Photoreceptor vitality in organotypic cultures of mature vertebrate retinas validated by light-dependent molecular movements

AbstractVertebrate photoreceptor cells are polarized neurons highly specialized for light absorption and visual signal transduction. Photoreceptor cells consist of the light sensitive outer segment and the biosynthetic active inner segment linked by a slender connecting cilium. The function of mature photoreceptor cells is strictly dependent on this compartmentalization which is maintained in the specialized retinal environment. To keep this fragile morphologic and functional composition for further cell biological studies and treatments we established organotypic retina cultures of mature mice and Xenopus laevis. The organotypic retina cultures of both model organisms are created as co-cultures of the retina and the pigment epithelium, still attached to outer segments of the photoreceptor cells. To demonstrate the suitability of the culture system for physiological analyses we performed apoptotic cell death analyses and verified photoreceptor viability. Furthermore, light-dependent bidirectional movements of arrestin and transducin in photoreceptors in vivo and in the retinal cultures were indistinguishable indicating normal photoreceptor cell-biologic function in organotypic cultures. Our established culture systems allow the analysis of mature photoreceptor cells and their accessibility to treatments, characteristic for common cell culture. Furthermore, this culturing technique also provides an appropriate system for gene delivery to retinal cells and will serve to simulate gene therapeutic approaches prior to difficult and time-consuming in vivo experiments

An evaluation of data quality in Canada’s Continuing Care Reporting System (CCRS): secondary analyses of Ontario data submitted between 1996 and 2011

Abstract Background Evidence informed decision making in health policy development and clinical practice depends on the availability of valid and reliable data. The introduction of interRAI assessment systems in many countries has provided valuable new information that can be used to support case mix based payment systems, quality monitoring, outcome measurement and care planning. The Continuing Care Reporting System (CCRS) managed by the Canadian Institute for Health Information has served as a data repository supporting national implementation of the Resident Assessment Instrument (RAI 2.0) in Canada for more than 15 years. The present paper aims to evaluate data quality for the CCRS using an approach that may be generalizable to comparable data holdings internationally. Methods Data from the RAI 2.0 implementation in Complex Continuing Care (CCC) hospitals/units and Long Term Care (LTC) homes in Ontario were analyzed using various statistical techniques that provide evidence for trends in validity, reliability, and population attributes. Time series comparisons included evaluations of scale reliability, patterns of associations between items and scales that provide evidence about convergent validity, and measures of changes in population characteristics over time. Results Data quality with respect to reliability, validity, completeness and freedom from logical coding errors was consistently high for the CCRS in both CCC and LTC settings. The addition of logic checks further improved data quality in both settings. The only notable change of concern was a substantial inflation in the percentage of long term care home residents qualifying for the Special Rehabilitation level of the Resource Utilization Groups (RUG-III) case mix system after the adoption of that system as part of the payment system for LTC. Conclusions The CCRS provides a robust, high quality data source that may be used to inform policy, clinical practice and service delivery in Ontario. Only one area of concern was noted, and the statistical techniques employed here may be readily used to target organizations with data quality problems in that (or any other) area. There was also evidence that data quality was good in both CCC and LTC settings from the outset of implementation, meaning data may be used from the entire time series. The methods employed here may continue to be used to monitor data quality in this province over time and they provide a benchmark for comparisons with other jurisdictions implementing the RAI 2.0 in similar populations.http://deepblue.lib.umich.edu/bitstream/2027.42/112338/1/12911_2012_Article_635.pd

Mechanistic Basis for the Failure of Cone Transducin to Translocate: Why Cones Are Never Blinded by Light

The remarkable ability of our vision to function under ever-changing conditions of ambient illumination is mediated by multiple molecular mechanisms regulating the light-sensitivity of rods and cones. One such mechanism involves massive translocation of signaling proteins, including the G protein transducin, into and out of the light-sensitive photoreceptor outer segment compartment. Transducin translocation extends the operating range of rods, but in cones transducin never translocates, which is puzzling because cones typically function in much brighter light than rods. Using genetically manipulated mice in which the rates of transducin activation and inactivation were altered, we demonstrate that, like in rods, transducin translocation in cones can be triggered when transducin activation exceeds a critical level essentially saturating the photoresponse. However, this level is never achieved in wild type cones: their superior ability to tightly control the rates of transducin activation and inactivation, responsible for avoiding saturation by light, also accounts for prevention of transducin translocation at any light intensity

Postsurgical pain outcome of vertical and transverse abdominal incision: Design of a randomized controlled equivalence trial [ISRCTN60734227]

BACKGROUND: There are two ways to open the abdominal cavity in elective general surgery: vertically or transversely. Various clinical studies and a meta-analysis have postulated that the transverse approach is superior to other approaches as regards complications. However, in a recent survey it was shown that 90 % of all abdominal incisions in visceral surgery are still vertical incisions. This discrepancy between existing recommendations of clinical trials and clinical practice could be explained by the lack of acceptance of these results due to a number of deficits in the study design and analysis, subsequent low internal validity, and therefore limited external generalisability. The objective of this study is to address the issue from the patient's perspective. METHODS: This is an intraoperatively randomized controlled observer and patient-blinded two-group parallel equivalence trial. The study setting is the Department of General-, Visceral-, Trauma Surgery and Outpatient Clinic of the University of Heidelberg, Medical School. A total of 172 patients of both genders, aged over 18 years who are scheduled for an elective abdominal operation and are eligible for either a transverse or vertical incision. To show equivalence of the two approaches or the superiority of one of them from the perspective of the patient, a primary endpoint is defined: the pain experienced by the patient (VAS 0–100) on day two after surgery and the amount of analgesic required (piritramide [mg/h]). A confidence interval approach will be used for analysis. A global α-Level of 0.05 and a power of 0.8 is guaranteed, resulting in a size of 86 patients for each group. Secondary endpoints are: time interval to open and close the abdomen, early-onset complications (frequency of burst abdomen, postoperative pulmonary complications, and wound infection) and late complications (frequency of incisional hernias). Different outcome variables will be ranked by patients and surgeons to assess the relevance of possible endpoints from the patients' and surgeons' perspective. CONCLUSION: This is a randomized controlled observer and patient-blinded two-group parallel trial to answer the question if the transverse abdominal incision is equivalent to the vertical one due to the described endpoints

Draft low level waste technical summary

The purpose of this document is to present an outline of the Hanford Site Low-Level Waste (LLW) disposal program, what it has accomplished, what is being done, and where the program is headed. This document may be used to provide background information to personnel new to the LLW management/disposal field and to those individuals needing more information or background on an area in LLW for which they are not familiar. This document should be appropriate for outside groups that may want to learn about the program without immediately becoming immersed in the details. This document is not a program or systems engineering baseline report, and personnel should refer to more current baseline documentation for critical information

On Distant Speech Recognition for Home Automation

The official version of this draft is available at Springer via http://dx.doi.org/10.1007/978-3-319-16226-3_7International audienceIn the framework of Ambient Assisted Living, home automation may be a solution for helping elderly people living alone at home. This study is part of the Sweet-Home project which aims at developing a new home automation system based on voice command to improve support and well-being of people in loss of autonomy. The goal of the study is vocal order recognition with a focus on two aspects: distance speech recognition and sentence spotting. Several ASR techniques were evaluated on a realistic corpus acquired in a 4-room flat equipped with microphones set in the ceiling. This distant speech French corpus was recorded with 21 speakers who acted scenarios of activities of daily living. Techniques acting at the decoding stage, such as our novel approach called Driven Decoding Algorithm (DDA), gave better speech recognition results than the baseline and other approaches. This solution which uses the two best SNR channels and a priori knowledge (voice commands and distress sentences) has demonstrated an increase in recognition rate without introducing false alarms

A concept for trial institutions focussing on randomised controlled trials in surgery

<p>Abstract</p> <p>Background</p> <p>Although considered the reference standard for generating valid scientific evidence of a treatment's benefits and harms, the number of Randomised Controlled Trials (RCT) comparing surgical techniques remains low. Much effort has been made in order to overcome methodological issues and improve quality of RCTs in surgery. To the present there has been, however, only little emphasis on development and maintenance of institutions for implementation of adequately designed and conducted surgical RCTs.</p> <p>Mehods/Design</p> <p>Description of the developments in surgical RCT infrastructure in Germany between 2001 and 2006. Cross sectional evaluation of completed and ongoing surgical RCTs within the German Surgical Society and the Clinical Study Centre, Department of Surgery, University of Heidelberg.</p> <p>Results</p> <p>Foundation of a national Clinical Trial Centre (CTC) for the organisation of multi-centre RCTs in the surgical setting (Study Center of the German Surgical Society, SDGC). Establishment of a network of CTCs with affiliated Clinical Sites (CSs) to enhance patient recruitment and shorten the duration of RCTs. Since its foundation four surgical RCTs with a total sample size of 1650 patients (1006 of these randomised) have been supervised by the SDGC with 35 CSs involved in patient recruitment. Five further CTCs were set up in 2006. Together with their affiliated CSs a network has been organised providing improved conditions for the conduction of surgical RCTs.</p> <p>Conclusion</p> <p>Improvement of infrastructure substantially facilitates integration of RCTs into routine surgical practice. A network of collaborating CTCs and CSs can provide an adequate infrastructure for the conduction of multi-centre RCTs.</p

Scaling of columnar joints in basalt

We describe field work, analysis, and modeling of columnar joints from the Columbia River Basalt Group. This work is focused on the regions around the Grand Coulee, Snake River, and Columbia Gorge, which form parts of this unusually homogeneous and very large sample of columnar basalt. We examine in detail the scaling relationship between the column width and the size of the striae and relate these quantitatively to thermal and fracture models. We found that the column radius and stria size are proportional to each other and inversely proportional to the cooling rate of the lava. Near a flow margin, our results put observational constraints on diffusive thermal models of joint formation. Deeper than a few meters into a colonnade, our measurements are consistent with a simple advection-diffusion model of two-phase convective cooling within the joints, regardless of the direction of cooling. This model allows an accurate comparison of igneous columnar jointing and joints due to desiccation in laboratory analog systems. We also identify a new length scale in which wavy columns can appear in some colonnades. The mechanisms leading to the wavy columns are likely related to those underlying similar wavy cracks in 2-D analog systems

Affective processes as network hubs

The practical problems of designing and coding a web-based flight simulator for teachers has led to a ‘three-tier plus environment’ model (COVE model) for a software agent’s cognition (C), psychologicsal (O), physical (V) processes and responses to tasks and interpersonal relationships within a learning environment (E). The purpose of this article is to introduce how some of the COVE model layers represent preconscious processing hubs in an AI human-agent’s representation of learning in a serious game, and how an application of the Five Factor Model of psychology in the O layer determines the scope of dimensions for a practical computational model of affective processes. The article illustrates the model with the classroom-learning context of the simSchool application (www.simschool.org); presents details of the COVE model of an agent’s reactions to academic tasks; discusses the theoretical foundations; and outlines the research-based real world impacts from external validation studies as well as new testable hypotheses of simSchool