111 research outputs found

    The Bilingual Muse

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    The Bilingual Muse analyzes the work of seven Russian poets who translated their own poems into English, French, German, or Italian. Investigating the parallel versions of self-translated poetic texts by Vladimir Nabokov, Joseph Brodsky, Andrey Gritsman, Katia Kapovich, Marina Tsvetaeva, Wassily Kandinsky, and Elizaveta Kul’man, Adrian Wanner considers how verbal creativity functions in different languages, the conundrum of translation, and the vagaries of bilingual identities. Wanner argues that the perceived marginality of self-translation stems from a romantic privileging of the mother tongue and the original text. The unprecedented recent dispersion of Russian speakers over three continents has led to the emergence of a new generation of diasporic Russians who provide a more receptive milieu for multilingual creativity

    Reconstruction of neuronal activity and connectivity patterns in the zebrafish olfactory bulb

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    In the olfactory bulb (OB), odors evoke distributed patterns of activity across glomeruli that are reorganized by networks of interneurons (INs). This reorganization results in multiple computations including a decorrelation of activity patterns across the output neurons, the mitral cells (MCs). To understand the mechanistic basis of these computations it is essential to analyze the relationship between function and structure of the underlying circuit. I combined in vivo twophoton calcium imaging with dense circuit reconstruction from complete serial block-face electron microscopy (SBEM) stacks of the larval zebrafish OB (4.5 dpf) with a voxel size of 9x9x25nm. To address bottlenecks in the workflow of SBEM, I developed a novel embedding and staining procedure that effectively reduces surface charging in SBEM and enables to acquire SBEM stacks with at least a ten-fold increase in both, signal-to-noise as well as acquisition speed. I set up a high throughput neuron reconstruction pipeline with >30 professional tracers that is available for the scientific community (ariadne-service.com). To assure efficient and accurate circuit reconstruction, I developed PyKNOSSOS, a Python software for skeleton tracing and synapse annotation, and CORE, a skeleton consolidation procedure that combines redundant reconstruction with targeted expert input. Using these procedures I reconstructed all neurons (>1000) in the larval OB. Unlike in the adult OB, INs were rare and appeared to represent specific subtypes, indicating that different sub-circuits develop sequentially. MCs were uniglomerular whereas inter-glomerular projections of INs were complex and biased towards groups of glomeruli that receive input from common types of sensory neurons. Hence, the IN network in the OB exhibits a topological organization that is governed by glomerular identity. Calcium imaging revealed that the larval OB circuitry already decorrelates activity patterns evoked by similar odors. The comparison of inter-glomerular connectivity to the functional interactions between glomeruli indicates that pattern decorrelation depends on specific, non-random inter-glomerular IN projections. Hence, the topology of IN networks in the OB appears to be an important determinant of circuit function

    Methods for Mapping Neuronal Activity to Synaptic Connectivity: Lessons From Larval Zebrafish

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    For a mechanistic understanding of neuronal circuits in the brain, a detailed description of information flow is necessary. Thereby it is crucial to link neuron function to the underlying circuit structure. Multiphoton calcium imaging is the standard technique to record the activity of hundreds of neurons simultaneously. Similarly, recent advances in high-throughput electron microscopy techniques allow for the reconstruction of synaptic resolution wiring diagrams. These two methods can be combined to study both function and structure in the same specimen. Due to its small size and optical transparency, the larval zebrafish brain is one of the very few vertebrate systems where both, activity and connectivity of all neurons from entire, anatomically defined brain regions, can be analyzed. Here, we describe different methods and the tools required for combining multiphoton microscopy with dense circuit reconstruction from electron microscopy stacks of entire brain regions in the larval zebrafish

    Process Selection in RPA Projects – Towards a Quantifiable Method of Decision Making

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    The digital age requires companies to invest in value-creating rather than routine activities to drive innovation as a future source of competitiveness and business success. Thus, many companies are reluctant to invest in large-scale, costly backend integration projects and seek adaptable solutions to automate their front-office activities. Bridging artificial intelligence and business process management, robotic process automation (RPA) provides the promise of robots as a virtual workforce that performs these tasks in a self-determined manner. Many studies have highlighted potential benefits of RPA. However, little data is available on operationalizing and automating RPA to maximize its benefits. In this paper, we shed light on the automation potential of processes with RPA and operationalize it. Based on process mining techniques, we propose an automatable indicator system as well as present and evaluate decision support for companies that seek to better prioritize their RPA activities and to maximize their return on investment

    Patient-Specific Three-Dimensional Composite Bone Models for Teaching and Operation Planning

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    Background: Orthopedic trauma care relies on two-dimensional radiograms both before and during the operation. Understanding the three-dimensional nature of complex fractures on plain radiograms is challenging. Modern fluoroscopes can acquire three-dimensional volume datasets even during an operation, but the device limitations constrain the acquired volume to a cube of only 12-cm edge. However, viewing the surrounding intact structures is important to comprehend the fracture in its context. We suggest merging a fluoroscope's volume scan into a generic bone model to form a composite full-length 3D bone model. Methods: Materials consisted of one cadaver bone and 20 three-dimensional surface models of human femora. Radiograms and computed tomography scans were taken before and after applying a controlled fracture to the bone. A 3D scan of the fracture was acquired using a mobile fluoroscope (Siemens Siremobil). The fracture was fitted into the generic bone models by rigid registration using a modified least-squares algorithm. Registration precision was determined and a clinical appraisal of the composite models obtained. Results: Twenty composite bone models were generated. Average registration precision was 2.0mm (range 1.6 to 2.6). Average processing time on a laptop computer was 35s (range 20 to 55). Comparing synthesized radiograms with the actual radiograms of the fractured bone yielded clinically satisfactory results. Conclusion: A three-dimensional full-length representation of a fractured bone can reliably be synthesized from a short scan of the patient's fracture and a generic bone model. This patient-specific model can subsequently be used for teaching, surgical operation planning, and intraoperative visualization purpose

    The future of European Nephrology 'Guidelines' - a declaration of intent by European Renal Best Practice (ERBP)

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    The disparities of medical practice, together with a growing number of possible interventions, have increased the demand for well-conceived guidance for practitioners [1]. However, this development is hampered by the number and quality of scientific studies that test medical hypotheses, which are often unsatisfactory. This is especially true in nephrology, where well-conducted controlled trials are rare [2]. Because patients with renal failure are generally excluded from controlled studies in the general population [3], the development of sufficiently well-founded guidance in nephrology has always been difficult. With the development of European Best Practice Guidelines (EBPG), the European Renal Association–European Dialysis and Transplantation Association (ERA–EDTA) has created its own guidance-generating process. Similar initiatives have also arisen in the USA (Kidney Disease Outcome Initiative—K/DOQI), Australia (Caring for Australasians with Renal Impairment—CARI), Canada (Canadian Society of Nephrology—CSN), the UK (United Kingdom Renal Association—UKRA), as well as at several other locations around the world. These institutions have generated a plethora of often parallel recommendations on similar topics but sometimes with different messages [4]. The question can be asked: ‘Is there still a place for an institution generating European nephrology guidance?’ If there is, how should such an initiative be managed to conform with current demands? To answer these questions, the Council of ERA–EDTA set up a commission that convened three times in the course of 2008–09. The present text is a distillation of the discussions, reflections and final conclusions of this commission. It is an ad hoc document, reflecting the current status. In the future, concepts and attitudes might change, as medical thinking is influenced by changes in practice, needs, general philosophy, ethics and political/financial conditions

    Associations between domains of physical activity, sitting time, and different measures of overweight and obesity

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    AbstractObjectiveTo describe 1) cross-sectional associations between domain-specific physical activity, sitting time and different measures of overweight/obesity and 2) longitudinal associations between patterns of change in physical activity and overweight/obesity ten years later.MethodsCross-sectional and longitudinal analyses based on the first and second follow-up of the Swiss cohort study SAPALDIA (SAP) were conducted (SAP2 in 2002/03, SAP3 in 2010/11). Physical activity was assessed by self-report using the long International Physical Activity Questionnaire (IPAQ) and four short questions regarding moderate and vigorous activities. Overweight/obesity were defined based on body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and percent body fat based on bioelectric impedance analysis (BIA), all measured objectively. Multivariable logistic regression was used for analyses.ResultsCross-sectionally, leisure-time and vigorous physical activity were inversely associated with all obesity parameters. Most consistent associations were found with BIA percent body fat. There were no associations between work-related and domestic activities and overweight/obesity. Sitting time was positively associated with BIA percent body fat, but not with BMI, WHR and WHtR. Longitudinally, remaining inactive from SAP2 to SAP3 was associated with obesity and BIA percent body fat at SAP3 and with weight increase, becoming inactive with BIA percent body fat and weight increase.ConclusionsThe results support associations between physical activity and overweight/obesity cross-sectionally and longitudinally. Most consistent associations were found for BIA percent body fat. For prevention purposes, the results indicate that physical activity can have an important contribution to weight management

    Post hoc analysis of the SONAR trial indicates that the endothelin receptor antagonist atrasentan is associated with less pain in patients with type 2 diabetes and chronic kidney disease

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    Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). The management of chronic pain in these patients is limited by nephrotoxicity of commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since previous studies implicated endothelin-1 in pain nociception, our post hoc analysis of the SONAR trial assessed the association between the endothelin receptor antagonist atrasentan and pain and prescription of analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical trial that recruited participants with type 2 diabetes and CKD (estimated glomerular filtration rate 25–75 ml/min/1.73 m2; urinary albumin-to-creatinine ratio 300–5000 mg/g). Participants were randomized to receive atrasentan or placebo (1834 each arm). The main outcome was pain-related adverse events (AEs) reported by investigators. We applied Cox regression to assess the effect of atrasentan compared to placebo on the risk of the first reported pain-related AE and, secondly, first prescription of analgesics. We used the Anderson-Gill method to assess effects on all (first and subsequent) pain-related AEs. During 2.2-year median follow-up, 1183 pain-related AEs occurred. Rates for the first pain-related event were 138.2 and 170.2 per 1000 person-years in the atrasentan and placebo group respectively (hazard ratio 0.82 [95% confidence interval 0.72–0.93]). Atrasentan also reduced the rate of all (first and subsequent) pain-related AEs (rate ratio 0.80 [0.70-0.91]). These findings were similar after accounting for competing risk of death (sub-hazard ratio 0.81 [0.71–0.92]). Patients treated with atrasentan initiated fewer analgesics including NSAIDs and opioids compared to placebo during follow-up (hazard ratio = 0.72 [0.60–0.88]). Thus, atrasentan was associated with reduced pain-related events and pain-related use of analgesics in carefully selected patients with type 2 diabetes and CKD
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