A Vicious Cycle of Fear of Falling Avoidance Behavior in Parkinson’s Disease: A Path Analysis

Background: Postural instability (PI) in Parkinson\u27s disease (PD) is associated with several negative downstream consequences. Objective: The purpose was to explore the validity of a theoretical model of these downstream consequences arranged in a vicious cycle wherein PI leads to decreased balance confidence, which in turn leads to increased fear of falling (FOF) avoidance behavior, which in turn leads to decreased physical conditioning, which then feeds back and negatively affects PI. Methods: A path analysis of cross-sectional data from 55 participants with PD was conducted. The four constructs in the model connected in succession were: 1. PI (principal components analysis (PCA) composite of the Unified Parkinson\u27s Disease Rating Scale PI and Gait Difficulty score, Timed Up and Go test, and Berg Balance Scale); 2. balance confidence (Activities-Specific Balance Confidence Scale); 3. FOF avoidance behavior (PCA composite of the FOF Avoidance Behavior Questionnaire and average number of steps per day); and, 4. physical conditioning (2-Minute Step Test). Results: The path model was an excellent fit to the data, χ2 (7) = 7.910, p =.341, CFI = 0.985, TLI = 0.968, RMSEA = 0.049 (90% CI: 0.000 to 0.179). The moderate to strong and uniformly significant parameter estimates were −0.519, −0.651, −0.653, and −0.570, respectively (ps \u3c 0.01). Conclusions: PI directly and inversely predicted balance confidence, which in turn directly and inversely predicted FOF avoidance behavior. Furthermore, FOF avoidance behavior directly and inversely predicted physical conditioning, which directly and inversely predicted PI, thereby closing the cycle. These findings highlight the downstream consequences of PI in PD and support the notion of a vicious cycle of FOF avoidance behavior

Study of damage control systems for space station

Damage control systems for detecting and locating overboard and onboard leak and damage modes on space station

Optical Instrument Thermal Control on the Large Ultraviolet/Optical/Infrared Surveyor

The Large Ultraviolet/Optical/Infrared Surveyor (LUVOIR) is a multi-wavelength observatory commissioned by NASA as one of four large mission concept studies for the Astro2020 Decadal Survey. Two concepts are under study which bound a range of cost, risk, and scientific return: an 8-meter diameter unobscured segmented aperture primary mirror and a 15-meter segmented aperture primary mirror. Each concept carries with it an accompanying suite of instruments. The Extreme Coronagraph for Living Planetary Systems (ECLIPS) is a near-ultraviolet (NUV) / optical / near-infrared (NIR) coronagraph; the LUVOIR Ultraviolet Multi-object Spectrograph (LUMOS) provides multi-object imaging spectroscopy in the 100-400 nanometer ultraviolet (UV) range; and the High Definition Imager (HDI) is a wide field-of-view near-UV / optical / near-IR camera that can also perform astrometry. The 15-meter concept also contains an additional instrument, Pollux, which is a high-resolution UV spectro-polarimeter. While the observatory is nominally at a 270 Kelvin operational temperature, the requirements of imaging in both IR and UV require separate detectors operating at different temperature regimes, each with stringent thermal stability requirements. The change in observatory size requires two distinct thermal designs per instrument. In this current work, the thermal architecture is presented for each instrument suite. We describe here the efforts made to achieve the target operational temperatures and stabilities with passive thermal control methods. Additional discussion will focus on how these instrument thermal designs impact the overall system-level architecture of the observatory and indicate the thermal challenges for hardware implementation

Three flavor neutrino oscillation analysis of atmospheric neutrinos in Super-Kamiokande

We report on the results of a three-flavor oscillation analysis using Super-Kamiokande~I atmospheric neutrino data, with the assumption of one mass scale dominance ($\Delta m_{12}^2$$=$0). No significant flux change due to matter effect, which occurs when neutrinos propagate inside the Earth for $\theta_{13}$$\neq$0, has been seen either in a multi-GeV $\nu_e$-rich sample or in a $\nu_\mu$-rich sample. Both normal and inverted mass hierarchy hypotheses are tested and both are consistent with observation. Using Super-Kamiokande data only, 2-dimensional 90 % confidence allowed regions are obtained: mixing angles are constrained to $\sin^2\theta_{13} < 0.14$ and $0.37 < \sin^2\theta_{23} < 0.65$ for the normal mass hierarchy. Weaker constraints, $\sin^2\theta_{13} < 0.27$ and $0.37 < \sin^2\theta_{23} < 0.69$, are obtained for the inverted mass hierarchy case.Comment: 7 figures, 3 table

Study of Non-Standard Neutrino Interactions with Atmospheric Neutrino Data in Super-Kamiokande I and II

In this paper we study non-standard neutrino interactions as an example of physics beyond the standard model using atmospheric neutrino data collected during the Super-Kamiokande I(1996-2001) and II(2003-2005) periods. We focus on flavor-changing-neutral-currents (FCNC), which allow neutrino flavor transitions via neutral current interactions, and effects which violate lepton non-universality (NU) and give rise to different neutral-current interaction-amplitudes for different neutrino flavors. We obtain a limit on the FCNC coupling parameter, varepsilon_{mu tau}, |varepsilon_{mu tau}|<1.1 x 10^{-2} at 90%C.L. and various constraints on other FCNC parameters as a function of the NU coupling, varepsilon_{e e}. We find no evidence of non-standard neutrino interactions in the Super-Kamiokande atmospheric data.Comment: 12 Pages, 14 figures. To be submitted to Phys. Rev.

Evidence for the Appearance of Atmospheric Tau Neutrinos in Super-Kamiokande

Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 \pm 0.35 \ (stat) {\}^{+0.14}_{-0.12}\ (syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8$\sigma$ level. We estimate that 180.1 \pm 44.3\ (stat) {\}^{+17.8}_{-15.2}\ (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.Comment: 7 pages, 4 figures. This is the version as published in Physical Review Letters including the supplemental figure. A typographical error in the description of figure 3 is also correcte

Malic enzyme 1 absence in synovial sarcoma shifts antioxidant system dependence and increases sensitivity to ferroptosis induction with ACXT-3102

PURPOSE: To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis. EXPERIMENTAL DESIGN: ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings. The impact of ME1 absence on SS redox homeostasis was evaluated by metabolomics, cell death assays with inhibitors of antioxidant systems, and measurements of intracellular reactive oxygen species (ROS). The susceptibility of ME1-null SS to ferroptosis induction was interrogated in vitro and in vivo. RESULTS: ME1 absence in SS was confirmed in clinical samples, SS cell lines, and an SS tumor model. Investigation of SS glucose metabolism revealed that ME1-null cells exhibit higher rates of glycolysis and higher flux of glucose into the pentose phosphate pathway (PPP), which is necessary to produce NADPH. Evaluation of cellular redox homeostasis demonstrated that ME1 absence shifts dependence from the glutathione system to the thioredoxin system. Concomitantly, ME1 absence drives the accumulation of ROS and labile iron. ROS and iron accumulation enhances the susceptibility of ME1-null cells to ferroptosis induction with inhibitors of xCT (erastin and ACXT-3102). In vivo xenograft models of ME1-null SS demonstrate significantly increased tumor response to ACXT-3102 compared with ME1-expressing controls. CONCLUSIONS: These findings demonstrate the translational potential of targeting redox homeostasis in ME1-null cancers and establish the preclinical rationale for a phase I trial of ACXT-3102 in SS patients. See related commentary by Subbiah and Gan, p. 3408

Search for Nucleon Decay into Charged Anti-lepton plus Meson in Super-Kamiokande I and II

Searches for a nucleon decay into a charged anti-lepton (e^+ or {\mu}^+) plus a light meson ({\pi}^0, {\pi}^-, {\eta}, {\rho}^0, {\rho}^-, {\omega}) were performed using the Super-Kamiokande I and II data. Twelve nucleon decay modes were searched for. The total exposure is 140.9 kiloton \cdot years, which includes a 91.7 kiloton \cdot year exposure (1489.2 live days) of Super-Kamiokande-I and a 49.2 kiloton \cdot year exposure (798.6 live days) of Super-Kamiokande-II. The number of candidate events in the data was consistent with the atmospheric neutrino background expectation. No significant evidence for a nucleon decay was observed in the data. Thus, lower limits on the nucleon partial lifetime at 90% confidence level were obtained. The limits range from 3.6 \times 10^31 to 8.2 \times 10^33 years, depending on the decay modes.Comment: 25 pages, 18 figure