Treatment with istradefylline for postural abnormalities in Parkinson’s disease

Introduction. In the current edition, Fujioka and colleagues report on four Japanese patients with Parkinson disease (PD) and severe postural abnormalities treated with istradefylline (adenosine A2A receptor antagonist); further, dopamine agonists were with- drawn. Three patients experienced significant improvements of postural abnormalities. Clinical reflections. Postural abnormalities in PD include camptocormia, antecollis, lateral trunk flexion, and scoliosis. They may be very pronounced and significantly reduce quality of life. The therapy of postural deformities in PD is currently disappointing. Clinical implications. Effective therapeutic strategies for postural deformities in PD are an unmet need. Larger clinical trials investigating novel approaches including istradefylline are warranted

Specific heat in two-dimensional melting

We report the specific heat $c_N$ around the melting transition(s) of micrometer-sized superparamagnetic particles confined in two dimensions, calculated from fluctuations of positions and internal energy, and corresponding Monte Carlo simulations. Since colloidal systems provide single particle resolution, they offer the unique possibility to compare the experimental temperatures of peak position of $c_N(T)$ and symmetry breaking, respectively. While order parameter correlation functions confirm the Kosterlitz-Thouless-Halperin-Nelson-Young melting scenario where translational and orientational order symmetries are broken at different temperatures with an intermediate so called hexatic phase, we observe a single peak of the specific heat within the hexatic phase, with excellent agreement between experiment and simulation. Thus, the peak is not associated with broken symmetries but can be explained with the total defect density, which correlates with the maximum increase of isolated dislocations. The absence of a latent heat strongly supports the continuous character of both transitions

Two-dimensional melting under quenched disorder

We study the influence of quenched disorder on the two-dimensional melting behavior by using both video-microscopy of superparamagnetic colloidal particles and computer simulations of repulsive parallel dipoles. Quenched disorder is provided by pinning a fraction of the particles. We confirm the occurrence of the Kosterlitz-Thouless-Halperin-Nelson-Young scenario with an intermediate hexatic phase. While the fluid-hexatic transition remains largely unaffected by disorder, the hexatic-solid transition shifts towards lower temperatures for increasing disorder resulting in a significantly broadened stability range of the hexatic phase. In addition, we observe spatio-temporal critical(-like) fluctuations consistent with the continuous character of the phase transitions.Comment: 5 pages, 4 figure

Free will beliefs are better predicted by dualism than determinism beliefs across different cultures

Most people believe in free will. Whether this belief is warranted or not, free will beliefs (FWB) are foundational for many legal systems and reducing FWB has effects on behavior from the motor to the social level. This raises the important question as to which specific FWB people hold. There are many different ways to conceptualize free will, and some might see physical determinism as a threat that might reduce FWB, while others might not. Here, we investigate lay FWB in a large, representative, replicated online survey study in the US and Singapore (n = 1800), assessing differences in FWB with unprecedented depth within and between cultures. Specifically, we assess the relation of FWB, as measured using the Free Will Inventory, to determinism, dualism and related concepts like libertarianism and compatibilism. We find that libertarian, compatibilist, and dualist, intuitions were related to FWB, but that these intuitions were often logically inconsistent. Importantly, direct comparisons suggest that dualism was more predictive of FWB than other intuitions. Thus, believing in free will goes hand-in-hand with a belief in a non-physical mind. Highlighting the importance of dualism for FWB impacts academic debates on free will, which currently largely focus on its relation to determinism. Our findings also shed light on how recent (neuro)scientific findings might impact FWB. Demonstrating physical determinism in the brain need not have a strong impact on FWB, due to a wide-spread belief in dualism

Formation of helical ion chains

We study the nonequilibrium dynamics of the linear to zigzag structural phase transition exhibited by an ion chain confined in a trap with periodic boundary conditions. The transition is driven by reducing the transverse confinement at a finite quench rate, which can be accurately controlled. This results in the formation of zigzag domains oriented along different transverse planes. The twists between different domains can be stabilized by the topology of the trap and under laser cooling the system has a chance to relax to a helical chain with nonzero winding number. Molecular dynamics simulations are used to obtain a large sample of possible trajectories for different quench rates. The scaling of the average winding number with different quench rates is compared to the prediction of the Kibble-Zurek theory, and a good quantitative agreement is found

Multisensory interactions in Virtual Reality: optic flow reduces vestibular sensitivity, but only for congruent planes of motion

During exposure to Virtual Reality (VR) a sensory conflict may be present, whereby the visual system signals that the user is moving in a certain direction with a certain acceleration, while the vestibular system signals that the user is stationary. In order to reduce this conflict, the brain may down-weight vestibular signals, which may in turn affect vestibular contributions to self-motion perception. Here we investigated whether vestibular perceptual sensitivity is affected by VR exposure. Participants’ ability to detect artificial vestibular inputs was measured during optic flow or random motion stimuli on a VR head-mounted display. Sensitivity to vestibular signals was significantly reduced when optic flow stimuli were presented, but importantly this was only the case when both visual and vestibular cues conveyed information on the same plane of self-motion. Our results suggest that the brain dynamically adjusts the weight given to incoming sensory cues for self-motion in VR; however this is dependent on the congruency of visual and vestibular cues

Responsibility without freedom? Folk judgements about deliberate actions

A long-standing position in philosophy, law, and theology is that a person can be held morally responsible for an action only if they had the freedom to choose and to act otherwise. Thus, many philosophers consider freedom to be a necessary condition for moral responsibility. However, empirical findings suggest that this assumption might not be in line with common sense thinking. For example, in a recent study we used surveys to show that – counter to positions held by many philosophers – lay people consider actions to be free when they are spontaneous rather than being based on reasons. In contrast, responsibility is often considered to require that someone has thought about the alternative options. In this study we used an online survey to directly test the degree to which lay judgements of freedom and responsibility match. Specifically, we tested whether manipulations of deliberation affect freedom and responsibility judgements in the same way. Furthermore, we also tested the dependency of these judgements on a person’s belief that their decision had consequences for their personal life. We found that deliberation had an opposite effect on freedom and responsibility judgements. People were considered more free when they acted spontaneously, whereas they were considered more responsible when they deliberated about their actions. These results seem to suggest that deliberating about reasons is crucially important for the lay concept of responsibility, while for the lay notion of freedom it is perceived to be detrimental. One way of interpreting our findings for the interdisciplinary debate on free will and responsibility could be to suggest that lay beliefs match the philosophical position of semi-compatibilism. Semi-compatibilists insist that the metaphysical debate on the nature of free will can be separated from the debate on conditions of responsible agency. According to our findings the beliefs of lay people are in line with views held by semi-compatibilists, even though we did not test whether they endorse that position explicitly

Multisensory Integration in Self Motion Perception

Self motion perception involves the integration of visual, vestibular, somatosensory and motor signals. This article reviews the findings from single unit electrophysiology, functional and structural magnetic resonance imaging and psychophysics to present an update on how the human and non-human primate brain integrates multisensory information to estimate one's position and motion in space. The results indicate that there is a network of regions in the non-human primate and human brain that processes self motion cues from the different sense modalities

Genome-wide association and Meta-analysis of age at onset in Parkinson Disease

Background and Objectives Considerable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations. Methods A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC). Results The COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10−8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), pCOURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), pCOURAGE+IPDGC = 3.13 × 10−9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = −0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10−8). Discussion Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD

Antioxidant plants and diabetes mellitus

The incidence of diabetes mellitus (DM) is increasing rapidly and it is expected to increase by 2030. Other than currently available therapeutic options, there are a lot of herbal medicines, which have been recommended for its treatment. Herbal medicines have long been used for the treatment of DM because of the advantage usually having no or less side-effects. Most of these plants have antioxidant activities and hence, prevent or treat hard curable diseases, other than having the property of combating the toxicity of toxic or other drugs. In this review other than presenting new findings of DM, the plants, which are used and have been evaluated scientifically for the treatment of DM are introduced