Integration of adult patients with phenylketonuria into professional life: long-term follow-up of 27 patients in a single centre in Switzerland

BACKGROUND Neonatal screening and treatment of phenylketonuria (PKU) prevent the development of neurocognitive impairment. The degree of dysfunction may be related to metabolic control and responsible for a hampered school career. METHODS This was a retrospective study from a single metabolic unit of a Swiss University Hospital. The time point of diagnosis and all Phenylalanin (Phe) concentrations during the follow-up were recorded. The primary outcome was integration into professional life defined as no professional studies versus accomplished apprenticeship versus high school diploma/university. Phe levels were correlated with professional outcome. The control group consisted of the patients' healthy parents and siblings. RESULTS A total of 27 patients (13 females, 14 males) were included in the study. The mean (SD) follow-up period was 25.1 (7.6) years. The control group consisted of 57 subjects. Overall, 23 patients were diagnosed by neonatal screening, and 4 patients were diagnosed later. All 4 were in the non-professional study group. Compared with the controls there were significantly more patients in the non-professional study group (26% vs 9%, p <0.05) and significantly less in the accomplished apprenticeship group (59% vs 82%; p <0.04). After exclusion of the patients with late diagnosis no significant differences were found with regard to the professional integration between patients and controls. Significant differences in Phe-levels between the three groups could be documented between 2-10 years of age with the highest levels in the non-professional study followed by the accomplished apprenticeship and the high school diploma group (p <0.01). CONCLUSION Patients who are diagnosed by neonatal screening and are consequently cared for are able to accomplish an apprenticeship or a high school diploma.

Automatic Segmentation of the Eye in 3D Magnetic Resonance Imaging: A novel Statistical Shape Model for treatment planning of Retinoblastoma

Purpose: Proper delineation of ocular anatomy in 3D imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic Resonance Imaging (MRI) is nowadays utilized in clinical practice for the diagnosis confirmation and treatment planning of retinoblastoma in infants, where it serves as a source of information, complementary to the Fundus or Ultrasound imaging. Here we present a framework to fully automatically segment the eye anatomy in the MRI based on 3D Active Shape Models (ASM), we validate the results and present a proof of concept to automatically segment pathological eyes. Material and Methods: Manual and automatic segmentation were performed on 24 images of healthy children eyes (3.29±2.15 years). Imaging was performed using a 3T MRI scanner. The ASM comprises the lens, the vitreous humor, the sclera and the cornea. The model was fitted by first automatically detecting the position of the eye center, the lens and the optic nerve, then aligning the model and fitting it to the patient. We validated our segmentation method using a leave-one-out cross validation. The segmentation results were evaluated by measuring the overlap using the Dice Similarity Coefficient (DSC) and the mean distance error. Results: We obtained a DSC of 94.90±2.12% for the sclera and the cornea, 94.72±1.89% for the vitreous humor and 85.16±4.91% for the lens. The mean distance error was 0.26±0.09mm. The entire process took 14s on average per eye. Conclusion: We provide a reliable and accurate tool that enables clinicians to automatically segment the sclera, the cornea, the vitreous humor and the lens using MRI. We additionally present a proof of concept for fully automatically segmenting pathological eyes. This tool reduces the time needed for eye shape delineation and thus can help clinicians when planning eye treatment and confirming the extent of the tumor.

Ophthalmic complications and local anesthesia. Pathophysiology and types of eye complications after intraoral dental anesthesia, and clinical recommendations

The present article reviews the different types of ophthalmologic complications following administration of intraoral local anesthesia. Since the first report by Brain in 1936, case reports about that topic have been published regularly in the literature. However, clinical studies evaluating the incidence of ophthalmologic complications after intraoral local anesthesia are rarely available. Previous data point to a frequency ranging from 0.03% to 0.13%. The most frequently described ophthalmologic complications include diplopia (double vision), ptosis (drooping of upper eyelid), and mydriasis (dilatation of pupil). Disorders that rather affect periorbital structures than the eye directly include facial paralysis and periorbital blanching (angiospasm). Diverse pathophysiologic mechanisms and causes have been reported in the literature, with the inadvertent intravascular administration of the local anesthetic considered the primary reason. The agent as well as the vasopressor is transported retrogradely via arteries or veins to the orbit or to periorbital structures (such as the cavernous sinus) with subsequent anesthesia of nerves and paralysis of muscles distant from the oral cavity. In general the ophthalmologic complications begin shortly after administration of the local anesthesia, and disappear once the local anesthesia has subsided.

The role of the right frontal eye field in overt visual attention deployment as assessed by free visual exploration

The frontal eye field (FEF) is known to be involved in saccade generation and visual attention control. Studies applying covert attentional orienting paradigms have shown that the right FEF is involved in attentional shifts to both the left and the right hemifield. In the current study, we aimed at examining the effects of inhibitory continuous theta burst (cTBS) transcranial magnetic stimulation over the right FEF on overt attentional orienting, as measured by a free visual exploration paradigm. In forty-two healthy subjects, free visual exploration of naturalistic pictures was tested in three conditions: (1) after cTBS over the right FEF; (2) after cTBS over a control site (vertex); and, (3) without any stimulation. The results showed that cTBS over the right FEF-but not cTBS over the vertex-triggered significant changes in the spatial distribution of the cumulative fixation duration. Compared to the group without stimulation and the group with cTBS over the vertex, cTBS over the right FEF decreased cumulative fixation duration in the left and in the right peripheral regions, and increased cumulative fixation duration in the central region. The present study supports the view that the right FEF is involved in the bilateral control of not only covert, but also of overt, peripheral visual attention.

Acute onset incomitant image disparity modifies saccadic and vergence eye movements.

New-onset impairment of ocular motility will cause incomitant strabismus, i.e., a gaze-dependent ocular misalignment. This ocular misalignment will cause retinal disparity, that is, a deviation of the spatial position of an image on the retina of both eyes, which is a trigger for a vergence eye movement that results in ocular realignment. If the vergence movement fails, the eyes remain misaligned, resulting in double vision. Adaptive processes to such incomitant vergence stimuli are poorly understood. In this study, we have investigated the physiological oculomotor response of saccadic and vergence eye movements in healthy individuals after shifting gaze from a viewing position without image disparity into a field of view with increased image disparity, thus in conditions mimicking incomitance. Repetitive saccadic eye movements into a visual field with increased stimulus disparity lead to a rapid modification of the oculomotor response: (a) Saccades showed immediate disconjugacy (p < 0.001) resulting in decreased retinal image disparity at the end of a saccade. (b) Vergence kinetics improved over time (p < 0.001). This modified oculomotor response enables a more prompt restoration of ocular alignment in new-onset incomitance.

Fusion of fundus images and MRI data of the human eye

Purpose Ophthalmologists are confronted with a set of different image modalities to diagnose eye tumors e.g., fundus photography, CT and MRI. However, these images are often complementary and represent pathologies differently. Some aspects of tumors can only be seen in a particular modality. A fusion of modalities would improve the contextual information for diagnosis. The presented work attempts to register color fundus photography with MRI volumes. This would complement the low resolution 3D information in the MRI with high resolution 2D fundus images. Methods MRI volumes were acquired from 12 infants under the age of 5 with unilateral retinoblastoma. The contrast-enhanced T1-FLAIR sequence was performed with an isotropic resolution of less than 0.5mm. Fundus images were acquired with a RetCam camera. For healthy eyes, two landmarks were used: the optic disk and the fovea. The eyes were detected and extracted from the MRI volume using a 3D adaption of the Fast Radial Symmetry Transform (FRST). The cropped volume was automatically segmented using the Split Bregman algorithm. The optic nerve was enhanced by a Frangi vessel filter. By intersection the nerve with the retina the optic disk was found. The fovea position was estimated by constraining the position with the angle between the optic and the visual axis as well as the distance from the optic disk. The optical axis was detected automatically by fitting a parable on to the lens surface. On the fundus, the optic disk and the fovea were detected by using the method of Budai et al. Finally, the image was projected on to the segmented surface using the lens position as the camera center. In tumor affected eyes, the manually segmented tumors were used instead of the optic disk and macula for the registration. Results In all of the 12 MRI volumes that were tested the 24 eyes were found correctly, including healthy and pathological cases. In healthy eyes the optic nerve head was found in all of the tested eyes with an error of 1.08 +/- 0.37mm. A successful registration can be seen in figure 1. Conclusions The presented method is a step toward automatic fusion of modalities in ophthalmology. The combination enhances the MRI volume with higher resolution from the color fundus on the retina. Tumor treatment planning is improved by avoiding critical structures and disease progression monitoring is made easier.

Ego depletion and attention regulation under pressure: Is a temporary loss of self-control strength indeed related to impaired attention regulation?

In the present study we investigated whether ego depletion negatively affects attention regulation under pressure in sports by assessing participants’ dart throwing performance and accompanying gaze behavior. According to the strength model of self-control the most important aspect of self-control is attention regulation (Schmeichel & Baumeister, 2010). As higher levels of state anxiety are associated with impaired attention regulation (Nieuwenhuys & Oudejans, 2012) we chose a mixed design with ego depletion (yes vs. no) as between-subjects and anxiety level (high vs. low) as within-subjects factor. A total of 28 right-handed students participated in our study (Mage = 23.4, SDage = 2.5; 10 female; no professional dart experience). Participants performed a perceptual-motor task requiring selective attention, namely, dart throwing. The task was performed while participants were positioned high and low on a climbing wall (i.e., with high and low levels of anxiety). In line with our expectations, a mixed-design ANOVA revealed that depleted participants in the high anxiety condition performed worse (p < .001) and displayed a shorter final fixation on bull’s eye (p < .01) than in the low anxiety condition, demonstrating that when one is depleted attention regulation under pressure cannot be maintained. This is the first study that directly supports the general assumption that ego depletion is a major factor in influencing attention regulation under pressure.

The Quiet Eye in Motor Performance and Learning – Functional and Theoretical Considerations

High precision in motor skill performance, in both sport and other domains (e.g. surgery and aviation), requires the efficient coupling of perceptual inputs (e.g. vision) and motor actions. A particular gaze strategy, which has received much attention within the literature, has been shown to predict both inter- (expert vs. novice) and intra-individual (successful vs. unsuccessful) motor performance (see Vine et al., 2014). Vickers (1996) labelled this phenomenon the quiet eye (QE) which is defined as the final fixation before the initiation of the crucial phase of movement. While the positive influence of a long QE on accuracy has been revealed in a range of different motor skills, there is a growing number of studies suggesting that the relationship between QE and motor performance is not entirely monotonic. This raises interesting questions regarding the QE’s purview, and the theoretical approaches explaining its functionality. This talk aims to present an overview of the issues described above, and to discuss contemporary research and experimental approaches to examining the QE phenomenon. In the first part of the talk Dr. Vine will provide a brief and critical review of the literature, highlighting recent empirical advancements and potential directions for future research. In the second part, Dr. Klostermann will communicate three different theoretical approaches to explain the relationship between QE and motor performance. Drawing upon aspects of all three of these theoretical approaches, a functional inhibition role for the QE (related to movement parameterisation) will be proposed.

Cue Recognition and Integration - Eye Tracking Evidence of Processing Differences in Sentence Comprehension in Aphasia

PURPOSE: We aimed at further elucidating whether aphasic patients' difficulties in understanding non-canonical sentence structures, such as Passive or Object-Verb-Subject sentences, can be attributed to impaired morphosyntactic cue recognition, and to problems in integrating competing interpretations. METHODS: A sentence-picture matching task with canonical and non-canonical spoken sentences was performed using concurrent eye tracking. Accuracy, reaction time, and eye tracking data (fixations) of 50 healthy subjects and 12 aphasic patients were analysed. RESULTS: Patients showed increased error rates and reaction times, as well as delayed fixation preferences for target pictures in non-canonical sentences. Patients' fixation patterns differed from healthy controls and revealed deficits in recognizing and immediately integrating morphosyntactic cues. CONCLUSION: Our study corroborates the notion that difficulties in understanding syntactically complex sentences are attributable to a processing deficit encompassing delayed and therefore impaired recognition and integration of cues, as well as increased competition between interpretations.

Incidence and causative agents of chemical eye injuries in Switzerland

CONTEXT Chemical eye injuries are ophthalmological emergencies with a high risk of secondary complications and severe visual loss. Only limited epidemiological data for such injuries are available for many countries. PATIENTS AND METHODS We performed two independent studies. The cause of chemical eye injuries was assessed with a prospective questionnaire study. Questionnaires were sent to all ophthalmologists in Switzerland. A total of 163 patients (205 eyes) were included, between December 2012 and October 2014. Independent of the questionnaire study, the incidence of chemical eye injuries was assessed with a retrospective cohort study design using the database of the mandatory accident insurance. RESULTS Ophthalmological questionnaires revealed that plaster/cement (20.5%), alkaline (12.2%) and acid (10.2%) solutions caused the highest number of chemical injuries. Only 2% of all injuries were classified as grade III and none as grade IV (Roper-Hall classification). The official toxicological information phone-hotline was contacted in 4.3% of cases. Using data from the accident insurance, an incidence of chemical eye injuries of about 50/100 000/year was found in the working population. CONCLUSION Here, we present data on the involved agents of chemical eye injuries in Switzerland, and also the incidence of such injuries in the working population. This may also help to assess the need for further education programs and to improve and direct preventive measures.

Street crossing behavior in younger and older pedestrians: an eye- and head-tracking study

BACKGROUND: Crossing a street can be a very difficult task for older pedestrians. With increased age and potential cognitive decline, older people take the decision to cross a street primarily based on vehicles' distance, and not on their speed. Furthermore, older pedestrians tend to overestimate their own walking speed, and could not adapt it according to the traffic conditions. Pedestrians' behavior is often tested using virtual reality. Virtual reality presents the advantage of being safe, cost-effective, and allows using standardized test conditions. METHODS: This paper describes an observational study with older and younger adults. Street crossing behavior was investigated in 18 healthy, younger and 18 older subjects by using a virtual reality setting. The aim of the study was to measure behavioral data (such as eye and head movements) and to assess how the two age groups differ in terms of number of safe street crossings, virtual crashes, and missed street crossing opportunities. Street crossing behavior, eye and head movements, in older and younger subjects, were compared with non-parametric tests. RESULTS: The results showed that younger pedestrians behaved in a more secure manner while crossing a street, as compared to older people. The eye and head movements analysis revealed that older people looked more at the ground and less at the other side of the street to cross. CONCLUSIONS: The less secure behavior in street crossing found in older pedestrians could be explained by their reduced cognitive and visual abilities, which, in turn, resulted in difficulties in the decision-making process, especially under time pressure. Decisions to cross a street are based on the distance of the oncoming cars, rather than their speed, for both groups. Older pedestrians look more at their feet, probably because of their need of more time to plan precise stepping movement and, in turn, pay less attention to the traffic. This might help to set up guidelines for improving senior pedestrians' safety, in terms of speed limits, road design, and mixed physical-cognitive trainings.

Comprehension of Co-Speech Gestures in Aphasic Patients: An Eye Movement Study.

BACKGROUND: Co-speech gestures are omnipresent and a crucial element of human interaction by facilitating language comprehension. However, it is unclear whether gestures also support language comprehension in aphasic patients. Using visual exploration behavior analysis, the present study aimed to investigate the influence of congruence between speech and co-speech gestures on comprehension in terms of accuracy in a decision task. METHOD: Twenty aphasic patients and 30 healthy controls watched videos in which speech was either combined with meaningless (baseline condition), congruent, or incongruent gestures. Comprehension was assessed with a decision task, while remote eye-tracking allowed analysis of visual exploration. RESULTS: In aphasic patients, the incongruent condition resulted in a significant decrease of accuracy, while the congruent condition led to a significant increase in accuracy compared to baseline accuracy. In the control group, the incongruent condition resulted in a decrease in accuracy, while the congruent condition did not significantly increase the accuracy. Visual exploration analysis showed that patients fixated significantly less on the face and tended to fixate more on the gesturing hands compared to controls. CONCLUSION: Co-speech gestures play an important role for aphasic patients as they modulate comprehension. Incongruent gestures evoke significant interference and deteriorate patients' comprehension. In contrast, congruent gestures enhance comprehension in aphasic patients, which might be valuable for clinical and therapeutic purposes.

Left atrial remodeling, early repolarization pattern, and inflammatory cytokines in professional soccer players

OBJECTIVES: Although regular physical exercise clearly reduces cardiovascular morbidity risk, long-term endurance sports practice has been recognized as a risk factor for atrial fibrillation (AF). However, the mechanisms how endurance sports can lead to AF are not yet clear. The aim of our present study was to investigate the influence of long-term endurance training on vagal tone, atrial size, and inflammatory profile in professional elite soccer players. METHODS: A total of 25 professional major league soccer players (mean age 24+/-4 years) and 20 sedentary controls (mean age 26+/-3 years) were included in the study and consecutively examined. All subjects underwent a sports cardiology check-up with physical examination, electrocardiography, echocardiography, exercise testing on a bicycle ergometer, and laboratory analysis [standard laboratory and cytokine profile: interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-8, IL-10]. RESULTS: Athletes were divided into two groups according to presence or absence of an early repolarization (ER) pattern, defined as a ST-segment elevation at the J-point (STE) >/=0.1mm in 2 leads. Athletes with an ER pattern showed significantly lower heart rate and an increased E/e' ratio compared to athletes without an ER pattern. STE significantly correlated with E/e' ratio as well as with left atrial (LA) volume. The pro-inflammatory cytokines IL-6, IL-8, TNF-alpha as well as the anti-inflammatory cytokine IL-10 were significantly elevated in all soccer players. However, athletes with an ER pattern had significantly higher IL-6 plasma levels than athletes without ER pattern. Furthermore, athletes with "high" level IL-6 had significantly larger LA volumes than players with "low" level IL-6. CONCLUSIONS: Athletes with an ER pattern had significantly higher E/e' ratios, reflecting higher atrial filling pressures, higher LA volume, and higher IL-6 plasma levels. All these factors may contribute to atrial remodeling over time and thus increase the risk of AF in long-term endurance sports.

Disrupting frontal eye-field activity impairs memory recall

A large body of research demonstrated that participants preferably look back to the encoding location when retrieving visual information from memory. However, the role of this 'looking back to nothing' is still debated. The goal of the present study was to extend this line of research by examining whether an important area in the cortical representation of the oculomotor system, the frontal eye field (FEF), is involved in memory retrieval. To interfere with the activity of the FEF, we used inhibitory continuous theta burst stimulation (cTBS). Before stimulation was applied, participants encoded a complex scene and performed a short-term (immediately after encoding) or long-term (after 24 h) recall task, just after cTBS over the right FEF or sham stimulation. cTBS did not affect overall performance, but stimulation and statement type (object vs. location) interacted. cTBS over the right FEF tended to impair object recall sensitivity, whereas there was no effect on location recall sensitivity. These findings suggest that the FEF is involved in retrieving object information from scene memory, supporting the hypothesis that the oculomotor system contributes to memory recall.