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Colin Tuft,1 Elie Matar,2 Zoe Menczel Schrire,2 Ronald R Grunstein,2,3 Brendon J Yee,1– 3 Camilla M Hoyos2,4 1Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney Medical School, Sydney, NSW, Australia; 3Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; 4School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, AustraliaCorrespondence: Camilla M Hoyos, Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research, Sydney Medical School, Sydney, NSW, Australia, Tel +61 2 9114 0409, Email camilla.hoyos@sydney.edu.auAbstract: Exogenous melatonin is commonly used for sleep disorders in older adults, and its use is increasing over time. It appears to have modest efficacy in treating insomnia and circadian rhythm sleep-wake disorders. Melatonin is commonly perceived to be a safe alternative to other hypnotics and is available without prescription in some jurisdictions. New evidence suggests that endogenous melatonin has pleomorphic effects on multiple organ systems, many of which are poorly understood. This narrative review summarizes the current evidence regarding the safety of melatonin in older adults (defined by age over 65 years). Melatonin appears to have a favorable safety profile in this population, however there is a dearth of evidence regarding the safety of prolonged use. There are several factors which increase the risk of adverse effects of melatonin in older adults, and these should be taken into consideration when prescribing to this population.Keywords: adverse effect, safety, insomnia, elderly, sleep wake phase disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically occurs in the context of synuclein-based neurodegenerative disorders but can also be seen accompanying brain lesions and be exacerbated by medications, particularly antidepressants. There is also an increasing appreciation regarding isolated or idiopathic RBD (iRBD). Symptomatic treatment of RBD is a priority to prevent injurious complications, with usual choices being melatonin or clonazepam. The discovery that iRBD represents a prodromal stage of incurable synucleinopathies has galvanized the research community into delineating the pathophysiology of RBD and defining biomarkers of neurodegeneration that will facilitate future disease-modifying trials in iRBD. Despite many advances, there has been no progress in available symptomatic or neuroprotective therapies for RBD, with recent negative trials highlighting several challenges that need to be addressed to prepare for definitive therapeutic trials for patients with this disorder. These challenges relate to i) the diagnostic and screening strategies applied to RBD, ii) the limited evidence base for symptomatic therapies, (iii) the existence of possible subtypes of RBD, (iv) the relevance of triggering medications, (v) the absence of objective markers of severity, (vi) the optimal design of disease-modifying trials, and vii) the implications around disclosing the risk of future neurodegeneration in otherwise healthy individuals. Here, we review the current concepts in the therapeutics of RBD as it relates to the above challenges and identify pertinent research questions to be addressed by future work. [ABSTRACT FROM AUTHOR]

Using the King and Wells method, we present experimental data on the dependence of the sticking of molecular hydrogen and deuterium on the beam temperature onto nonporous amorphous solid water ice surfaces of interstellar interest. A statistical model that explains the isotopic effect and the beam temperature behavior of our data is proposed. This model gives an understanding of the discrepancy between all known experimental results on the sticking of molecular hydrogen. Moreover, it is able to fit the theoretical results of Buch et al. [Astrophys. J. 379, 647 (1991)] on atomic hydrogen and deuterium. For astrophysical applications, an analytical formula for the sticking coefficients of H, D, H2, D2, and HD in the case of a gas phase at thermal equilibrium is also provided at the end of the article. [ABSTRACT FROM AUTHOR]

Freezing of gait (FOG) is a disabling form of gait disturbance that is common in the advanced stages of Parkinson's disease (PD). Despite its prevalence, methods of studying and assessing FOG are limited. We have previously shown that a virtual reality paradigm was able to distinguish between those who report FOG ("freezers") and those who do not report FOG ("non-freezers"). In this paradigm, 'freezers' were found to have prolonged footstep latency in response to known triggers of FOG including doorways, sliding doors and dual-tasking. In this study, we employed the same paradigm to assess performance of 27 freezers and 14 non-freezers in their clinical 'on' and 'off' medication states. In this study, only participants in the freezing group demonstrated statistically significant increases in latencies experienced in the 'off' state compared to the 'on' state in response to wide and narrow doorways and the opening of a sliding door. By contrast, these behavioral differences were not apparent in non-freezers. Furthermore the delay was specific to environmental cues and was not due to generalized slowing in the 'off' state. The findings suggest that this motor delay when processing environmentally salient cues is specific to freezers and is partially mediated by dopamine-dependent neurocircuitry. [ABSTRACT FROM AUTHOR]

Abstract: Freezing of gait is a paroxysmal and disabling symptom that commonly affects patients in the latter stages of Parkinson''s disease, however the intermittent nature of this symptom makes it difficult to study in the clinical setting. Our research group has previously reported a correlation between self-reported freezing of gait symptoms and performance on a seated virtual reality gait task. In this study, we sought to determine whether behavioral measures recorded on this task were correlated with actual clinical measures of freezing of gait recorded in a cohort of 38 Parkinson''s disease patients whilst in their clinically defined ‘off’ state. Firstly, patients with freezing of gait had a significantly larger frequency of spontaneous motor arrests recorded on the virtual reality gait task than ‘non-freezers’. In addition, in those 24 patients with clinically proven freezing of gait, the number and percentage of time spent with freezing on the virtual reality task were both moderately correlated with the duration of freezing of gait recorded on the timed up-and-go tasks. These findings suggest that the freezing behavior observed during a virtual reality gait task may share similar neural substrates to freezing of gait. Such a relationship could offer a potential avenue for modeling the phenomenon of freezing of gait in Parkinson''s disease, allowing for the exploration of the neural correlates of freezing. [Copyright &y& Elsevier]

Interstellar water ice is mainly amorphous, but the nature of its morphology still remains poorly known. The experimental study described in this work focuses on how relevant changes of the ice morphology result from atomic hydrogen exposure and subsequent recombination. We show that there is an exponential decrease in the porosity of the amorphous water ice sample following hydrogen-atom irradiation. These and other laboratory results lead us to suggest that water ice in space is almost certainly amorphous and non-porous (compact). [ABSTRACT FROM AUTHOR]

Context. Sticking of H and D atoms on interstellar dust grains is the first step in molecular hydrogen formation, which is a key reaction in the interstellar medium. Isotopic properties of the sticking can have an incidence on the observed HD molecule. Aims. After studying the sticking coefficients of H2 and D2 molecules on amorphous silicate surfaces experimentally and theoretically, we extrapolate the results to the sticking coefficient of atoms and propose a formulae that gives the sticking coefficients of H and D on both silicates and icy dust grains. Methods. In our experiments, we used the King and Wells method for measuring the sticking coefficients of H2 and D2 molecules on a silicate surface held at 10 K. It consists of measuring with a QMS (quadrupole mass spectrometer) the signals of H2 and D2 molecules reflected by the surface during the exposure of the sample to the molecular beam at a temperature ranging from 20 K to 340 K. We tested the efficiency of a physical model, developed previously for sticking on water-ice surfaces. We applied this model to our experimental results for the sticking coefficients of H2 and D2 molecules on a silicate surface and estimated the sticking coefficient of atoms by a single measurement of atomic recombination and propose an extrapolation. Results. Sticking of H, D, HD, H2, and D2 on silicates grains behaves the same as on icy dust grains. The sticking decreases with the gas temperature, and is dependent on the mass of the impactor. The sticking coefficient for both surfaces and impactors can be modeled by an analytical formulae S (T) = S0(1 + βT/T0)/(1 + T/T0)β, which describes both the experiments and the thermal distribution expected in an astrophysical context. The parameters S0 and T0 are summarized in a table. Conclusions. Previous estimates for the sticking coefficient of H atoms are close to the new estimation; however, we find that, when isotopic effects are taken into account, the sticking coefficient variations can be as much as a factor of 2 at T = 100 K. [ABSTRACT FROM AUTHOR]

Nuclear spin conversion (NSC) of ortho- to para-H2and para- to ortho-D2has been investigated on an amorphous solid water (ASW) surface at 10 K, in the presence of co-adsorbed O2. The dynamics of the nuclear spin conversion could be revealed by combination of resonance enhanced multiphoton ionization spectroscopy (REMPI) with temperature programmed desorption (TPD) experiments. The conversion rates are consistent with a diffusion of molecular hydrogen inducing a nuclear spin conversion enhanced in the vicinity of molecular oxygen. The conversion times were found to increase with decreasing O2and H2coverage. Finally, on oxygen free ASW surface, the extremely long conversion characteristic times measured showed that such surface is not an efficient catalyst for NSC, in contradiction with hypothesis commonly made for interstellar medium. [ABSTRACT FROM AUTHOR]

Objective: To report a case with early presentation of acute lymphoblastic leukemia (ALL) as bilateral renal masses and renal failure. Clinical Presentation and Intervention: A 6-year-old boy was admitted with bilaterally enlarged kidneys and severe renal impairment. Magnetic resonance imaging (MRI) showed bilateral renal enlargement with features suggestive of an infiltrative lesion. Accordingly, bone marrow examination was performed, and diagnosis of ALL was made. The patient developed acute renal failure after initiation of chemotherapy, so he received hemodialysis. His renal function normalized and kidney enlargement regressed. Conclusion: This case demonstrates an unusual early renal involvement in ALL in a child. MRI is a valuable imaging modality in the evaluation of renal masses. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

There has always been a great deal of interest in the formation of H2 as well as in the binding energy released upon its formation on the surface of dust grains. The present work aims at collecting experimental evidence for how the bond energy budget of H2 is distributed between the reaction site and the internal energy of the molecule. So far, the non-detection of excited nascent H2 in dense quiescent clouds could be a sign that either predictions of emission line intensities are not correct or the de-excitation of the newly formed molecules proceeds rapidly on the grain surface itself. In this Letter, we present experimental evidence that interstellar molecular hydrogen is formed and then rapidly de-excited on the surface of porous water ice mantles. In addition, although we detect ro-vibrationally excited nascent molecules desorbing from a bare non-porous (compact) water ice film, we demonstrate that the amount of excited nascent hydrogen molecules is significantly reduced no matter the morphology of the water ice substrate at 10 K (both on non-porous and on porous water ice) in a regime of high molecular coverage as is the case in dark molecular clouds. [ABSTRACT FROM AUTHOR]

This paper provides a new algorithm for the optimization of distribution-network feeder configurations. The algorithm starts analysis from HV/MV substations with all loads (MV/LV substations) being disconnected and picks up loads that result in minimal incremental losses. Optimality is always assured by checking on relationships correlating currents and paths, using the concept of dynamic programming and performing configuration changes whenever required. The algorithm relies on the comparison of the incremental losses brought by the addition of each and every load to the network. Quadratic and linear relationships between load currents and paths form the basis of the decisions made for the connections. The algorithm is illustrated with the help of a detailed numerical example. Geographic information systems software, ArcView, was used as the developing tool. [ABSTRACT FROM PUBLISHER]