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Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
A nationwide survey indicated that screening for asymptomatic carriers of C. difficile is an uncommon practice in US healthcare settings. Better understanding of the role of asymptomatic carriage in C. difficile transmission, and of the measures available to reduce that risk, are needed to inform best practices regarding the management of carriers.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Development involves synergistic interplay among genotypes and the physical and cultural environments, and integrating genetics into experimental designs that manipulate the environment can improve understanding of developmental psychopathology and intervention efficacy. Consistent with differential susceptibility theory, individuals can vary in their sensitivity to environmental conditions including intervention for reasons including their genotype. As a consequence, understanding genetic influences on intervention response is critical. Empirically, we tested an interaction between a genetic index representing sensitivity to the environment and the Family Check-Up intervention. Participants were drawn from the Early Steps Multisite randomized prevention trial that included a low-income and racially/ethnically diverse sample of children and their families followed longitudinally (n = 515). As hypothesized, polygenic sensitivity to the environment moderated the effects of the intervention on 10-year-old children's symptoms of internalizing psychopathology, such that children who were genetically sensitive and were randomly assigned to the intervention had fewer symptoms of child psychopathology than genetically sensitive children assigned to the control condition. A significant difference in internalizing symptoms assessed with a clinical interview emerged between the intervention and control groups for those 0.493 SD above the mean on polygenic sensitivity, or 25% of the sample. Similar to personalized medicine, it is time to understand individual and sociocultural differences in treatment response and individualize psychosocial interventions to reduce the burden of child psychopathology and maximize well-being for children growing up in a wide range of physical environments and cultures.
We review the early history of the general theory of relativity and its subsequent decline to the backwaters of physics and astronomy. We describe the renaissance of the theory during the 1960s and the renewed effort to subject it to experimental tests using laboratory experiments, the solar system, binary pulsars, and finally in 2015, gravitational waves. We then discuss future directions for experimental tests in the strong-field and dynamical regimes.
We describe the general characteristics of metric theories of gravity, and review the equations of non-gravitational physics in curved spacetime. We introduce the Strong Equivalence Principle, which generalizes the Einstein Equivalence Principle to situations where local gravitational interactions are important, and discuss why general relativity may be unique in conforming to this principle.
We discuss tests of the Strong Equivalence Principle. We derive the observable consequences of the Nordtvedt effect, a violation of the equality of acceleration of massive, self-gravitating bodies, that occurs in many alternative theories of gravity, although not in general relativity. We discuss the bounds obtained on this effect via lunar laser ranging, and via measurements of pulsar-white dwarf binary systems. We derive a number of observable consequences of preferred-frame effects in binary orbits and in the structure of self-gravitating bodies, and review the bounds that have been placed on the relevant PPN parameters by a wide range of observations.
We discuss a range of metric theories of gravity and their post-Newtonian limits. We begin with a general recipe for calculating the post-Newtonian limit in generic metric theories, and then turn to specific theories. Included are general relativity, scalar-tensor theories, vector-tensor theories (including Einstein-Aether and Khronometric theories), tensor-vector-scalar theories (including TeVeS), quadratic gravity theories (including Chern-Simons theory), and massive gravity theories. We also review the fate of theories of gravity that were featured in the first edition of this book, but that are no longer considered viable or interesting, including Whitehead’s theory and Rosen’s bimetric theory.
We begin with a historical overview of the problem of motion and gravitational radiation in general relativity, and then describe the current status of gravitational wave detection, based upon laser interferometry and pulsar timing. We discuss the properties of gravitational waves in alternative theories of gravity, including their speed and polarization states. We discuss the general method for analysing the generation of gravitational waves, primarily in compact binary systems, and discuss the results for the gravitational waveform, energy and angular momentum flux, and gravitational radiation reaction in general relativity and scalar-tensor theories.
We develop the parametrized post-Newtonian (PPN) formalism, which encompasses the weak-field, slow-motion regime, known as the post-Newtonian limit, of a wide range of metric theories of gravity. Ten PPN parameters are introduced, whose values depend upon the theory of gravity under study. We show that general properties of metric theories of gravity may be reflected in specific values of the PPN parameters, including the presence or absence of a preferred universal frame of reference, and the presence or absence of global conservation laws for energy, momentum and angular momentum.
We discuss the foundations of general relativity and all modern gravitational theories, based on the Einstein Equivalence Principle (EEP). We show that this principle is the basis for all metric theories of gravity including general relativity, in which gravity is a consequence of spacetime geometry. We review experimental test of the three pieces of EEP, the Weak Equivalence Principle, Local Lorentz Invariance and Local Position Invariance, and describe a number of general theoretical frameworks used to analyse EEP and its consequences.
We describe experimental tests of the effects of spinning bodies, which include precessions of spins as well as orbital perturbations. We give a technical and historical review of Gravity Probe B, a space experiment to measure the precession of orbiting gyroscopes, and the LAGEOS measurements of orbital perturbations, induced by the spinning Earth. We review experimental tests of post-Newtonian conservation laws, and the bounds on the relevant PPN parameters.
We describe tests of gravitational theory in the strong-field and dynamical regimes. Beginning with binary pulsars, we carry out an arrival-time analysis that reveals the relativistic effects on the time of arrival of radio pulses measured by an observer. We then describe the Hulse-Taylor binary pulsar, the double pulsar, a number of pulsars with white-dwarf companions, and the pulsar in a triple system, and describe the tests of gravitational theories that have been carried out using them. We describe the inspiral of compact binaries in general relativity and scalar-tensor theories, and the tests of gravitational theory that have been carried out using data from the gravitational wave detections of 2015 - 2017. We discuss future tests of general relativity in the strong-field regime, including tests using observations of stars orbiting the black hole at the center of the galaxy, tests involving accretion of matter onto black holes and neutron stars, and cosmological tests.