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

A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials

There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds' activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan

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

Towards an integrated clinical framework for patient with shoulder pain

Background: Shoulder pain (SP) represents a common musculoskeletal condition that requires physical therapy care. Along the years, the usual evaluation strategies based on clinical tests and diagnostic imaging has been challenged. Clinical tests appear unable to clearly identify the structures that generated pain and interpretation of diagnostic imaging is still controversial. The current patho-anatomical diagnostic categories have demonstrated poor reliability and seem inadequate for the SP treatment. Objectives: The present paper aims to (1) describe the different proposals of clinical approach to SP currently available in the literature; to (2) integrate these proposals in a single framework in order to help the management of SP. Conclusion: The proposed clinical framework, based on a bio-psychosocial vision of health, integrates symptoms characteristics, pain mechanisms and expectations, preferences and psychosocial factors of patients that may guide physiotherapist to make a diagnostic triage and to choose the right treatment for the individual patient

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

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

A Specialized Processor for Track Reconstruction at the LHC Crossing Rate

We present the results of an R&D study of a specialized processor capable of precisely reconstructing events with hundreds of charged-particle tracks in pixel detectors at 40 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 by studies of the processing of visual images by the brain as it happens in nature. We find that high-quality tracking in large detectors is possible with sub-$\mu$s latencies when this algorithm is implemented in modern, high-speed, high-bandwidth FPGA devices. This opens a possibility of making track reconstruction happen transparently as part of the detector readout.Comment: Presented by G.Punzi at the conference on "Instrumentation for Colliding Beam Physics" (INSTR14), 24 Feb to 1 Mar 2014, Novosibirsk, Russia. Submitted to JINST 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

Development and Performance of RFD Crab Cavity Prototypes for HL-LHC AUP

The US will be contributing to the HL-LHC upgrade at CERN with the fabrication and qualification of RFD crabbing cavities in the framework of the HL-LHC Accelerator Upgrade Project (AUP) managed by Fermilab. AUP received Critical Decision 3 (CD-3) approval by DOE in December 2020 launching the project into the production phase. The electro-magnetic design of the cavity was inherited from the LHC Accelerator Research Program (LARP) but needed to be revised to meet new project requirements and to prevent issues encountered during beam tests performed at CERN in the R&D phase. Two prototype cavities were manufactured in industry and cold tested. Challenges specific to the RFD cavity were the stringent interface tolerances, the pole symmetry, and the higher-order-mode impedance spectrum. Chemical processing and heat treatments were performed initially at FNAL/ANL and are now being transferred to industry for the production phase. HOM dampers are manufactured and validated by JLAB. A summary of cold test results with and without HOM dampers is presented.Comment: 21st International Conference on RF Superconductivity (SRF23