 days of control without any increased hypoglycemia. CONCLUSION: This novel, extensible meal detection and total glucose appearance estimation method shows the feasibility, relevance, and performance of evolving estimates with explicit uncertainty measures for use in closed-loop control of type 1 diabetes.

Statistical hypoglycemia prediction.

BACKGROUND: Hypoglycemia presents a significant risk for patients with insulin-dependent diabetes mellitus. We propose a predictive hypoglycemia detection algorithm that uses continuous glucose monitor (CGM) data with explicit certainty measures to enable early corrective action. METHOD: The algorithm uses multiple statistical linear predictions with regression windows between 5 and 75 minutes and prediction horizons of 0 to 20 minutes. The regressions provide standard deviations, which are mapped to predictive error distributions using their averaged statistical correlation. These error distributions give confidence levels that the CGM reading will drop below a hypoglycemic threshold. An alarm is generated if the resultant probability of hypoglycemia from our predictions rises above an appropriate, user-settable value. This level trades off the positive predictive value against lead time and missed events. RESULTS: The algorithm was evaluated using data from 26 inpatient admissions of Navigator(R) 1-minute readings obtained as part of a DirecNet study. CGM readings were postprocessed to remove dropouts and calibrate against finger stick measurements. With a confidence threshold set to provide alarms that correspond to hypoglycemic events 60% of the time, our results were (1) a 23-minute mean lead time, (2) false positives averaging a lowest blood glucose value of 97 mg/dl, and (3) no missed hypoglycemic events, as defined by CGM readings. Using linearly interpolated FreeStyle capillary glucose readings to define hypoglycemic events provided (1) the lead time was 17 minutes, (2) the lowest mean glucose with false alarms was 100 mg/dl, and (3) no hypoglycemic events were missed. CONCLUSION: Statistical linear prediction gives significant lead time before hypoglycemic events with an explicit, tunable trade-off between longer lead times and fewer missed events versus fewer false alarms.

ERG components of negative polarity from the inner retina and the optic nerve response.

ERG components of negative polarity in the light-adapted and in the dark-adapted inner retina are reviewed from a clinical perspective and include consideration of experimental research. Field potentials are inherently complex including summating contributions from specialized neurons as well as from glial elements. This property applies to the PERG, PhNR and to the STR. Experimental research can contribute to identifying the sites/cells of origins i.e. by determining depth profiles and by pharmacological manipulation. Intraretinal microelectrode-studies and pharmacological dissection of light-evoked responses have elucidated the origin of field potentials from the retinal pigment epithelium to the retinal ganglion cells. Thresholds for dark-adapted response components have been compared. Attenuation of the STR by anesthesia was found in cats in vivo when compared to threshold intensities used in isolated eye preparations in vitro, suggestive of depression of inner retinal activity by anesthetics. Evidence has been presented for antidromically elicited retinal responses of negative polarity that resemble the STR and summate with the light-evoked retinal response. This observation supports the notion that negative field potentials and components as recorded in the vitreous and at the cornea receive contributions from retinal ganglion cells. The weight of this contribution appears to vary among species, at least concerning the STR. The ocular negative responses from the inner retina are compared to cortical excitatory mechanisms generating negativity in the baseline of the EEG.

[Normal fundus and abnormal electroretinogram: differential diagnosis]. / Sehstörung bei unauffälligem Fundus und pathologisch verändertem Elektroretinogramm: Differenzialdiagnosen.

PURPOSE: To assess retinal dysfunction when ophthalmoscopy reveals normal features. METHODS: Ganzfeld electroretinography of the rod and of the cone systems was used to detect congenital or acquired retinal dysfunction. In infants under 5 years of age ERG was performed using inhalational anaesthesia. In addition, multifocal ERG techniques detect discrete local retinal dysfunctions. The ERG results are evaluated in comparison to normative data and to ophthalmoscopic as well as perimetric results. Patient data were selected to demonstrate typical ERG changes and the corresponding differential diagnosis. RESULTS: Abnormalities in ERG results and normal ophthalmoscopic features are shown in 8 typical examples. They were observed in the following conditions: (1) stationary congenital dysfunctions, (2) early stages of the hereditary tapetoretinal degenerations, and (3) toxic or cancer-associated retinopathies. In these disorders the ERG complemented visual field testing by detecting isolated dysfunction of the rod- and cone-systems. CONCLUSION: In the context of making crucial diagnostic decisions ERG complements ophthalmoscopy and psychophysical testing of the retinal function. This diagnostic test facilitates differential diagnosis, helps to establish prognosis, and provides a basis for genetic counselling.

[Ganzfeld and multifocal electroretinography in Malattia Leventinese and Zermatt Macular Dystrophy]. / Elektroretinographie bei zwei dominant vererbten Makulopathien.

BACKGROUND: To show the value of Ganzfeld electroretinography (ERG) in Malattia Leventinese (ML, or Hereditary Dominant Drusen) and Zermatt Macular Dystrophy (ZMD) and to illustrate multifocal electroretinography (mfERG) in 2 cases of ML. PATIENTS AND METHODS: In 15 patients with ML and 14 with ZMD we recorded Ganzfeld ERGs along with clinical examinations. In two patients with ML, and an we also performed a mfERG and an automated and Goldmann perimetry. All patients had a genotypic confirmation of the respective disease. For ERG measurements, the UTAS-3000 system was used, the mfERG was recorded using the RetiScan system. RESULTS: In ML, the visual acuity remained at 0.8 or higher until the 5 (th) or 6 (th) decade of life, followed by a rapid drop. In ZMD, the decrease in acuity began already in the 3 (rd) decade and followed a more continuous time course. The time course of the decrease of the ERG b-wave amplitudes was nearly identical for either disease. The mfERG showed in one case of ML a marked reduction in the macular response density but, in the second case, a normal density response pattern despite large degenerative changes at the posterior pole. In both of these patients, we found no visual field defects. CONCLUSIONS: Patient history and clinical testing raised the suspicion of a hereditary macular dystrophy. By means of Ganzfeld and multifocal electroretinography the course of the disease could be observed. However, definite diagnosis could only be established by genetic identification.

Multifocal electroretinogram (mfERG) in a family with occult macular dystrophy (OMD).

BACKGROUND: Localized macular dysfunction, in Stargardt macular dystrophy for example, is frequently not detected by Ganzfeld electroretinography (ERG) but it may be detected by methods such as focal macular electroretinogram and pattern electroretinogram at the posterior pole of the eye or indirectly by recording of the visual evoked cortical potentials (VEP). The multifocal electroretinogram (mfERG) is a new diagnostic tool allowing analysis of local bioelectrical signals of circumscript areas across the macular region. Miyake recently described a type of macular dystrophy, which he termed "Occult Macular Dystrophy" (OMD) because of a normal fundus aspect and functional deficit even in aged patients. This is a case report about a family with a presumed OMD where mfERG demonstrated a central depression in the affected family members. PATIENTS AND METHODS: Three members of a family with a suspected autosomal dominant trait complained of a reduced visual acuity since early childhood. The fundus of all patients appeared normal without signs of a maculopathy. The first order mfERG (ROLAND system) was recorded using 61 hexagons. RESULTS: The signals arising from the macular region of the 6 eyes (3 affected family members) were selectively depressed while the signals from the paracentral area were much less impaired. Statistical analysis of the mfERG signals (concentric hexagon rings) confirmed the central depression with a better performance of the peripheral rings. CONCLUSIONS: A new family with OMD is added to preceeding reports. A reduced visual acuity without visible fundus abnormalities may be misdiagnosed as amblyopia, optic nerve disease or nonorganic visual disorder. The mfERG offers the diagnostic tool to detect a circumscript retinal/macular dysfunction by a single procedure.

Multiple effects of adenosine in the arterially perfused mammalian eye. Possible mechanisms for the neuroprotective function of adenosine in the retina.

It has been postulated that the major physiological role of adenosine is protection of the central nervous system in conditions such as ischemia, hypoxia, or prolonged neuronal excitation. Under these conditions adenosine is released, and exerts multiple effects, including vasodilation, inhibition of neuronal activity, and enhancement of glycogenolysis, resulting in neuroprotection. In this article, published as well as unpublished data on the multiple effects of exogenous adenosine and application of adenosine-related agents, performed using the arterially perfused cat eye, will be reviewed and discussed within the framework of the neuroprotective role of adenosine. The isolated, arterially perfused eye preparation has the advantage of combining integrity of the eye structure, exact control of arterial concentration and timing of applied pharmacological agents, and access to electrophysiological parameters of both retina and optic nerve, as well as the ability to control and monitor perfusate flow. The absence of red blood cells in the perfusate prevents adenosine from being metabolized prior to reaching the eye.