Driving with Homonymous Visual Field Defects: Driving Performance and Compensatory Gaze Movements

Aim of this pilot study was to assess the driving performance and its relationship to the visual search behavior, i.e., eye and head movements, of patients with homonymous visual field defects (HVFDs) in comparison to healthy-sighted subjects during a simulated driving test. Eight HVFD patients and six healthy-sighted age- and gender-matched control subjects underwent a 40-minute driving test with nine hazardous situations. Eye and head movements were recorded during the drive. Four out of eight patients passed the driving test and showed a driving performance similar to that of the control group. One control group subject failed the test. Patients who passed the test showed an increased number of head and eye movements. Patients who failed the test showed a rightwards-bias in average lane position, probably in an attempt to maximize the safety margin to oncoming traffic. Our study supports the hypothesis that a considerable subgroup of subjects with HVFDs show a safe driving behavior, because they adapt their viewing behavior by increased visual scanning

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Ecological Ontologies.

This issue explores multiple worlds and the multifarious being and becoming of and in worlds, revealing ecological moments of engagement with the environment to scrutinize power dimensions, structural inequalities, and inter­pretational sovereignty over knowledge production and the constitution and forming of worlds. The issue brings together ethnographic contributions from anthropology and STS that critically elaborate on a concept of the environment as deeply entangled with multiple ways of being within plural temporalities in multiple localities. In doing so, the contributions urge us to pay attention to a relational otherwise that pivots in transversal (research-)fields to hint at ways to rebel against ontonorms and to intervene politically in predominant human-environment relationships.Diese Ausgabe untersucht multiple Welten und das vielfältige Sein und Werden von und in Welten. Die ethnographischen Studien aus dem Bereich der ontologischen Wende(n) enthüllen ökologische Momente der Auseinandersetzung mit der Umwelt und erforschen dabei Dimensionen von Macht, Ungleichheitsstrukturen und Deutungshoheit über Wissensproduktion sowie über die Konstitution und Formierung von Welten. Die Ausgabe versammelt Beiträge aus Anthropologie und STS, die auf kritische Weise ein Konzept von Umwelt als tief verwoben und verstrickt mit multiplen Seinsweisen im Rahmen pluraler Zeitlichkeiten in vielfältigen Lokalitäten herausarbeiten. Dabei fordern die Beiträge auf ein relationales Anderssein zu achten, das sich in transversalen (Forschungs-)Feldern kristallisiert und Hinweise darauf gibt, wie ein Auflehnen gegen Ontonormen aussehen kann und wie sich in dominanten Mensch-Umwelt-Beziehungen intervenieren lässt.Peer Reviewe

Quantitative sensory testing and norepinephrine levels in REM sleep behaviour disorder – a clue to early peripheral autonomic and sensory dysfunction?

Introduction!#!Studies have reported autonomic impairment in patients with idiopathic REM sleep behaviour disorder (iRBD), which is considered a prodromal stage of alpha-synucleinopathies. It is still debated whether central or peripheral pathologies are first manifestations of alpha-synucleinopathies. This study aimed to characterize autonomic and somatosensory function in iRBD patients.!##!Methods!#!This cross-sectional prospective case-control study included 17 iRBD patients (mean age 66.3 ± 9.2 years) and 16 healthy controls (HCs, 66.6 ± 11.3 years). Quantitative sensory testing, neurological and neuropsychological assessments, norepinephrine blood plasma levels, tilt table examination with orthostatic blood pressure, and heart rate variability were carried out. Longitudinal data of 10 iRBD patients, including neurological, neuropsychological, and tilt table examination, were assessed.!##!Results!#!iRBD patients more frequently presented with orthostatic dysfunction than HCs (70.6% vs. 6.3%, p < 0.0001). Supine norepinephrine plasma levels were normal, but lower in iRBD (249.59 ± 99.78 pg/ml iRBD, 354.13 ± 116.38 pg/ml HCs, p < 0.05). Quantitative sensory testing revealed impaired cold (CDT) and vibration detection thresholds (VDT) on the foot in iRBD (CDT foot iRBD - 1.24 ± 0.31, HCs - 9.89E-17 ± 0.25, VDT iRBD - 1.11 ± 0.47, HCs - 1.46E-16 ± 0.25, p < 0.05). Cold detection thresholds differed between the foot and hand among iRBD patients (foot - 1.24 ± 0.31, hand - 0.56 ± 0.25, p < 0.05). Longitudinal data revealed an increase in maximum systolic and diastolic orthostatic blood pressure changes and a decrease in the Valsalva ratio in the follow-up group (p < 0.05).!##!Conclusion!#!This study revealed autonomic dysfunction with somatosensory impairment, and decreased norepinephrine levels in iRBD, which may serve as a possible prodromal marker for developing alpha-synucleinopathy

Brain imaging findings in idiopathic REM sleep behavior disorder (RBD) - A systematic review on potential biomarkers for neurodegeneration

Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the loss of physiological atonia of skeletal muscles with abnormal behavior during dream sleep. RBD may be the initial manifestation of neurodegenerative diseases, particularly of α-synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, gauging the individual risk of subsequent phenoconversion and making assumptions on the type of disease that may subsequently follow RBD is challenging. Over the past years, a growing number of studies have sought to establish reliable neuroimaging markers to detect neurodegenerative brain changes in RBD subjects at the earliest possible stage.The present review summarizes recent advances in brain imaging in RBD and provides recommendations for the application of currently available structural and functional neuroimaging modalities to monitor disease progression and risk of subsequent phenoconversion.Further imaging research applying multimodal approaches is encouraged to enhance accuracy of prognoses. Additionally, more longitudinal studies are warranted to validate findings from cross-sectional studies on RBD progression and risk of subsequent phenoconversion. Aside from enabling reliable prognoses on a single-subject-level in the near future, this might give further insight into RBD pathophysiology, and finally augment the development of intervention strategies and disease-modifying therapies

Comparison of the horizontal gaze distribution (HGD) towards the central 20° area of the visual field between patients who passed (Pf) and patients who failed (Pf); glaucoma patients who passed (GPp) and glaucoma patients who failed (GPf); and between patients with right-sided HVFDs who passed (HRp), with left-sided HVFDs who passed (HLp), and patients with HVFDs who failed (HPf).

<p>Comparison of the horizontal gaze distribution (HGD) towards the central 20° area of the visual field between patients who passed (Pf) and patients who failed (Pf); glaucoma patients who passed (GPp) and glaucoma patients who failed (GPf); and between patients with right-sided HVFDs who passed (HRp), with left-sided HVFDs who passed (HLp), and patients with HVFDs who failed (HPf).</p

(a) A participant, wearing the mobile eye-tracking head unit; (b) First camera recording the road scene during the drive; (c) Second camera recording the driver during the drive; (d) Calibration points; (e) Scene marker used for calibration.

<p>The subject has given written informed consent, as outlined in the PLOS consent form, to publication of their photograph.</p