203 research outputs found

    The Relationship between Gratitude, Wellbeing, Spirituality, and Experiencing Meaningful Work

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    Poor mental wellbeing not only affects an individual and their family, but it also affects the workplace and the society as a whole. Consequently, it is crucial to investigate approaches that can promote a positive mindset in order to enhance wellbeing. This study aimed to explore the association between gratitude, wellbeing, spirituality, and experiencing meaningful work. A sample of 197 participants (69.5% female) completed measures of gratitude, experiencing meaningful work, spirituality, and several wellbeing indices. Gratitude was significantly positively associated with happiness, life satisfaction, flourishing, positive affect, spirituality, and experiencing meaningful work. A mediation analysis revealed that the relationship between wellbeing and experiencing meaningful work was partially mediated by gratitude. Additionally, spirituality did not moderate the relationship between gratitude and experiencing meaningful work. Overall, the findings indicate that fostering a grateful mindset could enhance wellbeing and work engagement, which in turn could lead to the experience of meaningful work

    Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

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    Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

    Urban Air Mobility Airspace Integration Concepts and Considerations

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    Urban Air Mobility (UAM) - defined as safe and efficient air traffic operations in a metropolitan area for manned aircraft and unmanned aircraft systems - is being researched and developed by industry, academia, and government. Significant resources have been invested toward cultivating an ecosystem for Urban Air Mobility that includes manufacturers of electric vertical takeoff and landing aircraft, builders of takeoff and landing areas, and researchers of the airspace integration concepts, technologies, and procedures needed to conduct Urban Air Mobility operations safely and efficiently alongside other airspace users. This paper provides high-level descriptions of both emergent and early expanded operational concepts for Urban Air Mobility that NASA is developing. The scope of this work is defined in terms of missions, aircraft, airspace, and hazards. Past and current Urban Air Mobility operations are also reviewed, and the considerations for the data exchange architecture and communication, navigation, and surveillance requirements are also discussed. This paper will serve as a starting point to develop a framework for NASA's Urban Air Mobility airspace integration research and development efforts with partners and stakeholders that could include fast-time simulations, human-in-the-loop (HITL) simulations, and flight demonstrations

    The CIP2A–TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer

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    BRCA1/2-mutated cancer cells adapt to the genome instability caused by their deficiency in homologous recombination (HR). Identification of these adaptive mechanisms may provide therapeutic strategies to target tumors caused by the loss of these genes. In the present study, we report genome-scale CRISPR-Cas9 synthetic lethality screens in isogenic pairs of BRCA1- and BRCA2-deficient cells and identify CIP2A as an essential gene in BRCA1- and BRCA2-mutated cells. CIP2A is cytoplasmic in interphase but, in mitosis, accumulates at DNA lesions as part of a complex with TOPBP1, a multifunctional genome stability factor. Unlike PARP inhibition, CIP2A deficiency does not cause accumulation of replication-associated DNA lesions that require HR for their repair. In BRCA-deficient cells, the CIP2A-TOPBP1 complex prevents lethal mis-segregation of acentric chromosomes that arises from impaired DNA synthesis. Finally, physical disruption of the CIP2A-TOPBP1 complex is highly deleterious in BRCA-deficient tumors, indicating that CIP2A represents an attractive synthetic lethal therapeutic target for BRCA1- and BRCA2-mutated cancers

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics

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    We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to the common ‘spaghetti-like’ structures but to dense matted deposits. Type 2 diabetes is a known inflammatory disease. In the present work, we found that the axial ratio of the erythrocytes of poorly controlled (as suggested by increased HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin morphologies were again highly aberrant. As judged by scanning electron microscopy and in the atomic force microscope, these could be reversed, to some degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox (DFX). As well as their demonstrated diagnostic significance, these morphological indicators may have prognostic value.Biotechnology and Biological Sciences Research Council (grant BB/L025752/1) as well as the National Research Foundation (NRF) of South Africa.http://www.cardiab.com/hb201

    The NANOGrav 15-year Data Set: Search for Anisotropy in the Gravitational-Wave Background

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    The North American Nanohertz Observatory for Gravitational Waves (NANOGrav) has reported evidence for the presence of an isotropic nanohertz gravitational wave background (GWB) in its 15 yr dataset. However, if the GWB is produced by a population of inspiraling supermassive black hole binary (SMBHB) systems, then the background is predicted to be anisotropic, depending on the distribution of these systems in the local Universe and the statistical properties of the SMBHB population. In this work, we search for anisotropy in the GWB using multiple methods and bases to describe the distribution of the GWB power on the sky. We do not find significant evidence of anisotropy, and place a Bayesian 95%95\% upper limit on the level of broadband anisotropy such that (Cl>0/Cl=0)<20%(C_{l>0} / C_{l=0}) < 20\%. We also derive conservative estimates on the anisotropy expected from a random distribution of SMBHB systems using astrophysical simulations conditioned on the isotropic GWB inferred in the 15-yr dataset, and show that this dataset has sufficient sensitivity to probe a large fraction of the predicted level of anisotropy. We end by highlighting the opportunities and challenges in searching for anisotropy in pulsar timing array data.Comment: 19 pages, 11 figures; submitted to Astrophysical Journal Letters as part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave Background. For questions or comments, please email [email protected]

    The NANOGrav 15-Year Data Set: Detector Characterization and Noise Budget

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    Pulsar timing arrays (PTAs) are galactic-scale gravitational wave detectors. Each individual arm, composed of a millisecond pulsar, a radio telescope, and a kiloparsecs-long path, differs in its properties but, in aggregate, can be used to extract low-frequency gravitational wave (GW) signals. We present a noise and sensitivity analysis to accompany the NANOGrav 15-year data release and associated papers, along with an in-depth introduction to PTA noise models. As a first step in our analysis, we characterize each individual pulsar data set with three types of white noise parameters and two red noise parameters. These parameters, along with the timing model and, particularly, a piecewise-constant model for the time-variable dispersion measure, determine the sensitivity curve over the low-frequency GW band we are searching. We tabulate information for all of the pulsars in this data release and present some representative sensitivity curves. We then combine the individual pulsar sensitivities using a signal-to-noise-ratio statistic to calculate the global sensitivity of the PTA to a stochastic background of GWs, obtaining a minimum noise characteristic strain of 7×10157\times 10^{-15} at 5 nHz. A power law-integrated analysis shows rough agreement with the amplitudes recovered in NANOGrav's 15-year GW background analysis. While our phenomenological noise model does not model all known physical effects explicitly, it provides an accurate characterization of the noise in the data while preserving sensitivity to multiple classes of GW signals.Comment: 67 pages, 73 figures, 3 tables; published in Astrophysical Journal Letters as part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave Background. For questions or comments, please email [email protected]
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