Restless Legs Syndrome: Current Concepts about Disease Pathophysiology

Background: In the past few decades, much has been learned about the pathophysiology of restless legs syndrome (RLS). Investigators have studied neuropathology, imaging, electrophysiology, and genetics of RLS, identifying brain regions and biological systems affected in RLS. This manuscript will review RLS pathophysiology literature, examining the RLS state through consideration of the neuroanatomy, then the biological, organ, and genetic systems. Methods: Pubmed (1966 to April 2016) was searched for the term “restless legs syndrome” cross-referenced with “pathophysiology,” “pathogenesis,” “pathology,” or “imaging.” English language papers were reviewed. Studies that focused on RLS in relation to another disease were not reviewed. Results: Although there are no gross structural brain abnormalities in RLS, widespread brain areas are activated, including the pre- and post-central gyri, cingulate cortex, thalamus, and cerebellum. Pathologically, the most consistent finding is striatal iron deficiency in RLS patients. A host of other biological systems are also altered in RLS, including the dopaminergic, oxygen-sensing, opioid, glutamatergic, and serotonergic systems. Polymorphisms in genes including BTBD9 and MEIS1 are associated with RLS. Discussion: RLS is a neurologic sensorimotor disorder that involves pathology, most notably iron deficiency, in motor and sensory brain areas. Brain areas not subserving movement or sensation such as the cingulate cortex and cerebellum are also involved. Other biological systems including the dopaminergic, oxygen-sensing, opioid, glutamatergic, and serotonergic systems are involved. Further research is needed to determine which of these anatomic locations or biological systems are affected primarily, and which are affected in a secondary response

Formulation, Casting, and Evaluation of Paraffin-Based Solid Fuels Containing Energetic and Novel Additives for Hybrid Rockets

This investigation studied the inclusion of various additives to paraffin wax for use in a hybrid rocket motor. Some of the paraffin-based fuels were doped with various percentages of LiAlH4 (up to 10%). Addition of LiAlH4 at 10% was found to increase regression rates between 7 - 10% over baseline paraffin through tests in a gaseous oxygen hybrid rocket motor. Mass burn rates for paraffin grains with 10% LiAlH4 were also higher than those of the baseline paraffin. RDX was also cast into a paraffin sample via a novel casting process which involved dissolving RDX into dimethylformamide (DMF) solvent and then drawing a vacuum on the mixture of paraffin and RDX/DMF in order to evaporate out the DMF. It was found that although all DMF was removed, the process was not conducive to generating small RDX particles. The slow boiling generated an inhomogeneous mixture of paraffin and RDX. It is likely that superheating the DMF to cause rapid boiling would likely reduce RDX particle sizes. In addition to paraffin/LiAlH4 grains, multi-walled carbon nanotubes (MWNT) were cast in paraffin for testing in a hybrid rocket motor, and assorted samples containing a range of MWNT percentages in paraffin were imaged using SEM. The fuel samples showed good distribution of MWNT in the paraffin matrix, but the MWNT were often agglomerated, indicating that a change to the sonication and mixing processes were required to achieve better uniformity and debundled MWNT. Fuel grains with MWNT fuel grains had slightly lower regression rate, likely due to the increased thermal conductivity to the fuel subsurface, reducing the burning surface temperature

The DEEP2 Galaxy Redshift Survey: Clustering of Groups and Group Galaxies at z~1

We study the clustering properties of groups and of galaxies in groups in the DEEP2 Galaxy Redshift Survey dataset at z~1. Four clustering measures are presented: 1) the group correlation function for 460 groups with estimated velocity dispersions of sigma>200 km/s, 2) the galaxy correlation for the full galaxy sample, using a flux-limited sample of 9800 objects between 0.7<z<1.0, 3) the galaxy correlation for galaxies in groups, and 4) the group-galaxy cross-correlation function. Using the observed number density and clustering amplitude of the groups, the estimated minimum group dark matter halo mass is M_min~6 10^12 h^-1 M_Sun for a flat LCDM cosmology. Groups are more clustered than galaxies, with a relative bias of b=1.7 +/-0.04 on scales r_p=0.5-15 Mpc/h. Galaxies in groups are also more clustered than the full galaxy sample, with a scale-dependent relative bias which falls from b~2.5 +/-0.3 at r_p=0.1 Mpc/h to b~1 +/-0.5 at r_p=10 Mpc/h. The correlation functions for all galaxies and galaxies in groups can be fit by a power-law on scales r_p=0.05-20 Mpc/h. We empirically measure the contribution to the projected correlation function for galaxies in groups from a `one-halo' term and a `two-halo' term by counting pairs of galaxies in the same or in different groups. The projected cross-correlation between shows that red galaxies are more centrally concentrated in groups than blue galaxies at z~1. DEEP2 galaxies in groups appear to have a shallower radial distribution than that of mock galaxy catalogs made from N-body simulations, which assume a central galaxy surrounded by satellite galaxies with an NFW profile. We show that the clustering of galaxies in groups can be used to place tighter constraints on the halo model than can be gained from using the usual galaxy correlation function alone.Comment: 22 pages, 12 figures, in emulateapj format, accepted to ApJ, minor changes made to match published versio

The DEEP2 Galaxy Redshift Survey: Color and Luminosity Dependence of Galaxy Clustering at z~1

We present measurements of the color and luminosity dependence of galaxy clustering at z~1 in the DEEP2 Galaxy Redshift Survey. Using volume-limited subsamples in bins of both color and luminosity, we find that: 1) The clustering dependence is much stronger with color than with luminosity and is as strong with color at z~1 as is found locally. We find no dependence of the clustering amplitude on color for galaxies on the red sequence, but a significant dependence on color for galaxies within the blue cloud. 2) For galaxies in the range L/L*~0.7-2, a stronger large-scale luminosity dependence is seen for all galaxies than for red and blue galaxies separately. The small-scale clustering amplitude depends significantly on luminosity for blue galaxies, with brighter samples having a stronger rise on scales r_p<0.5 Mpc/h. 3) Redder galaxies exhibit stronger small-scale redshift-space distortions ("fingers of god"), and both red and blue populations show large-scale distortions in xi(r_p,pi) due to coherent infall. 4) While the clustering length, r_0, increases smoothly with galaxy color (in narrow bins), its power-law exponent, gamma, exhibits a sharp jump from the blue cloud to the red sequence. The intermediate color `green' galaxy population likely includes transitional galaxies moving from the blue cloud to the red sequence; on large scales green galaxies are as clustered as red galaxies but show infall kinematics and a small-scale correlation slope akin to the blue galaxy population. 5) We compare our results to a semi-analytic galaxy formation model applied to the Millenium Run simulation. Differences between the data and the model suggest that in the model star formation is shut down too efficiently in satellite galaxies.Comment: 28 pages, 17 figures, emulateapj format, accepted to ApJ, updated to match published versio

The Determining Risk of Vascular Events by Apnea Monitoring (DREAM) Study: Design, Rationale and Methods

Purpose The goal of the Determining Risk of Vascular Events by Apnea Monitoring (DREAM) study is to develop a prognostic model for cardiovascular outcomes, based on physiologic variables—related to breathing, sleep architecture, and oxygenation—measured during polysomnography in US veterans. Methods The DREAM study is a multi-site, retrospective observational cohort study conducted at three Veterans Affairs (VA) centers (West Haven, CT; Indianapolis, IN; Cleveland, OH). Veterans undergoing polysomnography between January 1, 2000 and December 31, 2004 were included based on referral for evaluation of sleep-disordered breathing, documented history and physical prior to sleep testing, and ≥2-h sleep monitoring. Demographic, anthropomorphic, medical, medication, and social history factors were recorded. Measures to determine sleep apnea, sleep architecture, and oxygenation were recorded from polysomnography. VA Patient Treatment File, VA–Medicare Data, Vista Computerized Patient Record System, and VA Vital Status File were reviewed on dates subsequent to polysomnography, ranging from 0.06 to 8.8 years (5.5 ± 1.3 years; mean ± SD). Results The study population includes 1840 predominantly male, middle-aged veterans. As designed, the main primary outcome is the composite endpoint of acute coronary syndrome, stroke, transient ischemic attack, or death. Secondary outcomes include incidents of neoplasm, congestive heart failure, cardiac arrhythmia, diabetes, depression, and post-traumatic stress disorder. Laboratory outcomes include measures of glycemic control, cholesterol, and kidney function. (Actual results are pending.) Conclusions This manuscript provides the rationale for the inclusion of veterans in a study to determine the association between physiologic sleep measures and cardiovascular outcomes and specifically the development of a corresponding outcome-based prognostic model

Spectroscopic Target Selection in the Sloan Digital Sky Survey: The Quasar Sample

We describe the algorithm for selecting quasar candidates for optical spectroscopy in the Sloan Digital Sky Survey. Quasar candidates are selected via their non-stellar colors in "ugriz" broad-band photometry, and by matching unresolved sources to the FIRST radio catalogs. The automated algorithm is sensitive to quasars at all redshifts lower than z=5.8. Extended sources are also targeted as low-redshift quasar candidates in order to investigate the evolution of Active Galactic Nuclei (AGN) at the faint end of the luminosity function. Nearly 95% of previously known quasars are recovered (based on 1540 quasars in 446 square degrees). The overall completeness, estimated from simulated quasars, is expected to be over 90%, whereas the overall efficiency (quasars:quasar candidates) is better than 65%. The selection algorithm targets ultraviolet excess quasars to i^*=19.1 and higher-redshift (z>3) quasars to i^*=20.2, yielding approximately 18 candidates per square degree. In addition to selecting ``normal'' quasars, the design of the algorithm makes it sensitive to atypical AGN such as Broad Absorption Line quasars and heavily reddened quasars.Comment: 62 pages, 15 figures (8 color), 8 tables. Accepted by AJ. For a version with higher quality color figures, see http://archive.stsci.edu/sdss/quasartarget/RichardsGT_qsotarget.preprint.p

The DEEP2 Galaxy Redshift Survey: The Evolution of Void Statistics from z~1 to z~0

We present measurements of the void probability function (VPF) at z~1 using data from the DEEP2 Redshift Survey and its evolution to z~0 using data from the Sloan Digital Sky Survey (SDSS). We measure the VPF as a function of galaxy color and luminosity in both surveys and find that it mimics trends displayed in the two-point correlation function, $\xi$; namely that samples of brighter, red galaxies have larger voids (i.e. are more strongly clustered) than fainter, blue galaxies. We also clearly detect evolution in the VPF with cosmic time, with voids being larger in comoving units at z~0. We find that the reduced VPF matches the predictions of a `negative binomial' model for galaxies of all colors, luminosities, and redshifts studied. This model lacks a physical motivation, but produces a simple analytic prediction for sources of any number density and integrated two-point correlation function, \bar{\xi}. This implies that differences in the VPF across different galaxy populations are consistent with being due entirely to differences in the population number density and \bar{\xi}. The robust result that all galaxy populations follow the negative binomial model appears to be due to primarily to the clustering of dark matter halos. The reduced VPF is insensitive to changes in the parameters of the halo occupation distribution, in the sense that halo models with the same \bar{\xi} will produce the same VPF. For the wide range of galaxies studied, the VPF therefore does not appear to provide useful constraints on galaxy evolution models that cannot be gleaned from studies of \bar{\xi} alone. (abridged)Comment: 17 pages, 15 figures, ApJ accepte

Urges to Move and Other Motivation States for Physical Activity in Clinical and Healthy Populations: A Scoping Review Protocol

[EN] Motivation for bodily movement, physical activity and exercise varies from moment to moment. These motivation states may be “affectively-charged,” ranging from instances of lower tension (e.g., desires, wants) to higher tension (e.g., cravings and urges). Currently, it is not known how often these states have been investigated in clinical populations (e.g., eating disorders, exercise dependence/addiction, Restless Legs Syndrome, diabetes, obesity) vs. healthy populations (e.g., in studies of motor control; groove in music psychology). The objective of this scoping review protocol is to quantify the literature on motivation states, to determine what topical areas are represented in investigations of clinical and healthy populations, and to discover pertinent details, such as instrumentation, terminology, theories, and conceptual models, correlates and mechanisms of action. Iterative searches of scholarly databases will take place to determine which combination of search terms (e.g., “motivation states” and “physical activity”; “desire to be physically active,” etc.) captures the greatest number of relevant results. Studies will be included if motivation states for movement (e.g., desires, urges) are specifically measured or addressed. Studies will be excluded if referring to motivation as a trait. A charting data form was developed to scan all relevant documents for later data extraction. The primary outcome is simply the extent of the literature on the topic. Results will be stratified by population/condition. This scoping review will unify a diverse literature, which may result in the creation of unique models or paradigms that can be utilized to better understand motivation for bodily movement and exercise.GA was supported by a fellowship from the Office of Academic Affiliations at the United States Veterans Health Administration, a Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award, Bank of America, N.A., Trustee, and American Heart Association Grant #852679 (GA, 2021–2024).We would like to thank Melissa Eden, Ph.D. (Hanover College, IN) for her valuable assistance in refining aspects of the search strategy. Khristdman Cavalcanti helped with technical aspects of the study. Sunao Akashi Slayton, PharmD BCOP (Smilow Cancer Hospital, Yale – New Haven Hospital, CT) evaluated clinical information and provided nomenclatur

Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active and Recently Retired National Football League Players

Importance: Microglia, the resident immune cells of the central nervous system, play an important role in the brain\u27s response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. Objective: To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. Design, Setting, and Participants: This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. Main Outcomes and Measures: Positron emission tomography-based regional measures of TSPO using [11C]DPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. Results: The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using [11C]DPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P \u3c .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. Conclusions and Relevance: The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms

Draft Genome of the Filarial Nematode Parasite \u3ci\u3eBrugia malayi\u3c/i\u3e

Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design