Noise in multiple sclerosis: unwanted and necessary

As our knowledge about the etiology of multiple sclerosis (MS) increases, deterministic paradigms appear insufficient to describe the pathogenesis of the disease, and the impression is that stochastic phenomena (i.e. random events not necessarily resulting in disease in all individuals) may contribute to the development of MS. However, sources and mechanisms of stochastic behavior have not been investigated and there is no proposed framework to incorporate nondeterministic processes into disease biology. In this report, we will first describe analogies between physics of nonlinear systems and cell biology, showing how small-scale random perturbations can impact on large-scale phenomena, including cell function. We will then review growing and solid evidence showing that stochastic gene expression (or gene expression “noise”) can be a driver of phenotypic variation. Moreover, we will describe new methods that open unprecedented opportunities for the study of such phenomena in patients and the impact of this information on our understanding of MS course and therapy

Exploring the structural relationship between interviewer and self-rated affective symptoms in Huntington’s disease

This study explores the structural relationship between self-report and interview measures of affect in Huntington’s disease. The findings suggest continued use of both to recognize the multidimensionality within a single common consideration of distress

Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis

Introduction: The age of diagnosis of Huntington's disease (HD) varies among individuals with the same HTT CAG-repeat expansion size. We investigated whether early-life events, like perinatal insults or neurodevelopmental disorders, influence the diagnosis age. Methods: We used data from 13,856 participants from REGISTRY and Enroll-HD, two large international multicenter observational studies. Disease-free survival analyses of mutation carriers with an HTT CAG repeat expansion size above and including 36 were computed through Kaplan-Meier estimates of median time until an HD diagnosis. Comparisons between groups were computed using a Cox proportional hazard survival model adjusted for CAG-repeat expansion length. We also assessed whether the group effect depended on gender and the affected parent. Results: Insults in the perinatal period were associated with an earlier median age of diagnosis of 45.00 years (95%CI: 42.07–47.92) compared to 51.00 years (95%CI: 50.68–51.31) in the reference group, with a CAG-adjusted hazard ratio of 1.61 (95%CI: 1.26–2.06). Neurodevelopmental disorders were also associated with an earlier median age of diagnosis than the reference group of 47.00 years (95% CI: 43.38–50.62) with a CAG-adjusted hazard ratio of 1.42 (95%CI: 1.16–1.75). These associations did not change significantly with gender or affected parent. Conclusions: These results, derived from large observational datasets, show that perinatal insults and neurodevelopmental disorders are associated with earlier ages of diagnosis of magnitudes similar to the effects of known genetic modifiers of HD. Given their clear temporal separation, these early events may be causative of earlier HD onset, but further research is needed to prove causation

Simulation and performance of an artificial retina for 40 MHz track reconstruction

We present the results of a detailed simulation of the artificial retina pattern-recognition algorithm, designed to reconstruct events with hundreds of charged-particle tracks in pixel and silicon detectors at LHCb with LHC crossing frequency of $40\,\rm MHz$. Performances of the artificial retina algorithm are assessed using the official Monte Carlo samples of the LHCb experiment. We found performances for the retina pattern-recognition algorithm comparable with the full LHCb reconstruction algorithm.Comment: Final draft of WIT proceedings modified according to JINST referee's comment

The artificial retina for track reconstruction at the LHC crossing rate

We present the results of an R&D study for a specialized processor capable of precisely reconstructing events with hundreds of charged-particle tracks in pixel and silicon strip detectors at $40\,\rm MHz$, thus suitable for processing LHC events at the full crossing frequency. For this purpose we design and test a massively parallel pattern-recognition algorithm, inspired to the current understanding of the mechanisms adopted by the primary visual cortex of mammals in the early stages of visual-information processing. The detailed geometry and charged-particle's activity of a large tracking detector are simulated and used to assess the performance of the artificial retina algorithm. We find that high-quality tracking in large detectors is possible with sub-microsecond latencies when the algorithm is implemented in modern, high-speed, high-bandwidth FPGA devices.Comment: 3 pages, 3 figures, ICHEP14. arXiv admin note: text overlap with arXiv:1409.089

Custom-made 3d-printed implants as novel approach to reconstructive surgery after oncologic resection in pediatric patients

Recently, custom-made 3D-printed prostheses have been introduced for limb salvage surgery in adult patients, but their use has not been described in pediatric patients. A series of 11 pediatric patients (mean age 10.8 years; range 2–13) with skeletal tumors treated with custom-made implants for the reconstruction of bony defects is described. Patients were followed up every 3 months. Functional results were evaluated by the Musculoskeletal Tumor Society Score (MSTS) for upper and lower limbs. The mean follow-up was 25.7 months (range 14–44). Three patients died after a mean of 19.3 months postoperatively—two because of disease progression and the other from a previous malignancy. Three patients experienced complications related to soft tissues. One patient required device removal, debridement, and antibiotic pearls for postoperative infection. Partial osseointegration between grafts and host bone was observed within a mean of 4 months. At the final follow-up, mean MSTS score was 75%. 3D prostheses may yield biological advantages due to possible integration with the host bone and also through the use of vascularized flaps. Further research is warranted

First prototype of a silicon tracker using an artificial retina for fast track finding

We report on the R\&D for a first prototype of a silicon tracker based on an alternative approach for fast track finding. The working principle is inspired from neurobiology, in particular by the processing of visual images by the brain as it happens in nature. It is based on extensive parallelisation of data distribution and pattern recognition. In this work we present the design of a practical device that consists of a telescope based on single-sided silicon detectors; we describe the data acquisition system and the implementation of the track finding algorithms using available digital logic of commercial FPGA devices. Tracking performance and trigger capabilities of the device are discussed along with perspectives for future applications.Comment: 9 pages, 7 figures, Technology and Instrumentation in Particle Physics 2014 (TIPP 2014), conference proceeding

The artificial retina processor for track reconstruction at the LHC crossing rate

We present results of an R&D study for a specialized processor capable of precisely reconstructing, in pixel detectors, hundreds of charged-particle tracks from high-energy collisions at 40 MHz rate. We apply a highly parallel pattern-recognition algorithm, inspired by studies of the processing of visual images by the brain as it happens in nature, and describe in detail an efficient hardware implementation in high-speed, high-bandwidth FPGA devices. This is the first detailed demonstration of reconstruction of offline-quality tracks at 40 MHz and makes the device suitable for processing Large Hadron Collider events at the full crossing frequency.Comment: 4th draft of WIT proceedings modified according to JINST referee's comments. 10 pages, 6 figures, 2 table