Direct and indirect effects of attention and visual function on gait impairment in Parkinson’s disease: influence of task and turning

Gait impairment is a core feature of Parkinson’s disease (PD) which has been linked to cognitive and visual deficits, but interactions between these features are poorly understood. Monitoring saccades allows investigation of real-time cognitive and visual processes and their impact on gait when walking. This study explored; 1) saccade frequency when walking under different attentional manipulations of turning and dual-task; and 2) direct and indirect relationships between saccades, gait impairment, vision and attention. Saccade frequency (number of fast eye-movements per-second) was measured during gait in 60 PD and 40 age-matched control participants using a mobile eye-tracker. Saccade frequency was significantly reduced in PD compared to controls during all conditions. However, saccade frequency increased with a turn and decreased under dual-task for both groups. Poorer attention directly related to saccade frequency, visual function and gait impairment in PD, but not controls. Saccade frequency did not directly relate to gait in PD, but did in controls. Instead, saccade frequency and visual function deficit indirectly impacted gait impairment in PD, which was underpinned by their relationship with attention. In conclusion, our results suggest a vital role for attention with direct and indirect influences on gait impairment in PD. Attention directly impacted saccade frequency, visual function and gait impairment in PD, with connotations for falls. It also underpinned indirect impact of visual and saccadic impairment on gait. Attention therefore represents a key therapeutic target that should be considered in future research

Production and detection of atomic hexadecapole at Earth's magnetic field

Anisotropy of atomic states is characterized by population differences and coherences between Zeeman sublevels. It can be efficiently created and probed via resonant interactions with light, the technique which is at the heart of modern atomic clocks and magnetometers. Recently, nonlinear magneto-optical techniques have been developed for selective production and detection of higher polarization moments, hexadecapole and hexacontatetrapole, in the ground states of the alkali atoms. Extension of these techniques into the range of geomagnetic fields is important for practical applications. This is because hexadecapole polarization corresponding to the $\Delta M=4$ Zeeman coherence, with maximum possible $\Delta M$ for electronic angular momentum $J=1/2$ and nuclear spin $I=3/2$, is insensitive to the nonlinear Zeeman effect (NLZ). This is of particular interest because NLZ normally leads to resonance splitting and systematic errors in atomic magnetometers. However, optical signals due to the hexadecapole moment decline sharply as a function of magnetic field. We report a novel method that allows selective creation of a macroscopic long-lived ground-state hexadecapole polarization. The immunity of the hexadecapole signal to NLZ is demonstrated with F=2 $^{87}$Rb atoms at Earth's field.Comment: 4 pages, 5 figure

Measurement of Dielectric Suppression of Bremsstrahlung

In 1953, Ter-Mikaelian predicted that the bremsstrahlung of low energy photons in a medium is suppressed because of interactions between the produced photon and the electrons in the medium. This suppression occurs because the emission takes place over on a long distance scale, allowing for destructive interference between different instantaneous photon emission amplitudes. We present here measurements of bremsstrahlung cross sections of 200 keV to 20 MeV photons produced by 8 and 25 GeV electrons in carbon and gold targets. Our data shows that dielectric suppression occurs at the predicted level, reducing the cross section up to 75 percent in our data.Comment: 11 pages, format is postscript file, gzip-ed, uuencode-e

'Staying safe' – A narrative review of falls prevention in people with Parkinson’s -'PDSAFE'

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.Background: Parkinson's disease demonstrates a spectrum of motor and non-motor symptoms. Falling is common and disabling. Current medical management shows minimal impact to reduce falls, or fall related risk factors such as deficits in gait, strength and postural instability. Despite evidence supporting rehabilitation in reducing fall risk factors, the most appropriate intervention to reduce overall fall rate remains inconclusive. This paper aims to 1) synthesise current evidence and conceptual models of falls rehabilitation in Parkinson's in a narrative review; and based on this evidence 2) introduce the treatment protocol used in the falls prevention, multi-centre clinical trial 'PDSAFE'. Method: Search of four bibliographic databases using the terms ‘Parkinson*’ and ‘Fall*’ combined with each of the following; ‘Rehab*, Balanc*, Strength*, Strateg*and Exercis*' and a framework for narrative review was followed. 3557 papers were identified, 416 were selected for review. The majority report the impact of rehabilitation on isolated fall risk factors. Twelve directly measure the impact on overall fall rate. Discussion: Results were used to construct a narrative review with conceptual discussion based on the 'International Classification of Functioning’, leading to presentation of the 'PDSAFE' intervention protocol. Conclusion: Evidence suggests training single, fall risk factors may not affect overall fall rate. Combining with behavioural and strategy training in a functional, personalised multi-dimensional model, addressing all components of the ‘International Classification of Functioning’ is likely to provide a greater influence on falls reduction. 'PDSAFE' is a multi-dimensional, physiotherapist delivered, individually tailored, progressive, home-based programme. It is designed with a strong evidence based approach and illustrates a model for the clinical delivery of the conceptual theory discussed.This project was funded by the National Institute for Health Research Health Technologies Assessment programme (project number 10/57/21). VG is supported by the National Institute of Health Research Collaboration for Applied Health Research and Care South West Peninsula.

Germline Maintenance Through the Multifaceted Activities of GLH/Vasa in

Vasa homologs are ATP-dependent DEAD-box helicases, multipotency factors, and critical components that specify and protect the germline. They regulate translation, amplify piwi-interacting RNAs (piRNAs), and act as RNA solvents; however, the limited availability of mutagenesis-derived alleles and their wide range of phenotypes have complicated their analysis. Now, with clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), these limitations can be mitigated to determine why protein domains have been lost or retained throughout evolution. Here, we define the functional motifs of GLH-1/Vasa i

Experimental Vacuum Squeezing in Rubidium Vapor via Self-Rotation

We report the generation of optical squeezed vacuum states by means of polarization self-rotation in rubidium vapor following a proposal by Matsko et al. [Phys. Rev. A 66, 043815 (2002)]. The experimental setup, involving in essence just a diode laser and a heated rubidium gas cell, is simple and easily scalable. A squeezing of 0.85+-0.05 dB was achieved

Bremsstrahlung Suppression due to the LPM and Dielectric Effects in a Variety of Materials

The cross section for bremsstrahlung from highly relativistic particles is suppressed due to interference caused by multiple scattering in dense media, and due to photon interactions with the electrons in all materials. We present here a detailed study of bremsstrahlung production of 200 keV to 500 MeV photons from 8 and 25 GeV electrons traversing a variety of target materials. For most targets, we observe the expected suppressions to a good accuracy. We observe that finite thickness effects are important for thin targets.Comment: 52 pages, 13 figures (incorporated in the revtex LaTeX file

Toward a regulatory qualification of real-world mobility performance biomarkers in Parkinson’s patients using Digital Mobility Outcomes

Wearable inertial sensors can be used to monitor mobility in real-world settings over extended periods. Although these technologies are widely used in human movement research, they have not yet been qualified by drug regulatory agencies for their use in regulatory drug trials. This is because the first generation of these sensors was unreliable when used on slow-walking subjects. However, intense research in this area is now offering a new generation of algorithms to quantify Digital Mobility Outcomes so accurate they may be considered as biomarkers in regulatory drug trials. This perspective paper summarises the work in the Mobilise-D consortium around the regulatory qualification of the use of wearable sensors to quantify real-world mobility performance in patients affected by Parkinson’s Disease. The paper describes the qualification strategy and both the technical and clinical validation plans, which have recently received highly supportive qualification advice from the European Medicines Agency. The scope is to provide detailed guidance for the preparation of similar qualification submissions to broaden the use of real-world mobility assessment in regulatory drug trials