Testing Navigation in Real Space: Contributions to Understanding the Physiology and Pathology of Human Navigation Control

Successful navigation relies on the flexible and appropriate use of metric representations of space or topological knowledge of the environment. Spatial dimensions (2D vs. 3D), spatial scales (vista-scale vs. large-scale environments) and the abundance of visual landmarks critically affect navigation performance and behavior in healthy human subjects. Virtual reality (VR)-based navigation paradigms in stationary position have given insight into the major navigational strategies, namely egocentric (body-centered) and allocentric (world-centered), and the cerebral control of navigation. However, VR approaches are biased towards optic flow and visual landmark processing. This major limitation can be overcome to some extent by increasingly immersive and realistic VR set-ups (including large-screen projections, eye tracking and use of head-mounted camera systems). However, the highly immersive VR settings are difficult to apply particularly to older subjects and patients with neurological disorders because of cybersickness and difficulties with learning and conducting the tasks. Therefore, a need for the development of novel spatial tasks in real space exists, which allows a synchronous analysis of navigational behavior, strategy, visual explorations and navigation-induced brain activation patterns. This review summarizes recent findings from real space navigation studies in healthy subjects and patients with different cognitive and sensory neurological disorders. Advantages and limitations of real space navigation testing and different VR-based navigation paradigms are discussed in view of potential future applications in clinical neurology

Coronary artery calcification score in migraine patients

Epidemiological studies have shown an increased risk of cardiovascular events in migraineurs. The pathophysiological mechanisms of this observation remain largely unknown. Recent genetic and epidemiologic studies suggest, that atherosclerosis might be the overlapping pathophysiological mechanism in migraine and coronary heart disease. The aim of the present study was to evaluate if the increased cardiovascular risk in migraineurs is attributed to an increased coronary artery calcification. For this the coronary artery calcium score was assessed by computed tomography of the heart in 1.437 patients of which 337 were migraineurs. All patients had a similar cardiovascular risk profile, so that the risk for coronary calcifications could be considered similar between migraineurs and non-migraineurs. The results showed no significant differences in the amount of coronary calcifications in patients with or without migraine. This suggests that a more pronounced coronary artery calcification, as a surrogate marker of coronary atherosclerosis, does not underlie the increased cardiovascular risk in migraineurs. A distinct common pathophysiological mechanism in migraine and coronary heart disease such as endothelial dysfunction or vasospasm should be discussed instead. However, it has to be considered, that the coronary artery calcification score does not indicate the total risk of atherosclerotic changes in the coronary arteries

Towards a Time-predictable Dual-Issue Microprocessor: The Patmos Approach

Current processors are optimized for average case performance, often leading to a high worst-case execution time (WCET). Many architectural features that increase the average case performance are hard to be modeled for the WCET analysis. In this paper we present Patmos, a processor optimized for low WCET bounds rather than high average case performance. Patmos is a dual-issue, statically scheduled RISC processor. The instruction cache is organized as a method cache and the data cache is organized as a split cache in order to simplify the cache WCET analysis. To fill the dual-issue pipeline with enough useful instructions, Patmos relies on a customized compiler. The compiler also plays a central role in optimizing the application for the WCET instead of average case performance

Clinical evaluation of the bed cycling test

Objective: Additionally to the forearm rolling test to detect mild unilateral upper limb dysfunction, the bed cycling test (BCT) for detection of mild to moderate lower limb dysfunction was developed, evaluated and compared to the leg holding test. Methods: In a prospective observer-blinded study, 60 patients with MRI/CT-proven focal cerebral hemisphere lesions and a mild to moderate unilateral paresis of the lower limb (graduated MRC 3-4/5), and 60 control persons with normal imaging were examined and filmed. Nine observers blinded to the diagnosis evaluated these videos. The sensitivity, specificity and the positive and negative predictive values of the clinical tests were analyzed. Results: The observers gave a correct evaluation of BCT in 35.5% of all patients with focal cerebral lesions compared to 26.0% for the leg holding test. On the other hand, observers had false negative results in 29.1% of cases with BCT and 44.7% with leg holding test. In 36.7% of patients, only BCT was pathological while leg holding test was unremarkable. The sensitivity of the combination of both tests was 0.68 (95% CI 0.61-0.75). The BCT is more sensitive (64.3%) than leg holding test (46.2%) while the specificity of leg holding test (85.6%) is higher than of BCT (70.1%) to detect a cerebral lesion affecting the lower limb. The inter-rater variability is high with no differences comparing different types of clinical experience. Conclusions: The BCT is a useful additional clinical bedside test to detect subtle unilateral cerebral lesions. The BCT is easy to perform and can be added to the routine neurological examination

Clinical and genetic features of amyotrophic lateral sclerosis patients with C9orf72 mutations

An expansion of the GGGGCC hexanucleotide in the non-coding region of C9orf72 represents the most common cause of familial amyotrophic lateral sclerosis. The objective was to describe and analyse the clinical and genetic features of amyotrophic lateral sclerosis patients with C9orf72 mutations in a large population. Between November 2011 and December 2020, clinical and genetic characteristics of n = 248 patients with amyotrophic lateral sclerosis carrying C9orf72 mutations were collected from the clinical and scientific network of German motoneuron disease centres. Clinical parameters included age of onset, diagnostic delay, family history, neuropsychological examination, progression rate, phosphorylated neurofilament heavy chain levels in CSF and survival. The number of repeats was correlated with the clinical phenotype. The clinical phenotype was compared to n = 84 patients with SOD1 mutations and n = 2178 sporadic patients without any known disease-related mutations. Patients with C9orf72 featured an almost balanced sex ratio with 48.4% (n = 120) women and 51.6% (n = 128) men. The rate of 33.9% patients (n = 63) with bulbar onset was significantly higher compared to sporadic (23.4%, P = 0.002) and SOD1 patients (3.1%, P < 0.001). Of note, 56.3% (n = 138) of C9orf72, but only 16.1% of SOD1 patients reported a negative family history (P < 0.001). The GGGGCC hexanucleotide repeat length did not influence the clinical phenotypes. Age of onset (58.0, interquartile range 52.0-63.8) was later compared to SOD1 (50.0, interquartile range 41.0-58.0;P < 0.001), but earlier compared to sporadic patients (61.0, interquartile range 52.0-69.0;P = 0.01). Median survival was shorter (38.0 months) compared to SOD1 (198.0 months, hazard ratio 1.97, 95% confidence interval 1.34-2.88;P < 0.001) and sporadic patients (76.0 months, hazard ratio 2.34, 95% confidence interval 1.64-3.34;P < 0.001). Phosphorylated neurofilament heavy chain levels in CSF (2880, interquartile range 1632-4638 pg/ml) were higher compared to sporadic patients (1382, interquartile range 458-2839 pg/ml;P < 0.001). In neuropsychological screening, C9orf72 patients displayed abnormal results in memory, verbal fluency and executive functions, showing generally worse performances compared to SOD1 and sporadic patients and a higher share with suspected frontotemporal dementia. In summary, clinical features of patients with C9orf72 mutations differ significantly from SOD1 and sporadic patients. Specifically, they feature a more frequent bulbar onset, a higher share of female patients and shorter survival. Interestingly, we found a high proportion of patients with negative family history and no evidence of a relationship between repeat lengths and disease severity. Wiesenfarth et al. report that amyotrophic lateral sclerosis patients with C9orf72 mutations differ significantly from sporadic patients and SOD1 gene carriers, including a higher share of bulbar onset, female patients, more severe neuropsychological deficits and shorter survival. No evidence of a relationship between repeat lengths and disease severity was found

Wavelet analysis of stratosphere gravity wave packets over Macquarie Island 1. Wave parameters

We describe a technique to detect gravity wave packets in high-resolution radiosonde soundings of horizontal wind and temperature. The vertical profiles of meridional and zonal wind speeds are transformed using the Morlet wavelet, and regions of high wind variance in height-wavenumber space are identified as gravity wave packets. Application of the Stokes parameter analysis to horizontal wind and temperature profiles of the reconstructed wave packets yields the wave parameters. The technique was applied to twice-daily radiosonde launches at Macquarie Island (55°S, 159°E) between 1993 and 1995. A strong seasonal cycle in the total wave variance was found, with a maximum in winter. The amount of wave energy propagating downward from the upper stratosphere also maximized in winter. Waves propagated predominately toward the southwest in winter, but in summer propagation directions were approximately isotropic. The intrinsic frequencies were close to the inertial frequency, and the waves had inferred horizontal wavelengths of several hundred kilometers.Florian Zink and Robert A. Vincen

Static Routing in Symmetric Real-Time Network-on-Chips

With the rising number of cores on a single chip the question on how to organize the communication among those cores becomes more and more relevant. A common solution is to use a network-on-chip (NoC) that provides communication bandwidth, routing, and arbitration among the cores. The use of NoCs in real-time systems is problematic, since the shared network and all cores connected to it have to be analyzed to derive time bounds of real-time tasks. We propose to use a statically scheduled, time-divisionmultiplexed NoC design that allows a decoupled analysis of individual real-time tasks. Our network provides virtual circuits between all cores. These virtual circuits are implemented by delivering messages periodically on a static, fixed routing schedule. Since the routing does not change, it can be pre-computed offline. This work focuses on the computation of routing schedules for symmetric NoC topologies, e.g., torus and hypercube. Due to the symmetry, the all-to-all communication can be modeled via simplified communication patterns that are concurrently processed by all routers. The scheduling problem is solved by a heuristic that tries to maximize the overlap of active patterns. Our experiments show that, for larger networks, our heuristic yields schedule lengths that are only 15 % to 20 % longer than theoretical lower bounds. Categories and Subject Descriptors C.3 [Special-Purpose and Application-Based Systems]: Real-time and embedded systems

Support for the logical execution time model on a time-predictable multicore processor

The logical execution time (LET) model increases the compositionality of real-time task sets. Removal or addition of tasks does not influence the communication behavior of other tasks. In this work, we extend a multicore operating system running on a time-predictable multicore processor to support the LET model. For communication between tasks we use message passing on a time-predictable network-on-chip to avoid the bottleneck of shared memory. We report our experiences and present results on the costs in terms of memory and execution time. </jats:p

Embedded JIT Compilation with CACAO on YARI

Java is one of the most popular programming languages for the development of portable workstation and server applications available today. Because of its clean design and typesafety, it is also becoming attractive in the domain of embedded systems. Unfortunately, the dynamic features of the language and its rich class library cause considerable overhead in terms of runtime and memory consumption. Efficient techniques to implement Java virtual machines that are suitable for use in resource constrained environments are thus needed. In this work we present a solution for very restricted environments based on CACAO. CACAO is a just-intime compiling virtual machine implementation, combining high speed and small size. We have modified the original version of CACAO to run without an underlying operating system within only 1 MB of memory. In addition we present a new technique to selectively compile methods during the initialization phase of real-time Java applications to prevent unwanted interaction between dynamic compilation and critical tasks. Furthermore we present the YARI soft-core as the execution platform of CACAO within an field-programmable gate array. We compare our implementation with two well known Java processors, JOP and Sun’s picoJava-II, on the same technology. Although JOP achieves a higher clock frequency and picoJava-II occupies nearly 4 times the resource of YARI, our solution is capable to outperform both of them by a factor of up to 2.8 and 2.2 respectively.