White eye phenotypes and their genetic analysis

An interesting case for undergraduate students of general Genetics is to consider that different genes can produce the same or similar phenotypes. We present here an experiment to discover that the same phenotype could be produced by different genes, and then, to carry out the genetic analysis of these genes. For this laboratory study we have used the following Drosophila melanogaster strains: white (white eyes) and scarlet-brown (white eyes).

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 3-dimensional (3D) imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic resonance imaging (MRI) is presently used in clinical practice for diagnosis confirmation and treatment planning for treatment of retinoblastoma in infants, where it serves as a source of information, complementary to the fundus or ultrasonographic imaging. Here we present a framework to fully automatically segment the eye anatomy for MRI based on 3D active shape models (ASM), and we validate the results and present a proof of concept to automatically segment pathological eyes. METHODS AND MATERIALS: Manual and automatic segmentation were performed in 24 images of healthy children's eyes (3.29 ± 2.15 years of age). Imaging was performed using a 3-T MRI scanner. The ASM consists of 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, and then aligning the model and fitting it to the patient. We validated our segmentation method by 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 ± 0.09 mm. The entire process took 14 seconds 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 eye pathology. 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.

Very long-term follow-up after percutaneous closure of patent foramen ovale.

AIMS: To evaluate the very long-term risk of recurrent thromboembolic events in patients treated by percutaneous PFO closure. METHODS AND RESULTS: Between 1998 and 2008, a total of 232 consecutive patients with PFO and a high suspicion of paradoxical embolism were treated by percutaneous closure. The following major events were observed during hospitalisation: implantation failure (one patient) and appearance of an acute left-sided device thrombus requiring surgery (one patient). The primary endpoint of the study was a recurrent embolic event beyond at least five years' follow-up. During a mean follow-up of 7.6±2.4 years, this event occurred in five patients, representing a 0.28% annual/patient risk. Other major complications during follow-up were the following: late thrombus formation on the device (two patients) and transient atrial fibrillation (15 patients). Three patients died during follow-up from cardiovascular causes considered not related to the index procedure. The PFO was judged closed on follow-up echocardiography in 92.3% of patients. CONCLUSIONS: Long-term follow-up following percutaneous PFO closure for presumed paradoxical embolism reveals very low recurrence rates. This observation should be put in perspective with recent published randomised trials comparing percutaneous closure and medical therapy.

Abrogation of HMX1 function causes rare oculoauricular syndrome associated with congenital cataract, anterior segment dysgenesis, and retinal dystrophy.

PURPOSE: To define the phenotypic manifestation, confirm the genetic basis, and delineate the pathogenic mechanisms underlying an oculoauricular syndrome (OAS). METHODS: Two individuals from a consanguineous family underwent comprehensive clinical phenotyping and electrodiagnostic testing (EDT). Genome-wide microarray analysis and Sanger sequencing of the candidate gene were used to identify the likely causal variant. Protein modelling, Western blotting, and dual luciferase assays were used to assess the pathogenic effect of the variant in vitro. RESULTS: Complex developmental ocular abnormalities of congenital cataract, anterior segment dysgenesis, iris coloboma, early-onset retinal dystrophy, and abnormal external ear cartilage presented in the affected family members. Genetic analyses identified a homozygous c.650A>C; p.(Gln217Pro) missense mutation within the highly conserved homeodomain of the H6 family homeobox 1 (HMX1) gene. Protein modelling predicts that the variant may have a detrimental effect on protein folding and/or stability. In vitro analyses were able to demonstrate that the mutation has no effect on protein expression but adversely alters function. CONCLUSIONS: Oculoauricular syndrome is an autosomal recessive condition that has a profound effect on the development of the external ear, anterior segment, and retina, leading to significant visual loss at an early age. This study has delineated the phenotype and confirmed HMX1 as the gene causative of OAS, enabling the description of only the second family with the condition. HMX1 is a key player in ocular development, possibly in both the pathway responsible for lens and retina development, and via the gene network integral to optic fissure closure.

Labor market experience and well-being after firm closure. Survey evidence on displaced manufacturing workers in Switzerland

This study examines how plant closure affected individuals' careers and lives about two years after they lost their job. We analyze the displaced workers' reemployment prospects and study for reemployed workers the characteristics of their new jobs in terms of reemployment sectors, wages, and job quality. Additionally, we inquire how workers' sociability and subjective well-being were affected by job loss. Our analysis is based on our own survey conducted in Switzerland in 2011. The survey included the workforce of five manufacturing companies that had closed down two years earlier. We addressed the risk of biases typically prevailing with observational data by complementing it with register data from the public unemployment insurance. Moreover, we use a control group based on matched data from the Swiss Household Panel. We find that workers experience strongly diverging outcomes after plant closure: on the one hand, high proportions of the workers experience a smooth transition after plant closure. More than two-thirds of the workers returned to employment, more than half of them within less than six months. With respect to their social lives, we find that positive changes in relationships with their spouse, family and friends are more frequent than negative changes. On the other hand, for a small group of workers plant closure had a detrimental effect. Close to twenty percent remained unemployed. About ten percent of the workers were long-term unemployed and subsequently often were reemployed in jobs of lower quality. Unemployed workers and workers who dropped out of the labor force were particularly prone to find their subjective well-being decreasing. The most vulnerable subgroup in our study were workers over 55. This result stands in striking contrast to a large body of literature that considers labor market institutions to be primarily biased against young workers. Our findings show that older workers not only take longer to find a job but are also less likely to return to employment. Moreover, if they manage to find a job, they experience the severest cuts in wages and job quality of all cohorts. From a life-course perspective this result is remarkable since it shows that workers are not protected from hardship in their late careers. In light of the current demographic changes this finding may have important policy implications. -- Cette étude analyse l'impact des fermetures d'entreprises sur les travailleurs licenciés. Plus précisément, nous examinons les chances de réinsertion des travailleurs dans le marché du travail et - pour ceux qui l'ont fait avec succès - dans quels secteurs, pour quels salaires et avec quelle qualité d'emploi ils sont réengagés. Nous nous intéressons également aux répercussions engendrées par la perte de l'emploi sur la sociabilité et le bien-être subjectif des travailleurs concernés. Notre analyse se base sur les données d'une enquête que nous avons menée en 2011. Cette enquête cible le personnel de cinq entreprises industrielles suisses qui avaient fermé leurs portes deux ans auparavant. Pour dépasser les biais typiques liés aux données d'observation, nous utilisons en complément des données administratives issues de l'assurance chômage publique. De plus, nous utilisons un groupe de contrôle basé sur des données appariées provenant du Panel Suisse de Ménage. Nos analyses montrent des résultats fortement contrastés. D'un côté, la majeure partie des travailleurs ont vécu une transition professionnelle plutôt facile : plus des deux tiers des personnes ont retrouvé un travail et parmi elles plus de la moitié en moins de six mois. Par rapport aux relations sociales, tant avec leur partenaire, qu'avec les membres de leur famille et leurs amis, les changements expérimentés étaient plus fréquemment positifs que négatifs. De l'autre côté, cependant, pour une petite partie de travailleurs la fermeture de leur entreprise a eu des conséquences très négatives sur leur carrière et leur bien-être. Au moment de notre enquête, presque vingt pourcents des travailleurs étaient au chômage. Les personnes au chômage et celles qui avaient quitté le marché du travail ont été particulièrement affectées par une diminution de leur bien-être subjectif. Les plus vulnérables parmi les travailleurs licenciés étaient ceux qui étaient âgés de plus de 55 ans. Notre analyse montre que les travailleurs âgés ont beaucoup moins fréquemment retrouvé un travail. Pour les personnes de plus de 55 ans qui ont tout de même retrouvé un emploi, la réinsertion a durée plus longtemps, les pertes de salaire étaient plus conséquentes et la diminution de la qualité de l'emploi plus grande que pour les autres cohortes. Au vu des changements démographiques actuels, ce résultat interpellant peut avoir des implications politiques importantes.

Eye-tracking of nodule detection in lung CT volumetric data.

PURPOSE: Signal detection on 3D medical images depends on many factors, such as foveal and peripheral vision, the type of signal, and background complexity, and the speed at which the frames are displayed. In this paper, the authors focus on the speed with which radiologists and naïve observers search through medical images. Prior to the study, the authors asked the radiologists to estimate the speed at which they scrolled through CT sets. They gave a subjective estimate of 5 frames per second (fps). The aim of this paper is to measure and analyze the speed with which humans scroll through image stacks, showing a method to visually display the behavior of observers as the search is made as well as measuring the accuracy of the decisions. This information will be useful in the development of model observers, mathematical algorithms that can be used to evaluate diagnostic imaging systems. METHODS: The authors performed a series of 3D 4-alternative forced-choice lung nodule detection tasks on volumetric stacks of chest CT images iteratively reconstructed in lung algorithm. The strategy used by three radiologists and three naïve observers was assessed using an eye-tracker in order to establish where their gaze was fixed during the experiment and to verify that when a decision was made, a correct answer was not due only to chance. In a first set of experiments, the observers were restricted to read the images at three fixed speeds of image scrolling and were allowed to see each alternative once. In the second set of experiments, the subjects were allowed to scroll through the image stacks at will with no time or gaze limits. In both static-speed and free-scrolling conditions, the four image stacks were displayed simultaneously. All trials were shown at two different image contrasts. RESULTS: The authors were able to determine a histogram of scrolling speeds in frames per second. The scrolling speed of the naïve observers and the radiologists at the moment the signal was detected was measured at 25-30 fps. For the task chosen, the performance of the observers was not affected by the contrast or experience of the observer. However, the naïve observers exhibited a different pattern of scrolling than the radiologists, which included a tendency toward higher number of direction changes and number of slices viewed. CONCLUSIONS: The authors have determined a distribution of speeds for volumetric detection tasks. The speed at detection was higher than that subjectively estimated by the radiologists before the experiment. The speed information that was measured will be useful in the development of 3D model observers, especially anthropomorphic model observers which try to mimic human behavior.

Apical closure device for transapical valve procedures?.

OBJECTIVES: Transapical transcatheter valve procedures are performed through a left minithoracotomy and require apical sutures to seal the apical access site. The use of large-calibre devices compromises any attempt to fully perform the procedure with a thoracoscopic approach or percutaneously. We report our preliminary experience in animals with a new sutureless self-expandable apical occluder, engineered to perform transapical access site closure in a minimally invasive setting with large-size introducer sheaths. METHODS: The apical occluder with extendable waist was implanted in six young pigs during an acute animal study. Under general anaesthesia, animals (mean weight: 62 ± 8 kg) received full heparinization (heparin: 100 UI/kg; activated clotting time above 250 s). Through a median sternotomy, a 21-Fr Certitude? introducer sheath (outer diameter: 25 Fr) was placed over the wire into the cardiac apex. The delivery catheter carrying the constrained apical plug was inserted into the sheath and deployed under fluoroscopic control, whereas the Certitude? was retrieved. After protamine infusion, we observed and recorded the 1-h bleeding with standard haemodynamic parameters. Animals were sacrificed, and hearts analysed. RESULTS: Six apical closure devices were successfully introduced and deployed in six pig hearts through large-size apical sheaths at first attempt. In all animals, the plugs guaranteed immediate apical sealing and traces of blood were collected in the pericardium during the 1-h observational period (mean of 16 ± 3.4 ml of blood loss per animal). Haemodynamic parameters remained stable during the entire study period and no plug dislodgement was detected with normal systemic blood pressure (mean arterial mean blood pressure: 65 ± 7 mmHg). Post-mortem analysis confirmed the full deployment and good fixation of all plugs, without macroscopic damages to the surrounding myocardium. CONCLUSIONS: This sutureless self-expandable apical occluder is a simple device capable of sealing large-size apical access sites (20-35 Fr) in an acute animal study. This approach is a step further towards less invasive transapical valve procedures in the clinical setting, and further animal tests will be performed to confirm the long-term efficacy and safety of this device.

Eye lens monitoring for interventional radiology personnel: dosemeters, calibration and practical aspects of H p (3) monitoring. A 2015 review.

A thorough literature review about the current situation on the implementation of eye lens monitoring has been performed in order to provide recommendations regarding dosemeter types, calibration procedures and practical aspects of eye lens monitoring for interventional radiology personnel. Most relevant data and recommendations from about 100 papers have been analysed and classified in the following topics: challenges of today in eye lens monitoring; conversion coefficients, phantoms and calibration procedures for eye lens dose evaluation; correction factors and dosemeters for eye lens dose measurements; dosemeter position and influence of protective devices. The major findings of the review can be summarised as follows: the recommended operational quantity for the eye lens monitoring is H p (3). At present, several dosemeters are available for eye lens monitoring and calibration procedures are being developed. However, in practice, very often, alternative methods are used to assess the dose to the eye lens. A summary of correction factors found in the literature for the assessment of the eye lens dose is provided. These factors can give an estimation of the eye lens dose when alternative methods, such as the use of a whole body dosemeter, are used. A wide range of values is found, thus indicating the large uncertainty associated with these simplified methods. Reduction factors from most common protective devices obtained experimentally and using Monte Carlo calculations are presented. The paper concludes that the use of a dosemeter placed at collar level outside the lead apron can provide a useful first estimate of the eye lens exposure. However, for workplaces with estimated annual equivalent dose to the eye lens close to the dose limit, specific eye lens monitoring should be performed. Finally, training of the involved medical staff on the risks of ionising radiation for the eye lens and on the correct use of protective systems is strongly recommended.

A role of Eye Vergence in Covert Attention

Covert spatial attention produces biases in perceptual and neural responses in the absence of overt orienting movements. The neural mechanism that gives rise to these effects is poorly understood. Here we report the relation between fixational eye movements, namely eye vergence, and covert attention. Visual stimuli modulate the angle of eye vergence as a function of their ability to capture attention. This illustrates the relation between eye vergence and bottom-up attention. In visual and auditory cue/no-cue paradigms, the angle of vergence is greater in the cue condition than in the no-cue condition. This shows a top-down attention component. In conclusion, observations reveal a close link between covert attention and modulation in eye vergence during eye fixation. Our study suggests a basis for the use of eye vergence as a tool for measuring attention and may provide new insights into attention and perceptual disorders.

Use of a ventricular septal defect occluder for apical closure in transapical aortic valve replacement.

During transapical transcatheter aortic valve replacement (TA-TAVR), the apical closure remains a challenge for the surgeon, having the risk for ventricular tear and massive bleeding. Apical closure devices are already under clinical evaluation, but only a few can lead to a full percutaneous TA-TAVR. We describe the successful use of a 9-mm myocardial occluder (ventricular septal defect occluder) that was used to seal the apex after a standard TA-TAVR (using the Sapien XT 23-mm transcatheter valve and the Ascendra + delivery system). The placement of the nonmodified myocardial occluder was performed through the Ascendra + delivery system, with a very small amount of blood loss and an acceptable sealing of the apical tear. This approach is feasible and represents a further step toward true-percutaneous transapical heart valve procedures. Modified apical occluders are under evaluation in animal models.

Apical access and closure devices for transapical transcatheter heart valve procedures.

The majority of transcatheter aortic valve implantations, structural heart procedures and the newly developed transcatheter mitral valve repair and replacement are traditionally performed either through a transfemoral or a transapical access site, depending on the presence of severe peripheral vascular disease or anatomic limitations. The transapical approach, which carries specific advantages related to its antegrade nature and the short distance between the introduction site and the cardiac target, is traditionally performed through a left anterolateral mini-thoracotomy and requires rib retractors, soft tissue retractors and reinforced apical sutures to secure, at first, the left ventricular apex for the introduction of the stent-valve delivery systems and then to seal the access site at the end of the procedure. However, despite the advent of low-profile apical sheaths and newly designed delivery systems, the apical approach represents a challenge for the surgeon, as it has the risk of apical tear, life-threatening apical bleeding, myocardial damage, coronary damage and infections. Last but not least, the use of large-calibre stent-valve delivery systems and devices through standard mini-thoracotomies compromises any attempt to perform transapical transcatheter structural heart procedures entirely percutaneously, as happens with the transfemoral access site, or via a thoracoscopic or a miniaturised video-assisted percutaneous technique. During the past few years, prototypes of apical access and closure devices for transapical heart valve procedures have been developed and tested to make this standardised successful procedure easier. Some of them represent an important step towards the development of truly percutaneous transcatheter transapical heart valve procedures in the clinical setting.

Eye Fundus Image Analysis for Automatic Detection of Diabetic Retinopathy

Diabetes is a rapidly increasing worldwide problem which is characterised by defective metabolism of glucose that causes long-term dysfunction and failure of various organs. The most common complication of diabetes is diabetic retinopathy (DR), which is one of the primary causes of blindness and visual impairment in adults. The rapid increase of diabetes pushes the limits of the current DR screening capabilities for which the digital imaging of the eye fundus (retinal imaging), and automatic or semi-automatic image analysis algorithms provide a potential solution. In this work, the use of colour in the detection of diabetic retinopathy is statistically studied using a supervised algorithm based on one-class classification and Gaussian mixture model estimation. The presented algorithm distinguishes a certain diabetic lesion type from all other possible objects in eye fundus images by only estimating the probability density function of that certain lesion type. For the training and ground truth estimation, the algorithm combines manual annotations of several experts for which the best practices were experimentally selected. By assessing the algorithm’s performance while conducting experiments with the colour space selection, both illuminance and colour correction, and background class information, the use of colour in the detection of diabetic retinopathy was quantitatively evaluated. Another contribution of this work is the benchmarking framework for eye fundus image analysis algorithms needed for the development of the automatic DR detection algorithms. The benchmarking framework provides guidelines on how to construct a benchmarking database that comprises true patient images, ground truth, and an evaluation protocol. The evaluation is based on the standard receiver operating characteristics analysis and it follows the medical practice in the decision making providing protocols for image- and pixel-based evaluations. During the work, two public medical image databases with ground truth were published: DIARETDB0 and DIARETDB1. The framework, DR databases and the final algorithm, are made public in the web to set the baseline results for automatic detection of diabetic retinopathy. Although deviating from the general context of the thesis, a simple and effective optic disc localisation method is presented. The optic disc localisation is discussed, since normal eye fundus structures are fundamental in the characterisation of DR.

A Tomada de Decisão (Bio)ética: Estudo Preliminar Utilizando o Mobile Eye Tracking

RESUMO A tomada de decisão é uma das dimensões essenciais da formação do profissional da saúde, como mencionado nas atuais Diretrizes Curriculares Nacionais do Curso de Graduação em Medicina. O processo decisório, no âmbito da saúde, envolve diferentes aspectos, incluindo os elementos (bio)éticos. Nesse sentido, pesquisas que investiguem a tomada de decisão em (bio)ética poderão elucidar passos ainda não completamente esclarecidos, permitindo uma construção mais efetiva das competências em (bio)ética, na graduação e na pós-graduação. Diante desta perspectiva, o objetivo deste estudo é explorar possibilidades de uso do Mobile Eye Tracking para o estudo do papel da atenção visual – durante a exibição de filmes de cinema – no processo decisório em (bio)ética.