The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: outcomes of a drug and disease model

Differences in treatment responses to ranibizumab injections observed within trials involving monthly (MARINA and ANCHOR studies) and quarterly (PIER study) treatment suggest that an individualized treatment regimen may be effective in neovascular age-related macular degeneration. In the present study, a drug and disease model was used to evaluate the impact of an individualized, flexible treatment regimen on disease progression.

Ragu: a free tool for the analysis of EEG and MEG event-related scalp field data using global randomization statistics

We present a program (Ragu; Randomization Graphical User interface) for statistical analyses of multichannel event-related EEG and MEG experiments. Based on measures of scalp field differences including all sensors, and using powerful, assumption-free randomization statistics, the program yields robust, physiologically meaningful conclusions based on the entire, untransformed, and unbiased set of measurements. Ragu accommodates up to two within-subject factors and one between-subject factor with multiple levels each. Significance is computed as function of time and can be controlled for type II errors with overall analyses. Results are displayed in an intuitive visual interface that allows further exploration of the findings. A sample analysis of an ERP experiment illustrates the different possibilities offered by Ragu. The aim of Ragu is to maximize statistical power while minimizing the need for a-priori choices of models and parameters (like inverse models or sensors of interest) that interact with and bias statistics.

Traffic-Adaptive and Link-Quality-Aware Communication in Wireless Sensor Networks

This paper is a summary of the main contribu- tions of the PhD thesis published in [1]. The main research contributions of the thesis are driven by the research question how to design simple, yet efficient and robust run-time adaptive resource allocation schemes within the commu- nication stack of Wireless Sensor Network (WSN) nodes. The thesis addresses several problem domains with con- tributions on different layers of the WSN communication stack. The main contributions can be summarized as follows: First, a a novel run-time adaptive MAC protocol is intro- duced, which stepwise allocates the power-hungry radio interface in an on-demand manner when the encountered traffic load requires it. Second, the thesis outlines a metho- dology for robust, reliable and accurate software-based energy-estimation, which is calculated at network run- time on the sensor node itself. Third, the thesis evaluates several Forward Error Correction (FEC) strategies to adap- tively allocate the correctional power of Error Correcting Codes (ECCs) to cope with timely and spatially variable bit error rates. Fourth, in the context of TCP-based communi- cations in WSNs, the thesis evaluates distributed caching and local retransmission strategies to overcome the perfor- mance degrading effects of packet corruption and trans- mission failures when transmitting data over multiple hops. The performance of all developed protocols are eval- uated on a self-developed real-world WSN testbed and achieve superior performance over selected existing ap- proaches, especially where traffic load and channel condi- tions are suspect to rapid variations over time.

Three-year results of visual outcome with disease activity-guided ranibizumab algorithm for the treatment of exudative age-related macular degeneration

PURPOSE To evaluate 3-year follow-up treatment outcomes with ranibizumab (Lucentis(®)) 0.5 mg administered either monthly or quarterly on a pro re nata (PRN) basis according to a disease activity-guided monitoring and treatment algorithm. METHODS A total of 316 treatment-naive eyes of 316 patients with exudative age-related macular degeneration met the criteria for inclusion in this retrospective, interventional case series. Patients were treated with ranibizumab 0.5 mg according to a disease activity-guided algorithm with monthly monitoring. Optical coherence tomography and fluorescein angiography were routinely used to assess disease activity: active lesions were treated with a series of three monthly injections, whereas inactive lesions were treated with quarterly injections. RESULTS Mean Early Treatment Diabetic Retinopathy Study best-corrected visual acuity improved from 52 letters at baseline to 59 letters at 12 months, achieved with a mean of 7.1 injections, 61 letters at 24 months with a mean of 5.0 injections administered in the second year and 60 letters at 36 months with a mean number of 5.2 injections. CONCLUSIONS Monthly visits and a morphology-driven PRN regimen with 3 injections in case of recurrence plus quarterly injections in case of inactive CNV resulted in an average VA gain of 7-9 letters that could be maintained over 3 years.

Visual symptoms in Parkinson's disease and Parkinson's disease dementia

Visual symptoms are common in PD and PD dementia and include difficulty reading, double vision, illusions, feelings of presence and passage, and complex visual hallucinations. Despite the established prognostic implications of complex visual hallucinations, the interaction between cognitive decline, visual impairment, and other visual symptoms remains poorly understood. Our aim was to characterize the spectrum of visual symptomatology in PD and examine clinical predictors for their occurrence. Sixty-four subjects with PD, 26 with PD dementia, and 32 age-matched controls were assessed for visual symptoms, cognitive impairment, and ocular pathology. Complex visual hallucinations were common in PD (17%) and PD dementia (89%). Dementia subjects reported illusions (65%) and presence (62%) more frequently than PD or control subjects, but the frequency of passage hallucinations in PD and PD dementia groups was equivalent (48% versus 69%, respectively; P = 0.102). Visual acuity and contrast sensitivity was impaired in parkinsonian subjects, with disease severity and age emerging as the key predictors. Regression analysis identified a variety of factors independently predictive of complex visual hallucinations (e.g., dementia, visual acuity, and depression), illusions (e.g., excessive daytime somnolence and disease severity), and presence (e.g., rapid eye movement sleep behavior disorder and excessive daytime somnolence). Our results demonstrate that different "hallucinatory" experiences in PD do not necessarily share common disease predictors and may, therefore, be driven by different pathophysiological mechanisms. If confirmed, such a finding will have important implications for future studies of visual symptoms and cognitive decline in PD and PD dementia.

Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis.

Communication in troubled waters: responses of fish communication systems to changing environments

Fish populations are increasingly being subjected to anthropogenic changes to their sensory environments. The impact of these changes on inter- and intra-specific communication, and its evolutionary consequences, has only recently started to receive research attention. A disruption of the sensory environment is likely to impact communication, especially with respect to reproductive interactions that help to maintain species boundaries. Aquatic ecosystems around the world are being threatened by a variety of environmental stressors, causing dramatic losses of biodiversity and bringing urgency to the need to understand how fish respond to rapid environmental changes. Here, we discuss current research on different communication systems (visual, chemical, acoustic, electric) and explore the state of our knowledge of how complex systems respond to environmental stressors using fish as a model. By far the bulk of our understanding comes from research on visual communication in the context of mate selection and competition for mates, while work on other communication systems is accumulating. In particular, it is increasingly acknowledged that environmental effects on one mode of communication may trigger compensation through other modalities. The strength and direction of selection on communication traits may vary if such compensation occurs. However, we find a dearth of studies that have taken a multimodal approach to investigating the evolutionary impact of environmental change on communication in fish. Future research should focus on the interaction between different modes of communication, especially under changing environmental conditions. Further, we see an urgent need for a better understanding of the evolutionary consequences of changes in communication systems on fish diversity.

Diffusion-driven transport in clayrock formations

Clay mineral-rich sedimentary formations are currently under investigation to evaluate their potential use as host formations for installation of deep underground disposal facilities for radioactive waste (e.g. Boom Clay (BE), Opalinus Clay (CH), Callovo-Oxfordian argillite (FR)). The ultimate safety of the corresponding repository concepts depends largely on the capacity of the host formation to limit the flux towards the biosphere of radionuclides (RN) contained in the waste to acceptably low levels. Data for diffusion-driven transfer in these formations shows extreme differences in the measured or modelled behaviour for various radionuclides, e. g. between halogen RN (Cl-36, I-129) and actinides (U-238,U-235, Np-237, Th-232, etc.), which result from major differences between RN of the effects on transport of two phenomena: diffusion and sorption. This paper describes recent research aimed at improving understanding of these two phenomena, focusing on the results of studies carried out during the EC Funmig IP on clayrocks from the above three formations and from the Boda formation (HU). Project results regarding phenomena governing water, cation and anion distribution and mobility in the pore volumes influenced by the negatively-charged surfaces of clay minerals show a convergence of the modelling results for behaviour at the molecular scale and descriptions based on electrical double layer models. Transport models exist which couple ion distribution relative to the clay-solution interface and differentiated diffusive characteristics. These codes are able to reproduce the main trends in behaviour observed experimentally, e.g. D-e(anion) < D-e(HTO) < D-e(cation) and D-e(anion) variations as a function of ionic strength and material density. These trends are also well-explained by models of transport through ideal porous matrices made up of a charged surface material. Experimental validation of these models is good as regards monovalent alkaline cations, in progress for divalent electrostatically-interacting cations (e.g. Sr2+) and still relatively poor for 'strongly sorbing', high K-d cations. Funmig results have clarified understanding of how clayrock mineral composition, and the corresponding organisation of mineral grain assemblages and their associated porosity, can affect mobile solute (anions, HTO) diffusion at different scales (mm to geological formation). In particular, advances made in the capacity to map clayrock mineral grain-porosity organisation at high resolution provide additional elements for understanding diffusion anisotropy and for relating diffusion characteristics measured at different scales. On the other hand, the results of studies focusing on evaluating the potential effects of heterogeneity on mobile species diffusion at the formation scale tend to show that there is a minimal effect when compared to a homogeneous property model. Finally, the results of a natural tracer-based study carried out on the Opalinus Clay formation increase confidence in the use of diffusion parameters measured on laboratory scale samples for predicting diffusion over geological time-space scales. Much effort was placed on improving understanding of coupled sorption-diffusion phenomena for sorbing cations in clayrocks. Results regarding sorption equilibrium in dispersed and compacted materials for weakly to moderately sorbing cations (Sr2+, Cs+, Co2+) tend to show that the same sorption model probably holds in both systems. It was not possible to demonstrate this for highly sorbing elements such as Eu(III) because of the extremely long times needed to reach equilibrium conditions, but there does not seem to be any clear reason why such elements should not have similar behaviour. Diffusion experiments carried out with Sr2+, Cs+ and Eu(III) on all of the clayrocks gave mixed results and tend to show that coupled diffusion-sorption migration is much more complex than expected, leading generally to greater mobility than that predicted by coupling a batch-determined K-d and Ficks law based on the diffusion behaviour of HTO. If the K-d measured on equivalent dispersed systems holds as was shown to be the case for Sr, Cs (and probably Co) for Opalinus Clay, these results indicate that these cations have a D-e value higher than HTO (up to a factor of 10 for Cs+). Results are as yet very limited for very moderate to strongly sorbing species (e.g. Co(II), Eu(III), Cu(II)) because of their very slow transfer characteristics. (C) 2011 Elsevier Ltd. All rights reserved.

Brain electric microstates and momentary conscious mind states as building blocks of spontaneous thinking: I. Visual imagery and abstract thoughts

Prompted reports of recall of spontaneous, conscious experiences were collected in a no-input, no-task, no-response paradigm (30 random prompts to each of 13 healthy volunteers). The mentation reports were classified into visual imagery and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was continuously recorded, viewed as series of momentary spatial distributions (maps) of the brain electric field and segmented into microstates, i.e. into time segments characterized by quasi-stable landscapes of potential distribution maps which showed varying durations in the sub-second range. Microstate segmentation used a data-driven strategy. Different microstates, i.e. different brain electric landscapes must have been generated by activity of different neural assemblies and therefore are hypothesized to constitute different functions. The two types of reported experiences were associated with significantly different microstates (mean duration 121 ms) immediately preceding the prompts; these microstates showed, across subjects, for abstract thought (compared to visual imagery) a shift of the electric gravity center to the left and a clockwise rotation of the field axis. Contrariwise, the microstates 2 s before the prompt did not differ between the two types of experiences. The results support the hypothesis that different microstates of the brain as recognized in its electric field implement different conscious, reportable mind states, i.e. different classes (types) of thoughts (mentations); thus, the microstates might be candidates for the `atoms of thought'.

Informative State-Based Video Communication

We study state-based video communication where a client simultaneously informs the server about the presence status of various packets in its buffer. In sender-driven transmission, the client periodically sends to the server a single acknowledgement packet that provides information about all packets that have arrived at the client by the time the acknowledgment is sent. In receiver-driven streaming, the client periodically sends to the server a single request packet that comprises a transmission schedule for sending missing data to the client over a horizon of time. We develop a comprehensive optimization framework that enables computing packet transmission decisions that maximize the end-to-end video quality for the given bandwidth resources, in both prospective scenarios. The core step of the optimization comprises computing the probability that a single packet will be communicated in error as a function of the expected transmission redundancy (or cost) used to communicate the packet. Through comprehensive simulation experiments, we carefully examine the performance advances that our framework enables relative to state-of-the-art scheduling systems that employ regular acknowledgement or request packets. Consistent gains in video quality of up to 2B are demonstrated across a variety of content types. We show that there is a direct analogy between the error-cost efficiency of streaming a single packet and the overall rate-distortion performance of streaming the whole content. In the case of sender-driven transmission, we develop an effective modeling approach that accurately characterizes the end-to-end performance as a function of the packet loss rate on the backward channel and the source encoding characteristics.

A versatile gas interface for routine radiocarbon analysis with a gas ion source

In 2010 more than 600 radiocarbon samples were measured with the gas ion source at the MIni CArbon DAting System (MICADAS) at ETH Zurich and the number of measurements is rising quickly. While most samples contain less than 50 mu g C at present, the gas ion source is attractive as well for larger samples because the time-consuming graphitization is omitted. Additionally, modern samples are now measured down to 5 per-mill counting statistics in less than 30 min with the recently improved gas ion source. In the versatile gas handling system, a stepping-motor-driven syringe presses a mixture of helium and sample CO2 into the gas ion source, allowing continuous and stable measurements of different kinds of samples. CO2 can be provided in four different ways to the versatile gas interface. As a primary method. CO2 is delivered in glass or quartz ampoules. In this case, the CO2 is released in an automated ampoule cracker with 8 positions for individual samples. Secondly, OX-1 and blank gas in helium can be provided to the syringe by directly connecting gas bottles to the gas interface at the stage of the cracker. Thirdly, solid samples can be combusted in an elemental analyzer or in a thermo-optical OC/EC aerosol analyzer where the produced CO2 is transferred to the syringe via a zeolite trap for gas concentration. As a fourth method, CO2 is released from carbonates with phosphoric acid in septum-sealed vials and loaded onto the same trap used for the elemental analyzer. All four methods allow complete automation of the measurement, even though minor user input is presently still required. Details on the setup, versatility and applications of the gas handling system are given. (C) 2012 Elsevier B.V. All rights reserved.

Vitreoretinal Interface Changes in Geographic Atrophy.

PURPOSE Geographic atrophy (GA) is the end-stage manifestation of atrophic age-related macular degeneration (AMD). The disease progresses slowly over time, eventually causing loss of central vision. Its cause and pathomechanism are not fully known. Previous studies have suggested that vitreoretinal traction (VRT) may contribute to the progression of neovascular AMD. The aim of this study was to examine whether an association between changes at the vitreoretinal interface (VRI), in particular traction (VRT), and the characteristics and progression of GA in eyes with dry AMD can be established. DESIGN Clinic-based prospective cohort study. PARTICIPANTS A total of 97 patients (age range, 61-90 years; mean, 78.4 years) with GA secondary to dry AMD were enrolled. Patients exhibiting neovascular signs on fluorescein angiography in either eye were excluded. METHODS The VRI changes were examined using spectral-domain optical coherence tomography (SD-OCT). Characteristics of GA were examined using fundus autofluorescence (FAF) imaging. All imaging was performed using a Spectralis SLO+OCT device (Heidelberg Engineering, Heidelberg, Germany); GA area was measured using the Region Finder (Heidelberg Engineering) software native to the Spectralis platform. MAIN OUTCOME MEASURES Area and increase in area of GA. RESULTS A total of 97 eyes were examined. Vitreoretinal traction was found in 39 eyes (40%). The GA area at baseline was 6.65±5.64 mm(2) in eyes with VRT and 5.73±4.72 mm(2) in eyes with no VRT. The annual rate of progression of GA area progression was 2.99±0.66 mm(2) in eyes with VRT and 1.45±0.67mm(2) in eyes without VRT. Differences between groups in both parameters were statistically significant (n = 97 total number of eyes; P<0.001). Multiple regression analysis confirmed this finding (B = 0.714, P<0.001; F3,93 = 72.542, P<0.001; adjusted R(2) = 0.691) CONCLUSIONS: Our results indicate an association between VRT and an increased rate of progression of GA area in dry AMD. Monitoring VRT may contribute to an improved estimate of the prospective time of visual loss and to a better timing of emerging therapies in dry AMD.