Time-Resolved Ultra–High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina Therapy

Purpose: Selective retina therapy (SRT) is a novel treatment for retinal pathologies, solely targeting the retinal pigment epithelium (RPE). During SRT, the detection of an immediate tissue reaction is challenging as tissue effects remain limited to intracellular RPE photodisruption. Time-resolved ultra-high axial resolution optical coherence tomography (OCT) is thus evaluated for the monitoring of dynamic optical changes at and around the RPE during SRT. Methods: An experimental OCT system with an ultra-high axial resolution of 1.78 µm was combined with an SRT system and time-resolved OCT M-scans of the target area were recorded from four patients undergoing SRT. OCT scans were analyzed and OCT morphology was correlated with findings in fluorescein angiography, fundus photography and cross-sectional OCT. Results: In cases where the irradiation caused RPE damage proven by fluorescein angiography, the lesions were well discernible in time-resolved OCT images but remained invisible in fundus photography and cross-sectional OCT acquired after treatment. If RPE damage was introduced, all applied SRT pulses led to detectable signal changes in the time-resolved OCT images. The extent of optical signal variation seen in the OCT data appeared to scale with the applied SRT pulse energy. Conclusion: The first clinical results proved that successful SRT irradiation induces detectable changes in the OCT M-scan signal while it remains invisible in conventional ophthalmoscopic imaging. Thus, real-time high-resolution OCT is a promising modality to monitor and analyze tissue effects introduced by selective retina therapy and may be used to guide SRT in an automatic feedback mode.

Photometric monitoring of non-resolved space debris and databases of optical light curves.

The population of space debris increased drastically during the last years. Collisions involving massive objects may produce large number of fragments leading to significantly growth of the space debris population. An effective remediation measure in order to stabilize the population in LEO, is therefore the removal of large, massive space debris. To remove these objects, not only precise orbits, but also more detailed information about their attitude states will be required. One important property of an object targeted for removal is its spin period and spin axis orientation. If we observe a rotating object, the observer sees different surface areas of the object which leads to changes in the measured intensity. Rotating objects will produce periodic brightness vari ations with frequencies which are related to the spin periods. Photometric monitoring is the real tool for remote diagnostics of the satellite rotation around its center of mass. This information is also useful, for example, in case of contingency. Moreover, it is also important to take into account the orientation of non-spherical body (e.g. space debris) in the numerical integration of its motion when a close approach with the another spacecr aft is predicted. We introduce the two databases of light curves: the AIUB data base, which contains about a thousand light curves of LEO, MEO and high-altitude debris objects (including a few functional objects) obtained over more than seven years, and the data base of the Astronomical Observatory of Odessa University (Ukraine), which contains the results of more than 10 years of photometric monitoring of functioning satellites and large space debris objects in low Earth orbit. AIUB used its 1m ZIMLAT telescope for all light curves. For tracking low-orbit satellites, the Astronomical Observatory of Odessa used the KT-50 telescope, which has an alt-azimuth mount and allows tracking objects moving at a high angular velocity. The diameter of the KT-50 main mirror is 0.5 m, and the focal length is 3 m. The Odessa's Atlas of light curves includes almost 5,5 thousand light curves for ~500 correlated objects from a time period of 2005-2014. The processing of light curves and the determination of the rotation period in the inertial frame is challenging. Extracted frequencies and reconstructed phases for some interesting targets, e.g. GLONASS satellites, for which also SLR data were available for confirmation, will be presented. The rotation of the Envisat satellite after its sudden failure will be analyzed. The deceleration of its rotation rate within 3 years is studied together with the attempt to determine the orientation of the rotation axis.

An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

Reduced foveal vision enhances peripheral monitoring and peripheral event detection

Introduction: Although it seems plausible that sports performance relies on high-acuity foveal vision, it could be empirically shown that myoptic blur (up to +2 diopters) does not harm performance in sport tasks that require foveal information pick-up like golf putting (Bulson, Ciuffreda, & Hung, 2008). How myoptic blur affects peripheral performance is yet unknown. Attention might be less needed for processing visual cues foveally and lead to better performance because peripheral cues are better processed as a function of reduced foveal vision, which will be tested in the current experiment. Methods: 18 sport science students with self-reported myopia volunteered as participants, all of them regularly wearing contact lenses. Exclusion criteria comprised visual correction other than myopic, correction of astigmatism and use of contact lenses out of Swiss delivery area. For each of the participants, three pairs of additional contact lenses (besides their regular lenses; used in the “plano” condition) were manufactured with an individual overcorrection to a retinal defocus of +1 to +3 diopters (referred to as “+1.00 D”, “+2.00 D”, and “+3.00 D” condition, respectively). Gaze data were acquired while participants had to perform a multiple object tracking (MOT) task that required to track 4 out of 10 moving stimuli. In addition, in 66.7 % of all trials, one of the 4 targets suddenly stopped during the motion phase for a period of 0.5 s. Stimuli moved in front of a picture of a sports hall to allow for foveal processing. Due to the directional hypotheses, the level of significance for one-tailed tests on differences was set at α = .05 and posteriori effect sizes were computed as partial eta squares (ηρ2). Results: Due to problems with the gaze-data collection, 3 participants had to be excluded from further analyses. The expectation of a centroid strategy was confirmed because gaze was closer to the centroid than the target (all p < .01). In comparison to the plano baseline, participants more often recalled all 4 targets under defocus conditions, F(1,14) = 26.13, p < .01, ηρ2 = .65. The three defocus conditions differed significantly, F(2,28) = 2.56, p = .05, ηρ2 = .16, with a higher accuracy as a function of a defocus increase and significant contrasts between conditions +1.00 D and +2.00 D (p = .03) and +1.00 D and +3.00 D (p = .03). For stop trials, significant differences could neither be found between plano baseline and defocus conditions, F(1,14) = .19, p = .67, ηρ2 = .01, nor between the three defocus conditions, F(2,28) = 1.09, p = .18, ηρ2 = .07. Participants reacted faster in “4 correct+button” trials under defocus than under plano-baseline conditions, F(1,14) = 10.77, p < .01, ηρ2 = .44. The defocus conditions differed significantly, F(2,28) = 6.16, p < .01, ηρ2 = .31, with shorter response times as a function of a defocus increase and significant contrasts between +1.00 D and +2.00 D (p = .01) and +1.00 D and +3.00 D (p < .01). Discussion: The results show that gaze behaviour in MOT is not affected to a relevant degree by a visual overcorrection up to +3 diopters. Hence, it can be taken for granted that peripheral event detection was investigated in the present study. This overcorrection, however, does not harm the capability to peripherally track objects. Moreover, if an event has to be detected peripherally, neither response accuracy nor response time is negatively affected. Findings could claim considerable relevance for all sport situations in which peripheral vision is required which now needs applied studies on this topic. References: Bulson, R. C., Ciuffreda, K. J., & Hung, G. K. (2008). The effect of retinal defocus on golf putting. Ophthalmic and Physiological Optics, 28, 334-344.

Future water quality monitoring--adapting tools to deal with mixtures of pollutants in water resource management.

Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects of anthropogenic chemical contamination from diffuse and point sources. While current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals can be detected simultaneously in our aquatic resources. However, exposure to chemical mixtures does not necessarily translate into adverse biological effects nor clearly shows whether mitigation measures are needed. Thus, the question which mixtures are present and which have associated combined effects becomes central for defining adequate monitoring and assessment strategies. Here we describe the vision of the international, EU-funded project SOLUTIONS, where three routes are explored to link the occurrence of chemical mixtures at specific sites to the assessment of adverse biological combination effects. First of all, multi-residue target and non-target screening techniques covering a broader range of anticipated chemicals co-occurring in the environment are being developed. By improving sensitivity and detection limits for known bioactive compounds of concern, new analytical chemistry data for multiple components can be obtained and used to characterise priority mixtures. This information on chemical occurrence will be used to predict mixture toxicity and to derive combined effect estimates suitable for advancing environmental quality standards. Secondly, bioanalytical tools will be explored to provide aggregate bioactivity measures integrating all components that produce common (adverse) outcomes even for mixtures of varying compositions. The ambition is to provide comprehensive arrays of effect-based tools and trait-based field observations that link multiple chemical exposures to various environmental protection goals more directly and to provide improved in situ observations for impact assessment of mixtures. Thirdly, effect-directed analysis (EDA) will be applied to identify major drivers of mixture toxicity. Refinements of EDA include the use of statistical approaches with monitoring information for guidance of experimental EDA studies. These three approaches will be explored using case studies at the Danube and Rhine river basins as well as rivers of the Iberian Peninsula. The synthesis of findings will be organised to provide guidance for future solution-oriented environmental monitoring and explore more systematic ways to assess mixture exposures and combination effects in future water quality monitoring.

Investigating the potential of reported cattle mortality data in Switzerland for syndromic surveillance

Systems for the identification and registration of cattle have gradually been receiving attention for use in syndromic surveillance, a relatively recent approach for the early detection of infectious disease outbreaks. Real or near real-time monitoring of deaths or stillbirths reported to these systems offer an opportunity to detect temporal or spatial clusters of increased mortality that could be caused by an infectious disease epidemic. In Switzerland, such data are recorded in the "Tierverkehrsdatenbank" (TVD). To investigate the potential of the Swiss TVD for syndromic surveillance, 3 years of data (2009-2011) were assessed in terms of data quality, including timeliness of reporting and completeness of geographic data. Two time-series consisting of reported on-farm deaths and stillbirths were retrospectively analysed to define and quantify the temporal patterns that result from non-health related factors. Geographic data were almost always present in the TVD data; often at different spatial scales. On-farm deaths were reported to the database by farmers in a timely fashion; stillbirths were less timely. Timeliness and geographic coverage are two important features of disease surveillance systems, highlighting the suitability of the TVD for use in a syndromic surveillance system. Both time series exhibited different temporal patterns that were associated with non-health related factors. To avoid false positive signals, these patterns need to be removed from the data or accounted for in some way before applying aberration detection algorithms in real-time. Evaluating mortality data reported to systems for the identification and registration of cattle is of value for comparing national data systems and as a first step towards a European-wide early detection system for emerging and re-emerging cattle diseases.

[Health Status of Young Men in Switzerland: Monitoring Results from Conscription].

Abstract Due to their representativeness and consistent measurement standards the medical und sports data of the Swiss conscripts provide a valuable basis for a continuous health monitoring of young Swiss men. During three to four years, the prevalence of overweight and obesity seems to stabilise on a high level. After a longer period of decreasing performance at the endurance test between the 1980s and 2002, the level of physical performance in the fitness test does no longer decrease since 2006. However, health and health behaviour show significant regional and socioeconomic inequalities among young Swiss men. Besides economic resources and education, major driving factors behind these inequalities can be identified in health knowledge, values, and attitudes.