Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials.

BACKGROUND: Parkinson\u27s disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life. OBJECTIVE: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes. METHODS: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12. RESULTS: Diaries were evaluable for 162 patients. At baseline, 67% of patients woke up OFF, with prevalence decreasing to 13% at 2 hours and then remaining relatively steady at ∼12% (range, 6-17%) across half-hour intervals thereafter. Troublesome dyskinesia prevalence rose steadily from 5% to 24% over the first 2 hours, then fluctuated between 20% and 44% through the rest of the waking day. At baseline, patients experienced a mean of 3.0 daily episodes of troublesome dyskinesia (average duration 2.0 hours each), and 2.2 daily episodes of OFF (average duration 1.1 hour each). At week 12, Gocovri-treated patients showed greater reductions than placebo in troublesome dyskinesia and OFF episodes per day (treatment difference: -1.0 episodes and -0.4 episodes, respectively) and average episode duration (treatment difference: -0.6 hours and -0.3 hours, respectively). Mean duration of individual episodes of ON without troublesome dyskinesia (Good ON) increased by 5.0 hours for Gocovri, compared with 2.0 hours for placebo. Patients taking Gocovri experienced 2.2 fewer transitions between states than patients taking placebo. CONCLUSIONS: Troublesome dyskinesia and OFF occurred in the morning and throughout the waking day. Gocovri-treated patients experienced fewer, shorter episodes of both troublesome dyskinesia and OFF, thereby increasing the duration of continuous Good ON episodes and reducing the frequency of transitions between motor states

'Alive after five' : constructing the neoliberal night in Newcastle upon Tyne.

The development of the ‘night-time economy’ in the UK through the 1990s has been associated with neoliberal urban governance. Academics have, however, begun to question the use and the scope of the concept ‘neoliberalism’. In this paper, I identify two common approaches to studying neoliberalism, one exploring neoliberalism as a series of policy networks, the other exploring neoliberalism as the governance of subjectivities. I argue that to understand the urban night, we need to explore both these senses of ‘neoliberalism’. As a case study, I take the ‘Alive After Five’ project, organised by the Business Improvement District in Newcastle-upon-Tyne, which sought to extend shopping hours in order to encourage more people to use the city at night. Drawing from Actor-Network-Theory, I explore the planning, the translation, and the practice of this new project. In doing so, I explore the on-going nature and influence of neoliberal policy on the urban night in the UK

Efficacy results of pimavanserin from a multi-center, open-label extension study in Parkinson's disease psychosis patients

© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.Introduction: Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved for hallucinations and delusions associated with Parkinson's disease psychosis (PDP). We present durability of response with pimavanserin in patients with PDP for an additional 4 weeks of treatment. Methods: This was an open-label extension (OLE) study in patients previously completing one of three double-blind, placebo-controlled (Core) studies. All patients received pimavanserin 34 mg once daily. Efficacy assessments included the Scale for the Assessment of Positive Symptoms (SAPS) PD and H + D scales, Clinical Global Impression (CGI) Improvement and Severity scales and Caregiver Burden Scale (CBS), through 4 weeks in the OLE. Safety assessments were conducted at each visit. Results: Of 459 patients, 424 (92.4%) had a Week 4 efficacy assessment. At Week 4 (10 weeks total treatment), SAPS-PD mean (standard deviation) change from OLE baseline was -1.8 (5.5) and for SAPS-H + D was -2.1 (6.2) with pimavanserin 34 mg. Patients receiving placebo during the Core studies had greater improvements (SAPS-PD -2.9 [5.6]; SAPS-H + D -3.5 [6.3]) during the OLE. For participants treated with pimavanserin 8.5 or 17 mg during the Core studies, further improvement was observed during the OLE with pimavanserin 34 mg. The mean change from Core Study baseline for SAPS-PD score was similar among prior pimavanserin 34 mg and prior placebo-treated participants (-7.1 vs. -7.0). The CGI-I response rate (score of 1 or 2) at Week 4 was 51.4%. Adverse events were reported by 215 (46.8%) patients during the first 4 weeks of OLE. The most common AEs were fall (5.9%), hallucination (3.7%), urinary tract infection (2.8%), insomnia (2.4%), and peripheral edema (2.2%) CONCLUSIONS: Patients previously on pimavanserin 34 mg during three blinded core studies had durability of efficacy during the subsequent 4 week OLE SAPS-PD assessment. Patients previously on blinded placebo improved after 4 weeks of OL pimavanserin treatment. These results in over 400 patients from 14 countries support the efficacy of pimavanserin for treating PDP.info:eu-repo/semantics/publishedVersio

Muonium as a hydrogen analogue in silicon and germanium; quantum effects and hyperfine parameters

We report a first-principles theoretical study of hyperfine interactions, zero-point effects and defect energetics of muonium and hydrogen impurities in silicon and germanium. The spin-polarized density functional method is used, with the crystalline orbitals expanded in all-electron Gaussian basis sets. The behaviour of hydrogen and muonium impurities at both the tetrahedral and bond-centred sites is investigated within a supercell approximation. To describe the zero-point motion of the impurities, a double adiabatic approximation is employed in which the electron, muon/proton and host lattice degrees of freedom are decoupled. Within this approximation the relaxation of the atoms of the host lattice may differ for the muon and proton, although in practice the difference is found to be slight. With the inclusion of zero-point motion the tetrahedral site is energetically preferred over the bond-centred site in both silicon and germanium. The hyperfine and superhyperfine parameters, calculated as averages over the motion of the muon, agree reasonably well with the available data from muon spin resonance experiments.Comment: 20 pages, including 9 figures. To appear in Phys. Rev.

Muon spin relaxation study of spin dynamics in poly(triarylamine)

Organic semiconductors (OSCs) have been of great interest over the last couple of decades owing to their mechanic flexibility, ease of processing, high tuneability and availability. One area of OSCs that is of growing interest is polymers as they possess many of the desirable properties, in particular print processing and tunability of electronic properties, necessary for application in devices such as organic solar cells and the spin valves being engineered for hard disks and logic devices. Much focus has been given in recent years to the areas of research including the electron and hole dynamics, transport mechanisms and spin relaxation in OSCs in order to utilise them in novel organic devices. In this paper the µSR technique is applied to carry out an in depth study of the electron dynamics and spin relaxation in the commonly used Poly(triarylamine) polymer (PTAA). It is shown that the electron wavefunction can be considered localised to the aromatic rings providing a strong hyperfine coupling interaction with the muon. In addition the presence of an electron spin relaxation (eSR) is demonstratated that resembles that previously reported in the small organic molecule series

Temporal mapping of photochemical reactions and molecular excited states with carbon specificity

Photochemical reactions are essential to a large number of important industrial and biological processes. A method for monitoring photochemical reaction kinetics and the dynamics of molecular excitations with spatial resolution within the active molecule would allow a rigorous exploration of the pathway and mechanism of photophysical and photochemical processes. Here we demonstrate that laser-excited muon pump-probe spin spectroscopy (photo-μSR) can temporally and spatially map these processes with a spatial resolution at the single-carbon level in a molecule with a pentacene backbone. The observed time-dependent light-induced changes of an avoided level crossing resonance demonstrate that the photochemical reactivity of a specific carbon atom is modified as a result of the presence of the excited state wavefunction. This demonstrates the sensitivity and potential of this technique in probing molecular excitations and photochemistry

The rhythms of life: what your body clock means to you!

Until we turned our nights into days and began to travel in aircraft across multiple time zones, we were largely unaware that we possess a 'day within' driven by an internal body clock. Yet the striking impairment of our abilities in the early hours of the morning soon reminds us that we are slaves to our biology. Our ability to perform mathematical calculations or other intellectual tasks between 04.00 and 06.00 h is worse than if we had consumed several shots of whisky and would be classified as legally drunk. Biological clocks drive or alter our sleep patterns, alertness, mood, physical strength, blood pressure and every other aspect of our physiology and behaviour. Our emerging understanding of how these 24 h rhythms are generated and regulated is not only one of the great success stories of modern biology, but is also informing many areas of human health. Sleep and circadian rhythm disruption (SCRD) is a feature shared by some of the most challenging diseases of our time, including neuropsychiatric illness and serious disorders of the eye. Sleep and circadian rhythm disruption is also commonly seen across many sectors of society, from teenagers to shift workers. We also now appreciate that SCRD is far more than feeling sleepy at an inappropriate time. It promotes multiple illnesses ranging across abnormal metabolism, heart disease, reduced immunity, increased stress and abnormal cognition and mood states. This short review considers how 24 h rhythms are generated and regulated, the consequences of working against our body clock and the emerging relationship between SCRD and mental illness

Seasons of life: The biological rhythms that enable living things to thrive and survive

Just as daily events are timed by living creatures through circadian rhythms, so seasonal events are timed through an internal calendar that signals birds to return to nesting grounds, salmon to spawn, plants to flower, squirrels to hibernate, kelp to stop growing. In this fascinating book, Russell G. Foster and Leon Kreitzman draw on remarkable recent scientific advances to explain how seasonal change affects organisms, and how plants and animals over countless generations have evolved exquisite sensitivities and adaptations to the seasons. The authors also highlight the impact of seasonal change on human health and well-being. They conclude with a discussion of the dangers posed when climate changes disrupt the seasonal rhythms on which so much life depends. © 2009 by Russell G. Foster and Leon Kreitzman

Seasons of life: The biological rhythms that enable living things to thrive and survive

Just as daily events are timed by living creatures through circadian rhythms, so seasonal events are timed through an internal calendar that signals birds to return to nesting grounds, salmon to spawn, plants to flower, squirrels to hibernate, kelp to stop growing. In this fascinating book, Russell G. Foster and Leon Kreitzman draw on remarkable recent scientific advances to explain how seasonal change affects organisms, and how plants and animals over countless generations have evolved exquisite sensitivities and adaptations to the seasons. The authors also highlight the impact of seasonal change on human health and well-being. They conclude with a discussion of the dangers posed when climate changes disrupt the seasonal rhythms on which so much life depends. © 2009 by Russell G. Foster and Leon Kreitzman

Licenced to drive at 85? A report on the mobility needs of older people in the next 25 years

SIGLEAvailable from British Library Document Supply Centre-DSC:m01/35824 / BLDSC - British Library Document Supply CentreGBUnited Kingdo