Intention Tremor and Deficits of Sensory Feedback Control in Multiple Sclerosis: a Pilot Study

Background Intention tremor and dysmetria are leading causes of upper extremity disability in Multiple Sclerosis (MS). The development of effective therapies to reduce tremor and dysmetria is hampered by insufficient understanding of how the distributed, multi-focal lesions associated with MS impact sensorimotor control in the brain. Here we describe a systems-level approach to characterizing sensorimotor control and use this approach to examine how sensory and motor processes are differentially impacted by MS. Methods Eight subjects with MS and eight age- and gender-matched healthy control subjects performed visually-guided flexion/extension tasks about the elbow to characterize a sensory feedback control model that includes three sensory feedback pathways (one for vision, another for proprioception and a third providing an internal prediction of the sensory consequences of action). The model allows us to characterize impairments in sensory feedback control that contributed to each MS subject’s tremor. Results Models derived from MS subject performance differed from those obtained for control subjects in two ways. First, subjects with MS exhibited markedly increased visual feedback delays, which were uncompensated by internal adaptive mechanisms; stabilization performance in individuals with the longest delays differed most from control subject performance. Second, subjects with MS exhibited misestimates of arm dynamics in a way that was correlated with tremor power. Subject-specific models accurately predicted kinematic performance in a reach and hold task for neurologically-intact control subjects while simulated performance of MS patients had shorter movement intervals and larger endpoint errors than actual subject responses. This difference between simulated and actual performance is consistent with a strategic compensatory trade-off of movement speed for endpoint accuracy. Conclusions Our results suggest that tremor and dysmetria may be caused by limitations in the brain’s ability to adapt sensory feedback mechanisms to compensate for increases in visual information processing time, as well as by errors in compensatory adaptations of internal estimates of arm dynamics

A Spectroscopic Study of Field and Runaway OB Stars

Identifying binaries among runaway O- and B-type stars offers valuable insight into the evolution of open clusters and close binary stars. Here we present a spectroscopic investigation of 12 known or suspected binaries among field and runaway OB stars. We find new orbital solutions for five single-lined spectroscopic binaries (HD 1976, HD 14633, HD 15137, HD 37737, and HD 52533), and we classify two stars thought to be binaries (HD 30614 and HD 188001) as single stars. In addition, we reinvestigate their runaway status using our new radial velocity data with the UCAC2 proper motion catalogs. Seven stars in our study appear to have been ejected from their birthplaces, and at least three of these runaways are spectroscopic binaries and are of great interest for future study.Comment: 21 pages, 1 figure, 7 tables; Accepted to Ap

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Balance of Power and the Propensity of Conflict

We study the role of an imbalance in fighting strengths when players bargain in the shadow of conflict. Our experimental results suggest: In a simple bargaining game with an exogenous mediation proposal, the likelihood of conflict is independent of the balance of power. If bargaining involves endogenous demand choices, however, the likelihood of conflict is higher if power is more imbalanced. Even though endogenous bargaining outcomes reflect the players' unequal fighting strengths, strategic uncertainty causes outcomes to be most efficient when power is balanced. In turn, the importance of exogenous mediation proposals depends on the balance of power

Superoxide Dismutase Mimetic GC4419 Enhances the Oxidation of Pharmacological Ascorbate and Its Anticancer Effects in an H2O2-Dependent Manner

Lung cancer, together with head and neck cancer, accounts for more than one-fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH−) represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer effects via metal-catalyzed oxidation to form H2O2. Mn(III)-porphyrins possessing superoxide dismutase (SOD) mimetic activity have been shown to increase the rate of oxidation of AscH−, enhancing the anti-tumor effects of AscH− in several cancer types. The current study demonstrates that the Mn(II)-containing pentaazamacrocyclic selective SOD mimetic GC4419 may serve as an AscH−/O2•− oxidoreductase as evidenced by the increased rate of oxygen consumption, steady-state concentrations of ascorbate radical, and H2O2 production in complete cell culture media. GC4419, but not CuZnSOD, was shown to significantly enhance the toxicity of AscH− in H1299, SCC25, SQ20B, and Cal27 cancer cell lines. This enhanced cancer cell killing was dependent upon the catalytic activity of the SOD mimetic and the generation of H2O2, as determined using conditional overexpression of catalase in H1299T cells. GC4419 combined with AscH− was also capable of enhancing radiation-induced cancer cell killing. Currently, AscH− and GC4419 are each being tested separately in clinical trials in combination with radiation therapy. Data presented here support the hypothesis that the combination of GC4419 and AscH− may provide an effective means by which to further enhance radiation therapy responses

Application of SWAN+ADCIRC to tide-surge and wave simulation in Gulf of Maine during Patriot's Day storm

The southern coast of the Gulf of Maine in the United States is prone to flooding caused by nor’easters. A state-of-the-art fully-coupled model, the Simulating WAves Nearshore (SWAN) model with unstructured grids and the ADvanced CIRCulation (ADCIRC) model, was used to study the hydrodynamic response in the Gulf of Maine during the Patriot’s Day storm of 2007, a notable example of nor’easters in this area. The model predictions agree well with the observed tide-surges and waves during this storm event. Waves and circulation in the Gulf of Maine were analyzed. The Georges Bank plays an important role in dissipating wave energy through the bottom friction when waves propagate over the bank from offshore to the inner gulf due to its shallow bathymetry. Wave energy dissipation results in decreasing significant wave height (SWH) in the cross-bank direction and wave radiation stress gradient, which in turn induces changes in currents. While the tidal currents are dominant over the Georges Bank and in the Bay of Fundy, the residual currents generated by the meteorological forcing and waves are significant over the Georges Bank and in the coastal area and can reach 0.3 m/s and 0.2 m/s, respectively. In the vicinity of the coast, the longshore current generated by the surface wind stress and wave radiation stress acting parallel to the coastline is inversely proportional to the water depth and will eventually be limited by the bottom friction. The storm surge level reaches 0.8 m along the western periphery of the Gulf of Maine while the wave set-up due to radiation stress variation reaches 0.2 m. Therefore, it is significant to coastal flooding