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Background: Immunotherapies targeting α-synuclein aim to limit its extracellular spread in the brain and prevent progression of pathology in Parkinson's disease (PD). PD03A is a specific active immunotherapy (SAIT) involving immunization with a short peptide formulation., Objective: This phase 1 study characterized the safety and tolerability of PD03A in patients with early PD. A key secondary objective was to evaluate immunological activity following immunization., Methods: This was a phase 1 study of two different doses of PD03A versus placebo in PD patients. Patients were randomized (1:1:1) to receive four priming plus one booster vaccination of PD03A 15μg, PD03A 75μg or placebo and were followed for 52 weeks., Results: Overall, 36 patients were randomized, of which 35 received five immunizations and completed the study. All patients experienced at least one adverse event. Transient local injection site reactions affected all but two patients; otherwise most AEs were considered unrelated to study treatment. A substantial IgG antibody response against PD03 was observed with a maximum titer achieved at Week-12. Differences in titers between both active groups versus placebo were statistically significant from the second immunization at Week-8 until Week-52., Conclusion: The safety profile and positive antibody response of PD03A supports the further development of active immunotherapeutic approaches for the treatment of PD.

Introduction: Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP parkinsonism, yet few data exist on the usefulness of these markers in early disease stages., Methods: The pons-to-midbrain area ratio (P/M) and the Magnetic Resonance Parkinsonism Index (MRPI) as well as new indices, termed P/M2.0 and MRPI2.0, multiplying the former by a ratio of the third ventricle (3rdV) width/frontal horns (FH) width, were calculated on T1-weighted images in 84 patients with clinically unclassifiable neurodegenerative parkinsonism (CUP) at the time of imaging. Areas under the curve (AUCs) of these markers for predicting future PSP was determined. The final clinical diagnosis was made after at least 24 months of follow-up., Results: Final diagnosis was Parkinson's disease in 55 patients, multiple system atrophy in 12 cases, and PSP in 17. At baseline imaging, patients with a final PSP diagnosis had significantly higher MRPI, P/M, MRPI2.0 and P/M2.0 values compared to the other groups. AUCs in discriminating between future PSP and non-PSP parkinsonism were 0.91 for both the P/M and the MRPI and 0.98 for the P/M2.0 and the MRPI2.0., Conclusions: Brainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. Consistent with the underlying pathology in PSP, our study suggests that inclusion of 3 rd V width makes P/M2.0 and MRPI2.0 more accurate in diagnosing early stage PSP patients than the P/M and MRPI., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: We aimed to investigate costly punishment in patients with Huntington's disease (HD)., Background: HD is an autosomal dominant neurodegenerative disease with motor, cognitive, and psychiatric symptoms. As neuropsychiatric abnormalities often precede motor symptoms, we wanted to assess whether costly punishment is part of the neuropsychological profile of patients with HD., Methods: A total of 40 non-demented subjects were prospectively enrolled in this study with a between-subject design comparing manifest HD patients (n = 18) to healthy controls (HC; n = 22). All participants performed 8 rounds of a costly punishment task, in which money was shared unevenly in 5 rounds or in a fair manner in the remaining 3 rounds. Participants then had to decide whether they wanted to punish the trustee. Furthermore, all participants underwent neuropsychological background tasks., Results: HD patients performed worse in the neuropsychological background tests compared to HC (all p values <0.05). Moreover, HD patients punished more often in fair (Wald χ2 = 5.03, p = 0.025) but not in unfair rounds (Wald χ2 = 1.63, p = 0.202)., Conclusions: Our results demonstrate increased costly punishment during fair conditions in HD patients. Whether this behaviour is due to a lack of recognition of social norms, an impairment in top-down inhibition, or an effect of antidopaminergic medication remains unclear., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Objective: We assessed frontal executive functions in patients with RLS/WED with and without augmentation and compared the results to healthy controls., Methods: We recruited 38 patients with RLS/WED. A total of 23 patients were treated with dopaminergic therapy and showed no signs of augmentation and 15 patients had a history of augmentation (AUG). Results were compared to 21 healthy controls. All individuals were assessed by the Frontal Assessment Battery (FAB) and the MMSE. Furthermore, impulsivity was assessed during a semi-structured interview., Results: Patients with AUG performed worse in the FAB than healthy controls and RLS/WED patients without AUG (p = 0.001, η 2  = 0.201). When we assessed the subtests of the FAB separately, we found a significant difference in the subtest assessing inhibitory control (p = 0.008, η 2  = 0.138)., Conclusions: Our findings suggest an impaired executive function in RLS/WED patients with augmentation compared to RLS/WED patients without augmentation and healthy controls. Long term neuroplastic changes within the prefrontal cortex may be the underlying cause for these results. However, further studies in a larger sample size and with a more extensive neuropsychological test battery are needed to confirm our preliminary results., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate cognitive flexibility in premanifest and manifest Huntington's disease (HD)., Background: HD is an autosomal dominant neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities with typical motor symptoms. In this study, we wanted to assess decision making in premanifest (pre-HD) and manifest HD patients., Methods: A total of 77 non-demented subjects including 29 pre-HD, 22 manifest HD patients, and 26 healthy controls (HC) were included. We stratified the pre-HD group based on their estimated years to disease onset into a far (FAR, n = 13) and a near (NEAR, n = 16) group. Furthermore, participants performed the Montreal cognitive assessment battery (MoCA), the trail making task part A and B (TMT A, TMT B), the Symbol digit modalities test (SDMT), and the beads task., Results: In the beads task, HD patients gathered less information than all other groups (all p-values < .001). Furthermore, the NEAR group gathered less information than the FAR group (p < .001) and HC (p = .001). There was no difference between the HC and the FAR group (p = 1.0). In the TMT and the SDMT, HD patients were slower than all other groups (all p-values < .01) but there were no other significant differences., Conclusions: Decision making with a higher degree of uncertainty may be an early neuropsychological sign to indicate the disease process prior to reaching criteria for motor diagnosis of HD., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: The objective of this study was to assess the efficacy and safety of nabilone, a synthetic tetrahydrocannabinol analogue, as a treatment for non-motor symptoms (NMS) in Parkinson's disease (PD)., Methods: This was a phase II placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal trial conducted at the Medical University Innsbruck. A random sample of 47 patients with PD with stable motor disease and disturbing NMS defined by a score of ≥4 points on the Movement Disorder Society - Unified PD Rating Scale-I (MDS-UPDRS-I) underwent open-label nabilone titration (0.25 mg once daily to 1 mg twice daily, phase I). Responders were randomized 1:1 to continue with nabilone or switch to placebo for 4 weeks (phase II). The primary efficacy criterion was the change of the MDS-UPDRS-I between randomization and week 4. Safety was analyzed in all patients who received at least one nabilone dose., Results: Between October 2017 and July 2019, 19 patients received either nabilone (median dose = 0.75 mg) or placebo. At week 4, mean change of the MDS-UPDRS-I was 2.63 (95% confidence interval [CI] 1.53 to 3.74, p = 0.002, effect size = 1.15) in the placebo versus 1.00 (95% CI -0.16 to 2.16, p = 0.280, effect size = 0.42) in the nabilone-group (difference: 1.63, 95% CI 0.09 to 3.18, p = 0.030, effect size = 0.66). Seventy-seven percent of patients had adverse events (AEs) during open-label titration, most of them were transient. In the double-blind phase, similar proportions of patients in each group had AEs (42% in the placebo group and 32% in the nabilone group). There were no serious AEs., Interpretation: Our results highlight the potential efficacy of nabilone for patients with PD with disturbing NMS, which appears to be driven by positive effects on anxious mood and night-time sleep problems., Trial Registry: ClinicalTrials.gov (NCT03769896) and EudraCT (2017-000192-86). ANN NEUROL 2020;88:712-722., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To assess emotional processing and alexithymia in patients with restless legs syndrome (RLS) with augmentation versus those who never had augmentation., Methods: We recruited 26 patients who had a history of augmentation (AUG), either current or past, 27 RLS patients treated with dopamine agonists who never had augmentation (RLS controls), and 21 healthy controls (HC). All participants were screened for impulse control disorders (ICDs). Alexithymia was assessed by means of the Toronto Alexithymia Scale - 20 (TAS-20). Facial emotion recognition was tested through an eye-tracking task. Furthermore, all participants performed neuropsychological tests assessing global cognitive status, impulsivity, anxiety, and depression., Results: ICD symptoms occurred more frequently in AUG patients than in RLS controls (P = 0.047). Patients with AUG scored higher on the TAS-20 (P = 0.007) and the attentional subdomain of an impulsivity scale (BIS-11; P = 0.015) compared to HC. Patients with AUG also performed worse on the facial emotion recognition task relative to RLS controls (P = 0.009) and HC (P = 0.003). We found a group difference for the time to first fixation and the fixation count in the mouth region (P = 0.019 and P = 0.021, respectively). There were no other differences in the eye tracking examination., Interpretation: This study showed evidence of poorer emotional processing in patients who had augmentation compared to RLS patients without augmentation and healthy controls. The altered exploration pattern of faces and the higher alexithymia scores suggest abnormalities in emotion processing in patients with augmentation., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: Cognitive impairment in multiple system atrophy (MSA) is common, but remain poorly characterized. We evaluated cognitive and behavioral features in MSA patients and assessed between-group differences for MSA subtypes and the effect of orthostatic hypotension (OH) on cognition., Methods: This retrospective study included 54 patients with clinical diagnosis of possible and probable MSA referred to the Department of Neurology at Medical University of Innsbruck between 2000 and 2018. Neurological work-up included comprehensive neuropsychological testing including Consortium to Establish a Registry for Alzheimer's Disease (CERAD-plus) test battery, Frontal Assessment Battery (FAB), digit span test (DST), clock drawing task (CLOX1), and Hospital Anxiety and Depression Scale (HADS-D)., Results: The mean MMSE score was 27.6 points. Overall, slight to moderate cognitive impairment was noted in up to 40% of patients, with predominant impairment of executive function and verbal memory. Patients with the cerebellar variant performed significantly worse than patients with the parkinsonian type (P < 0.05) in a screening of executive functions (FAB) and in phonemic verbal fluency. Depression and anxiety scores were elevated in 28% and 22% of MSA patients, respectively. Cognitive profile, depression, and anxiety levels were comparable between patients with and without OH., Interpretation: Cognitive deficits are relatively frequent in MSA and primarily affect executive functions and verbal memory. Future comparative studies including Parkinson dementia, Lewy body disease, and MSA cases with and without OH are required to elucidate disease-specific cognitive profiles in these synucleinopathies and to examine the influence of cardiovascular autonomic dysfunction on cognitive function in MSA., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Objective: The aim of this pilot study was to investigate change of olfactory functions in Huntington's disease (HD)., Background: HD is a neurodegenerative disease characterized by motor, cognitive, and behavioral abnormalities. There are several studies reporting olfactory dysfunction in manifest and some studies in premanifest HD carriers, and a recent neuropathological study demonstrated HD-specific protein aggregation in the anterior olfactory nucleus in HD patients. In this study, we wanted to assess olfactory functions as a possible early nonmotor symptom of HD mutation carriers without disease-specific motor symptoms and HD patients., Methods: All participants had genetic confirmed HD and were prospectively recruited during their routine control in a specialized outpatient clinic of the Medical University of Innsbruck, Department of Neurology, Austria. Healthy controls (HCs) were caregivers from patients. They were only included if they were younger than 70 years, scored more than 24/30 points on the Mini Mental State Examination, and had no other disease compromising olfactory function. Furthermore, all participants were tested on the Sniffin' sticks 16-items identification test., Results: We included 23 patients with manifest HD, 13 HD mutation carriers, and 19 HCs. Mutation carriers showed significant impaired odor identification compared to HCs (p < 0.001), as well as Huntington's patients compared with both mutation carriers (p = 0.003) and HCs (p < 0.001)., Conclusions: The results of this pilot study suggest that olfactory dysfunction may be an early nonmotor symptom of HD and could be a potential marker to assess disease progression., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Sarcopenia and frailty are found in up to one-third of the general elderly population. Both are associated with major adverse health outcomes such as nursing home placement, disability, decreased quality of life, and death. Data on the frequency of both syndromes in Parkinson's disease (PD), however, are very limited., Objective: We aimed to screen for sarcopenia and frailty in PD patients and to assess potential associations of both geriatric syndromes with demographic and clinical parameters as well as quality of life., Methods: In this observational, cross-sectional study, we included 104 PD patients from a tertiary center and 330 non-PD controls from a population-based cohort aged > 65 years. All groups were screened for sarcopenia using the SARC-F score and for frailty using the Clinical Frailty Scale of the Canadian Study of Health and Aging (CSHA CFS). Prevalence rates of sarcopenia and frailty were also assessed in 18 PD patients from a population-based cohort aged > 65 years. Moreover, PD patients from the tertiary center were evaluated for motor and non-motor symptoms, quality of life, and dependency., Results: The prevalence of sarcopenia was 55.8% (95% CI: 46.2-64.9%) in PD patients from the tertiary center and 8.2% (5.7-11.7%; p < 0.001) in non-PD controls. Frailty was detected in 35.6% (27.0-45.2%) and 5.2% (3.2-8.1%; p < 0.001). Prevalence rates for sarcopenia and frailty were 33.3% (16.1-56.4%; p = 0.004) and 22.2% (8.5-45.8%; p = 0.017) in the community-based PD sample. Both sarcopenia and frailty were significantly associated with longer disease duration, higher motor impairment, higher Hoehn and Yahr stages, decreased quality of life, higher frequency of falls, a higher non-motor symptom burden, institutionalization, and higher care levels in PD patients from a tertiary center compared to not affected PD patients (all p < 0.05)., Conclusions: Both frailty and sarcopenia are more common in PD patients than in the general community and are associated with a more adverse course of the disease. Future studies should look into underlying risk factors for the occurrence of sarcopenia and frailty in PD patients and into adequate management to prevent and mitigate them., (© 2018 S. Karger AG, Basel.)

Satellite-derived surface soil moisture data are available for the Arctic, but detailed validation is still lacking. Previous studies have shown low correlations between in situ and modeled data. It is hypothesized that soil temperature variations after soil thaw impact MetOp ASCAT satellite-derived surface soil moisture (SSM) measurements in wet tundra environments, as C band backscatter is sensitive to changes in dielectric properties. We compare in situ measurements of water content within the active layer at four sites across the Arctic in Alaska (Barrow, Sagwon, Toolik) and Siberia (Tiksi), taken in the spring after thawing and in autumn prior to freezing. In addition to the long-term measurement fields, where sensors are installed deeper in the ground, we designed a monitoring setup for measuring moisture very close to the surface in the Lena River Delta, Siberia. The volumetric water content (VWC) and soil temperature sensors were placed in the moss organic layer in order to account for the limited penetration depth of the radar signal. ASCAT SSM variations are generally very small, in line with the low variability of in situ VWC. Short-term changes after complete thawing of the upper organic layer, however, seem to be mostly influenced by soil temperature. Correlations between SSM and in situ VWC are generally very low, or even negative. Mean standard deviation matching results in a comparably high root-mean-square error (on average 11%) for predictions of VWC. Further investigations and measurement networks are needed to clarify factors causing temporal variation of C band backscatter in tundra regions.

Transmittance fluctuations in turbulent atmospheric channels result in quadrature excess noise which limits applicability of continuous-variable quantum communication. Such fluctuations are commonly caused by beam wandering around the receiving aperture. We study the possibility to stabilize the fluctuations by expanding the beam, and test this channel stabilization in regard of continuous-variable entanglement sharing and quantum key distribution. We perform transmittance measurements of a real free-space atmospheric channel for different beam widths and show that the beam expansion reduces the fluctuations of the channel transmittance by the cost of an increased overall loss. We also theoretically study the possibility to share an entangled state or to establish secure quantum key distribution over the turbulent atmospheric channels with varying beam widths. We show the positive effect of channel stabilization by beam expansion on continuous-variable quantum communication as well as the necessity to optimize the method in order to maximize the secret key rate or the amount of shared entanglement. Being autonomous and not requiring adaptive control of the source and detectors based on characterization of beam wandering, the method of beam expansion can be also combined with other methods aiming at stabilizing the fluctuating free-space atmospheric channels.

The intellectual disability gene, Sox11, encodes for a critical neurodevelopmental transcription factor with functions in precursor survival, neuronal fate determination, migration and morphogenesis. The mechanisms regulating SOX11's activity remain largely unknown. Mass spectrometric analysis uncovered that SOX11 can be post-translationally modified by phosphorylation. Here, we report that phosphorylatable serines surrounding the high-mobility group box modulate SOX11's transcriptional activity. Through Mass Spectrometry (MS), co-immunoprecipitation assays and in vitro phosphorylation assays followed by MS we verified that protein kinase A (PKA) interacts with SOX11 and phosphorylates it on S133. In vivo replacement of SoxC factors in developing adult-generated hippocampal neurons with SOX11 S133 phospho-mutants indicated that phosphorylation on S133 modulates dendrite development of adult-born dentate granule neurons, while reporter assays suggested that S133 phosphorylation fine-tunes the activation of select target genes. These data provide novel insight into the control of the critical neurodevelopmental regulator SOX11 and imply SOX11 as a mediator of PKA-regulated neuronal development.

Background: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease. These criteria aimed to codify/reproduce the expert clinical diagnostic process and to help standardize diagnosis in research and clinical settings. Their accuracy compared with expert clinical diagnosis has not been tested. The objectives of this study were to validate the International Parkinson and Movement Disorder Society diagnostic criteria against a gold standard of expert clinical diagnosis, and to compare concordance/accuracy of the International Parkinson and Movement Disorder Society criteria to 1988 United Kingdom Brain Bank criteria., Methods: From 8 centers, we recruited 626 parkinsonism patients (434 PD, 192 non-PD). An expert neurologist diagnosed each patient as having PD or non-PD, regardless of International Parkinson and Movement Disorder Society criteria (gold standard, clinical diagnosis). Then a second neurologist evaluated the presence/absence of each individual item from the International Parkinson and Movement Disorder Society criteria. The overall accuracy/concordance rate, sensitivity, and specificity of the International Parkinson and Movement Disorder Society criteria compared with the expert gold standard were calculated., Results: Of 434 patients diagnosed with PD, 94.5% met the International Parkinson and Movement Disorder Society criteria for probable PD (5.5% false-negative rate). Of 192 non-PD patients, 88.5% were identified as non-PD by the criteria (11.5% false-positive rate). The overall accuracy for probable PD was 92.6%. In addition, 59.3% of PD patients and only 1.6% of non-PD patients met the International Parkinson and Movement Disorder Society criteria for clinically established PD. In comparison, United Kingdom Brain Bank criteria had lower sensitivity (89.2%, P = 0.008), specificity (79.2%, P = 0.018), and overall accuracy (86.4%, P < 0.001). Diagnostic accuracy did not differ according to age or sex. Specificity improved as disease duration increased., Conclusions: The International Parkinson and Movement Disorder Society criteria demonstrated high sensitivity and specificity compared with the gold standard, expert diagnosis, with sensitivity and specificity both higher than United Kingdom Brain Bank criteria. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)

Background: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease (PD). Although recent validation studies suggest high accuracy, one unmet need is for highly specific criteria for clinical trials in early/de novo PD., Objectives: The objective of this study was to generate and test a PD diagnostic criteria termed "clinically established early PD.", Methods: We modified the Movement Disorder Society criteria to increase specificity for early PD by removing all disease duration components and changing red flags to absolute exclusions. We then estimated the sensitivity/specificity of clinically established early PD criteria in patients with disease duration <5 years, selected from a 626-patient validation study., Results: After documentation of parkinsonism, 18 individual exclusion criteria are assessed that preclude the diagnosis of "clinically established early PD." Among 212 PD and 152 non-PD patients, the estimated specificity was 95.4%, with 69.8% sensitivity., Conclusions: We describe high-specificity criteria for de novo PD, which are freely available for use in clinical trials. © 2018 International Parkinson and Movement Disorder Society., (© 2018 International Parkinson and Movement Disorder Society.)

Introduction: The hummingbird sign and the morning glory flower sign, reflecting midbrain pathology on MRI, have previously been shown to separate patients with progressive supranuclear palsy (PSP) from those with Parkinson's disease (PD) and multiple system atrophy (MSA). The aim of the present study was to determine the diagnostic accuracy and reproducibility of visual assessment of midbrain atrophy patterns in a large cohort of patients with neurodegenerative parkinsonism., Methods: Retrospective analysis of midbrain atrophy patterns on T1-weighted MRI in a large cohort of patients with neurodegenerative parkinsonism and healthy controls who underwent MR imaging during their diagnostic work-up., Results: 481 patients with neurodegenerative parkinsonism and 79 healthy controls were included in the present study. The presence of the hummingbird sign had a specificity of 99.5% and a positive predictive value of 96.1% for a diagnosis of PSP while sensitivity was suboptimal with 51.6%. Similarly, the presence of the morning glory flower sign yielded a specificity of 97.7% for a diagnosis of PSP, but sensitivity was only 36.8%. Sensitivity of both signs was 35.3% in early, clinically unclassifiable parkinsonism. Visual assessment of these midbrain alterations showed excellent inter-rater agreement., Conclusion: Midbrain atrophy patterns are useful in the differential diagnosis of neurodegenerative parkinsonism but both the hummingbird sign and more so the morning glory flower sign suffer from low sensitivity, especially in early disease stages., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We use panel U.S. tax data spanning 2008-2013 to study the impact of the Affordable Care Act (ACA) young adult provision on an important demographic outcome: childbearing. The impact is theoretically ambiguous: gaining insurance may increase access to contraceptive services while also reducing the out-of-pocket costs of childbirth. Because employer-reported U.S. Wage and Tax Statements (W-2 forms) record access to employer-provided benefits, we can examine the impact of the coverage expansion by focusing on young adults whose parents have access to benefits. We compare those who are slightly younger than the age threshold with those who are slightly older. Our results suggest that the ACA young adult provision led to a modest decrease in childbearing.

SOX11 is a key Transcription Factor (TF) in the regulation of embryonic and adult neurogenesis, whose mutation has recently been linked to an intellectual disability syndrome in humans. SOX11's transient activity during neurogenesis is critical to ensure the precise execution of the neurogenic program. Here, we report that SOX11 displays differential subcellular localizations during the course of neurogenesis. Western-Blot analysis of embryonic mouse brain lysates indicated that SOX11 is post-translationally modified by phosphorylation. Using Mass Spectrometry, we found 10 serine residues in the SOX11 protein that are putatively phosphorylated. Systematic analysis of phospho-mutant SOX11 resulted in the identification of the S30 residue, whose phosphorylation promotes nuclear over cytoplasmic localization of SOX11. Collectively, these findings uncover phosphorylation as a novel layer of regulation of the intellectual disability gene Sox11.

Objectives: The objective of this study was to investigate perceptual decision-making and reflection impulsivity in drug naïve patients with restless legs syndrome (RLS) and patients with dopaminergic therapy., Methods: A total of 35 RLS patients (20 who were drug naïve regarding dopaminergic medication and 15 patients treated with dopaminergic therapy without augmentation or impulse control disorders) were included in this study. We used the Beads task and the Pixel task which assess reflection impulsivity and perceptual decision-making, respectively. Results were compared to 20 healthy controls., Results: Both RLS patient groups gathered less evidence than healthy controls in the Beads task before making a decision ( P < 0.001), but patients with dopaminergic treatment gathered less information than drug naïve patients ( P = 0.026). Moreover, both patient groups made more choices against the evidence than healthy controls (both P < 0.01), but there was no difference between the two patient groups. In the Pixel task, we found an effect of task difficulty on reaction times with patients and controls responding faster with reduced task difficulty. There was neither an effect of group on reaction times nor an effect of group on error rates., Conclusions: Reflection impulsivity is common in RLS patients, regardless whether they are drug naïve or treated with dopaminergic therapy. Thus, RLS patients tend to gather less information compared to healthy controls which could have a negative effect on decision-making in daily life and should be investigated further.

Qualitative and quantitative structural magnetic resonance imaging offer objective measures of the underlying neurodegeneration in atypical parkinsonism. Regional changes in tissue volume, signal changes and increased deposition of iron as assessed with different structural MRI techniques are surrogate markers of underlying neurodegeneration and may reflect cell loss, microglial proliferation and astroglial activation. Structural MRI has been explored as a tool to enhance diagnostic accuracy in differentiating atypical parkinsonian disorders (APDs). Moreover, the longitudinal assessment of serial structural MRI-derived parameters offers the opportunity for robust inferences regarding the progression of APDs. This review summarizes recent research findings as (1) a diagnostic tool for APDs as well as (2) as a tool to assess longitudinal changes of serial MRI-derived parameters in the different APDs., (© 2018 Elsevier Inc. All rights reserved.)

Background: Motor symptoms in Huntington's disease (HD) are heterogeneous with dystonia being described as a symptom with a very high prevalence not only in juvenile cases., Objective: Treatment options for dystonia are limited. Cannabinoids have been described as a potential treatment for patients with dystonia of a different origin. Here, we present early onset HD patients with a marked improvement of motor symptoms mainly due to alleviation of dystonia due to treatment with cannabinoids. In addition we review the current literature concerning the use of cannabinoids in HD., Method: The Unified Huntington's Disease Rating Scale (UHDRS) motor score, including a chorea and dystonia subscore, was conducted before and after the start of cannabinoids in seven patients without any other changes in medication., Results: The UHDRS motor score and the dystonia subscore (±SD) improved from 70.9 (25.5) to 60.6 (26.9) with a mean change of 10.3 [95% CI 6.0-14.6] and from 12.3 (4.0) to 8.0 (3.6) with a mean change of 4.3 [95% CI 2.3-6.3], respectively (both p = 0.018)., Conclusion: Improvement of motor symptoms, mainly dystonia, led to several relevant improvements from a global clinical perspective such as improvement of care, gait and fine motor skills and weight gain. Moreover, we observed changes in behavior with less irritability and apathy, as well as less hypersalivation in some cases.

The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology and error rates in the clinical diagnosis can be high even at specialized centres. Despite several limitations, magnetic resonance imaging (MRI) has undoubtedly enhanced the diagnostic accuracy in the differential diagnosis of neurodegenerative parkinsonism over the last three decades. This review aims to summarize research findings regarding the value of the different MRI techniques, including advanced sequences at high- and ultra-high-field MRI and modern image analysis algorithms, in the diagnostic work-up of Parkinson's disease. This includes not only the exclusion of alternative diagnoses for Parkinson's disease such as symptomatic parkinsonism and atypical parkinsonism, but also the diagnosis of early, new onset, and even prodromal Parkinson's disease.

Objectives: To investigate decision making in patients with primary restless legs syndrome (RLS) with and without augmentation treated with dopaminergic medication., Methods: A total of 64 non-demented RLS patients treated with dopaminergic medication with and without augmentation were included in this study. We used an information sampling task to assess how much evidence participants gather before making a decision. Performance was compared to the results of 21 healthy controls., Results: All patients with and without augmentation gathered less information than healthy controls before making a decision (p<0.001), but there was no difference between the two patient groups (p = 1.0). Furthermore, both patient groups made more irrational decisions (e.g. decisions against the evidence they had at the time) than healthy controls (p≤0.002). In addition, RLS patients with augmentation made significantly more irrational decisions than RLS patients without augmentation (p = 0.037) and controls (p<0.001)., Conclusions: Our results show that RLS patients treated with dopaminergic drugs, regardless of having augmentation or not, jumped to conclusions and decided significantly more often against the evidence they had at the time of their decision. However, those with augmentation performed worse than all other groups and made more often irrational decisions, a phenomenon which is also common in patients with substance abuse or behavioural addictions. Thus, jumping to conclusions and deciding with a higher degree of uncertainty as well as irrational decision making is more common in RLS patients treated with dopaminergic medication particularly in those with augmentation.

Digital signatures guarantee the authorship of electronic communications. Currently used "classical" signature schemes rely on unproven computational assumptions for security, while quantum signatures rely only on the laws of quantum mechanics to sign a classical message. Previous quantum signature schemes have used unambiguous quantum measurements. Such measurements, however, sometimes give no result, reducing the efficiency of the protocol. Here, we instead use heterodyne detection, which always gives a result, although there is always some uncertainty. We experimentally demonstrate feasibility in a real environment by distributing signature states through a noisy 1.6 km free-space channel. Our results show that continuous-variable heterodyne detection improves the signature rate for this type of scheme and therefore represents an interesting direction in the search for practical quantum signature schemes. For transmission values ranging from 100% to 10%, but otherwise assuming an ideal implementation with no other imperfections, the signature length is shorter by a factor of 2 to 10. As compared with previous relevant experimental realizations, the signature length in this implementation is several orders of magnitude shorter.

Objectives: To assess the frequency of impulse control disorders (ICDs) in patients with restless legs syndrome (RLS) with and without augmentation under dopaminergic therapy in a case-control study. Augmentation and ICDs are both serious complications of dopaminergic treatment of RLS but little is known about possible associations between these drug-induced disorders., Methods: In total, 58 patients with idiopathic RLS diagnosed according to the International Restless Legs Syndrome Study Group criteria were recruited. Of these, 35 patients had augmentation. The frequency of ICD symptoms was assessed using semi-structural interviews., Results: Demographic variables did not differ between patients with RLS with and without augmentation but those with augmentation took higher dopaminergic medication than patients without augmentation. Twenty-three patients with RLS (39.7%) had ICD symptoms, with 12 patients (20.7%) having definitive ICDs. Patients with augmentation had an increased risk of expressing ICD symptoms (p = 0.007, odds ratio 5.64, 95% confidence interval 1.59-20.02)., Conclusions: Patients with RLS with augmentation have an almost 6-fold increased risk of exhibiting ICD symptoms. This implies that augmentation and ICDs are related and may share a common pathophysiology. Moreover, our results have clinical implications, suggesting that patients with RLS with augmentation should be screened for ICD symptoms., (© 2016 American Academy of Neurology.)

Background: Cerebral hemiatrophy syndromes can present with variable neurological symptoms. In childhood epilepsy, mental retardation and neuropsychiatric disorders are common while in adults movement disorders, such as highly asymmetric parkinsonism or hemidystonia as well as neuropsychiatric problems have been reported., Methods: Here, we present three adult patients with features that expand the clinical spectrum and give an overview of the most common clinical signs associated with this rare condition., Results: All three patients had prominent neuropsychiatric symptoms such as mood swings and increased irritability. Furthermore, one patient developed hemichorea which can be a rare presentation of cerebral hemiatrophy., Conclusions: Cerebral hemiatrophy syndromes are a heterogeneous group of disorders that may also present with neuropsychiatric symptoms or hemichorea.

A circumpolar representative and consistent wetland map is required for a range of applications ranging from upscaling of carbon fluxes and pools to climate modelling and wildlife habitat assessment. Currently available data sets lack sufficient accuracy and/or thematic detail in many regions of the Arctic. Synthetic aperture radar (SAR) data from satellites have already been shown to be suitable for wetland mapping. Envisat Advanced SAR (ASAR) provides global medium-resolution data which are examined with particular focus on spatial wetness patterns in this study. It was found that winter minimum backscatter values as well as their differences to summer minimum values reflect vegetation physiognomy units of certain wetness regimes. Low winter backscatter values are mostly found in areas vegetated by plant communities typically for wet regions in the tundra biome, due to low roughness and low volume scattering caused by the predominant vegetation. Summer to winter difference backscatter values, which in contrast to the winter values depend almost solely on soil moisture content, show expected higher values for wet regions. While the approach using difference values would seem more reasonable in order to delineate wetness patterns considering its direct link to soil moisture, it was found that a classification of winter minimum backscatter values is more applicable in tundra regions due to its better separability into wetness classes. Previous approaches for wetland detection have investigated the impact of liquid water in the soil on backscatter conditions. In this study the absence of liquid water is utilized. Owing to a lack of comparable regional to circumpolar data with respect to thematic detail, a potential wetland map cannot directly be validated; however, one might claim the validity of such a product by comparison with vegetation maps, which hold some information on the wetness status of certain classes. It was shown that the Envisat ASAR-derived classes are related to wetland classes of conventional vegetation maps, indicating its applicability; 30% of the land area north of the treeline was identified as wetland while conventional maps recorded 1-7%.

By performing quantum-noise-limited optical heterodyne detection, we observe polarization noise in light after propagation through a hollow-core photonic crystal fiber (PCF). We compare the noise spectrum to the one of a standard fiber and find an increase of noise even though the light is mainly transmitted in air in a hollow-core PCF. Combined with our simulation of the acoustic vibrational modes in the hollow-core PCF, we are offering an explanation for the polarization noise with a variation of guided acoustic wave Brillouin scattering (GAWBS). Here, instead of modulating the strain in the fiber core as in a solid core fiber, the acoustic vibrations in hollow-core PCF influence the effective refractive index by modulating the geometry of the photonic crystal structure. This induces polarization noise in the light guided by the photonic crystal structure.

Quantum annealers use quantum fluctuations to escape local minima and find low-energy configurations of a physical system. Strong evidence for superiority of quantum annealing (QA) has come from comparing QA implemented through quantum Monte Carlo (QMC) simulations to classical annealing. Motivated by recent experiments, we revisit the question of when quantum speedup may be expected. Although a better scaling is seen for QA in two-dimensional Ising spin glasses, this advantage is due to time discretization artifacts and measurements that are not possible on a physical quantum annealer. Simulations in the physically relevant continuous time limit, on the other hand, do not show superiority. Our results imply that care must be taken when using QMC simulations to assess the potential for quantum speedup., (Copyright © 2015, American Association for the Advancement of Science.)

Continuous variable quantum states of light are used in quantum information protocols and quantum metrology and known to degrade with loss and added noise. We were able to show the distribution of bright polarization squeezed quantum states of light through an urban free-space channel of 1.6 km length. To measure the squeezed states in this extreme environment, we utilize polarization encoding and a postselection protocol that is taking into account classical side information stemming from the distribution of transmission values. The successful distribution of continuous variable squeezed states is accentuated by a quantum state tomography, allowing for determining the purity of the state.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common genetic cause of Parkinson's disease (PD). However, LRRK2 function and molecular mechanisms causing the parkinsonian phenotype remain widely unknown. Most of LRRK2 knockdown and overexpression models strengthen the relevance of LRRK2 in regulating neurite outgrowth. We have recently identified ARHGEF7 as the first guanine nucleotide exchange factor (GEF) of LRRK2. This GEF is influencing neurite outgrowth through regulation of actin polymerization. Here, we examined the expression profile of neuroblastoma cells with reduced LRRK2 and ARHGEF7 levels to identify additional partners of LRRK2 in this process. Tropomyosins (TPMs), and in particular TPM4, were the most interesting candidates next to other actin cytoskeleton regulating transcripts in this dataset. Subsequently, enhanced neurite branching was shown using primary hippocampal neurons of LRRK2 knockdown animals. Furthermore, we observed an enhanced number of growth cones per neuron and a mislocalization and dysregulation of ARHGEF7 and TPM4 in these neuronal compartments. Our results reveal a fascinating connection between the neurite outgrowth phenotype of LRRK2 models and the regulation of actin polymerization directing further investigations of LRRK2-related pathogenesis., (© 2013.)

Transdermal delivery of anti-inflammatory medications, both nonsteroidal and corticosteroids, has enjoyed at least a decade of success in Canada and the US. Iontophoresis and phonophoresis offer substantial benefits for the transdermal delivery of these medications and can be valuable additions to existing treatment modalities for minor sports-related injuries. Included with this article is historical and explanatory information about iontophoresis and phonophoresis, as well as formulations and case reports related to the treatment of sports-related injuries. The article emphasizes the importance of a compounding pharmacist's involvement in developing a successful treatment plan.

Purpose: Evaluation of technical success and follow-up of patients with osteoid osteoma., Material and Methods: 9 patients (3 w, 6 m) with a mean age of 22.3 years suffering from an osteoid osteoma localized in the femur were treated with a combination therapy based on drill trepanation of the nidus and subsequent installation of 1-2 ml ethanol (96%). The treatment was done under CT-guidance in general anaesthesia., Results: During the follow-up period of 20.6 months (10 to 39 months) one relapse occurred within 3 months. This was treated with the same percutaneous method., Conclusions: Percutaneous removal of intracortical osteoid osteomas under CT-guidance had success in this study, was technical easy, and a had low relapse rate. In addition the duration of hospitalisation is shorten. Meanwhile other studies have used additive ablation with radiofrequency. A second study has been started in our department using a thermoablative procedure. In a comparison between surgical and radiological methods, the rates of relapse are similar (9% vs. 23% surgically). The CT-guided removal of intracortical osteoid osteomas should be the procedure of first choice.

Villoglandular adenocarcinoma of the cervix is a distinct histologic type of cervical cancer. Fewer than 60 cases have been reported in the literature. Previous reports suggest that, due to the highly favorable prognosis of this rare histologic type of cervical cancer, conservative surgical therapy with cervical conization or extrafascial hysterectomy alone may be undertaken. In this series, three cases of villoglandular adenocarcinoma of the cervix are described. Preoperatively in each case, the cancer was confined to the cervix and histologic well-differentiated villoglandular adenocarcinoma of the cervix was confirmed. Extended hysterectomy was performed in all cases. In one case, residual invasive endocervical adenocarcinoma was noted. Careful review of the histologic characteristics of these tumors is needed when deciding if these patients can be managed with conservative therapy.

Four hundred sixty-nine serum samples were obtained from horses admitted to the internal medicine service of the Texas Veterinary Medical Center between Jan 1 and Dec 31, 1990. Serum samples were tested by ELISA for antibody to Borrelia burgdorferi. Of these 469 samples, 1 (0.2%) was repeatedly seropositive for the organism by ELISA. Confirmatory testing by protein immunoblot was negative. The observed seroprevalence was 0%; the upper bound of the 95% confidence interval was 0.6%. These findings indicate the evidence of infection with B burgdorferi is presently uncommon in horses in central Texas.

Fluence rate-response curves were determined for the inhibition of hypocotyl growth in 54 h old dark-grownSinapis alba L. seedlings by continuous or hourly 5 min red light irradiation (24 h). In both cases a fluence rate-dependence was observed. More than 90% of the continuous light effect could be substituted for by hourly light pulses if the total fluence of the two different light regimes was the same. Measurements of the far red absorbing form of phytochrome ([P fr]) and [P fr]/[P tot] (total phytochrome) showed a strong fluence rate-dependence under continuous and pulsed light which partially paralleled the fluence rate-response curves for the inhibition of the hypocotyl growth.