Nasal surgery in patients with systemic disorders

Multisystemic disorders represent a heterogenous group of diseases which can primarily manifest at the nose and paranasal sinuses as limited disease or secondarily as part of systemic involvement. Rhinologists therefore play an important role in the diagnostic but also therapeutic process. Although therapy of multisystemic disorders is primary systemic, additional rhinosurgery may become necessary. The spectrum of procedures consists of sinus surgery, surgery of the orbit and lacrimal duct, septorhinoplasty and closure of nasal septal perforation. Since the prevalence of most systemic diseases is very rare, recommendations are based on the analysis of single case reports and case series with a limited number of patients only. Although data is still limited, experiences published so far have shown that autologous cartilage or bone grafts can be used in nasal reconstruction of deformities caused by tuberculosis, leprosy, Wegener’s granulomatosis, sarcoidosis and relapsing polychondritis. Experiences gained from these diseases support the concept that well-established techniques of septorhinoplasty can be used in systemic diseases as well. However, a state of remission is an essential condition before considering any rhinosurgery in these patients. Even under these circumstances revision surgery has to be expected more frequently compared to the typical collective of patients undergoing septorhinoplasty. In addition, experiences gained from saddle nose reconstruction may in part be of value for the treatment of nasal septal perforations since implantation of cartilage grafts often represents an essential step in multilayer techniques of closure of nasal septal perforations. Aside from the treatment of orbital complications sinus surgery has been proven beneficial in reducing nasal symptoms and increasing quality of life in patients refractory to systemic treatment

Validation of mobile eye-tracking as novel and efficient means for differentiating progressive supranuclear palsy from Parkinson's disease

Background: The decreased ability to carry out vertical saccades is a key symptom of Progressive Supranuclear Palsy (PSP). Objective measurement devices can help to reliably detect subtle eye movement disturbances to improve sensitivity and specificity of the clinical diagnosis. The present study aims at transferring findings from restricted stationary video-oculography (VOG) to a wearable head-mounted device, which can be readily applied in clinical practice. Methods: We investigated the eye movements in 10 possible or probable PSP patients, 11 Parkinson's disease (PD) patients, and 10 age-matched healthy controls (HCs) using a mobile, gaze-driven video camera setup (EyeSeeCam). Ocular movements were analyzed during a standardized fixation protocol and in an unrestricted real-life scenario while walking along a corridor. Results: The EyeSeeCam detected prominent impairment of both saccade velocity and amplitude in PSP patients, differentiating them from PD and HCs. Differences were particularly evident for saccades in the vertical plane, and stronger for saccades than for other eye movements. Differences were more pronounced during the standardized protocol than in the real-life scenario. Conclusions: Combined analysis of saccade velocity and saccade amplitude during the fixation protocol with the EyeSeeCam provides a simple, rapid (<20 s), and reliable tool to differentiate clinically established PSP patients from PD and HCs. As such, our findings prepare the ground for using wearable eye-tracking in patients with uncertain diagnoses

Gaze-Driven approach for estimating luminance values in the field of view for discomfort assessments

A gaze-driven methodology for discomfort glare was developed and applied for glare evaluation. A series of user assessments were performed in an office-like test laboratory under various lighting conditions. The participants’ gaze responses were recorded by means of mobile eye tracking while monitoring photometric quantities relevant to visual comfort using HDR luminance imaging. The integration of the luminance images coupled with eye-tracking methods enabled us to use gaze-centred luminance distribution to have an accurate estimate of the light received at the eye. Using a novel gaze-driven approach, a unique database was created as a basis to investigate the gaze direction dependencies of visual comfort. Here we compare the proposed gaze-driven approach with two other approaches based on fixed-gaze assumptions: gaze fixating on the task area, and gaze shifted 45 ° towards the window area. The results show that there is a significant difference between luminance distributions driven by gaze and those based on fixed-gaze assumptions, indicating a potentially important impact on glare assessment results as well

Zn2+-triggered self-assembly of Gonadorelin [6-D-Phe] to produce nanostructures and fibrils

A synthetic derivative, GnRH [6-D-Phe], stable against enzymatic degradation, self-assembles and forms nanostructures and fibrils upon a pH shift in the presence of different concentrations of Zn2+ in vitro. Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR) revealed the existence of higher order assembly of Zn2+: GnRH [6-D-Phe]. Nuclear Magnetic Resonance spectroscopy (NMR) indicated a weak interaction between Zn2+ and GnRH [6-D-Phe]. Atomic Force Microscopy (AFM) showed the existence of GnRH [6-D-Phe] oligomers and fibrils. Molecular Dynamic (MD) simulation of the 10: 1 Zn2+: GnRH [6-D-Phe] explored the interaction and dimerization processes. In contrast to already existing short peptide fibrils, GnRH [6-D-Phe] nanostructures and fibrils form in a Tris-buffered pH environment in a controlled manner through a temperature reduction and a pH shift. The lyophilized Zn2+: GnRH [6-D-Phe] assembly was tested as a platform for the sustained delivery of GnRH [6-D-Phe] and incorporated into two different oil vehicle matrices. The in vitro release was slow and continuous over 14 days and not influenced by the oil matrix

Uncovering relationships between view direction patterns and glare perception in a daylit workspace

This paper presents the results of an experimental study that aims to provide objective insights as to how luminance distribution in an office setting modulates our view direction (VD) in a daylit workspace while performing office tasks. Using the office-like test facility at Fraunhofer ISE (Freiburg, Germany) to create a range of controlled daylighting conditions, and a wearable mobile eye-tracker to measure eye and head orientation, we assessed VD distributions for subjects performing a standardized sequence of typical office tasks relative to two different daylight conditions: low contrast condition with no direct sunlight as compared to high contrast condition with direct sunlight coming into the room. Our results show that while the participants look more outside the window during a non-cognitive and non-visual office task, this effect is lower under the high contrast lighting conditions. Moreover, the focus of the VDs is on the task area when the participants are performing a task involving visual and cognitive activities

Investigation of gaze patterns in daylit workplaces: using eye-tracking methods to objectify view direction as a function of lighting conditions

Despite numerous efforts in developing glare indices through human assessment studies, predicting visual comfort in indoor environments still poses important challenges in design. A major limitation in discomfort glare indices is that they all ignore its dependencies on view direction. In this study we adopted eye-tracking methods in a series of human assessment experiments in order to record actual visual response when experiencing discomfort glare. We set up an experiment where the view directions distributions were monitored as the participants were working in a side-lit office with three different task-supports - monitor, paper and phone - on a standardized office task sequence. The participants were allocated randomly to two groups where they were exposed to two different views from the window. The results show that the “view outside the window” is the main determinant of view direction bias whenever the participant is not focused on any cognitive or visual office task procedure

Combining wearable eye-tracking with 4π light-field measurements: towards controlling all bottom-up and top-down factors driving overt attention during real-world tasks

For improvement of office space design, we intend to capture the full (4π) light-field of an office space, while measuring gaze, head direction, body position, blink rate, and pupil size along with task performance and subjective well-being during a variety of office tasks. Besides the immediate application aspects this will allow for the first time to have full control over task and visual input in a fully unconstrained real-world setting. In the study reported here, 52 participants performed office tasks that varied in the tools used (phone, computer, paper ) as well as in their mental load – input, output, reflection and interaction – and were recorded under various experimentally controlled lighting conditions and outside views. We analyze gaze allocation during these tasks, with a particular emphasis on the distinct roles of eye and head, as well as on the effects of discomfort glare

Systematic permutation testing in GWAS pathway analyses: identification of genetic networks in dilated cardiomyopathy and ulcerative colitis

Background: Genome wide association studies (GWAS) are applied to identify genetic loci, which are associated with complex traits and human diseases. Analogous to the evolution of gene expression analyses, pathway analyses have emerged as important tools to uncover functional networks of genome-wide association data. Usually, pathway analyses combine statistical methods with a priori available biological knowledge. To determine significance thresholds for associated pathways, correction for multiple testing and over-representation permutation testing is applied. Results: We systematically investigated the impact of three different permutation test approaches for over-representation analysis to detect false positive pathway candidates and evaluate them on genome-wide association data of Dilated Cardiomyopathy (DCM) and Ulcerative Colitis (UC). Our results provide evidence that the gold standard - permuting the case–control status – effectively improves specificity of GWAS pathway analysis. Although permutation of SNPs does not maintain linkage disequilibrium (LD), these permutations represent an alternative for GWAS data when case–control permutations are not possible. Gene permutations, however, did not add significantly to the specificity. Finally, we provide estimates on the required number of permutations for the investigated approaches. Conclusions: To discover potential false positive functional pathway candidates and to support the results from standard statistical tests such as the Hypergeometric test, permutation tests of case control data should be carried out. The most reasonable alternative was case–control permutation, if this is not possible, SNP permutations may be carried out. Our study also demonstrates that significance values converge rapidly with an increasing number of permutations. By applying the described statistical framework we were able to discover axon guidance, focal adhesion and calcium signaling as important DCM-related pathways and Intestinal immune network for IgA production as most significant UC pathway

Indirect protein quantification of drug-transforming enzymes using peptide group-specific immunoaffinity enrichment and mass spectrometry

Immunoaffinity enrichment of proteotypic peptides, coupled with selected reaction monitoring, enables indirect protein quantification. However the lack of suitable antibodies limits its widespread application. We developed a method in which multi-specific antibodies are used to enrich groups of peptides, thus facilitating multiplexed quantitative protein assays. We tested this strategy in a pharmacokinetic experiment by targeting a group of homologous drug transforming proteins in human hepatocytes. Our results indicate the generic applicability of this method to any biological system