Soluble levels of receptor for advanced glycation endproducts and dysfunctional high-density lipoprotein in persons infected with human immunodeficiency virus: ACTG NWCS332.

The role of high-density lipoprotein (HDL) function and advanced glycation end products (AGEs) in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. Both glycation and oxidation (HDLox) are major modifications of HDL that can alter its composition and function. Therefore, we explored the longitudinal association of HDLox with progression of glycation, as evaluated by measurement of circulating forms of receptor for AGE that predict morbidity (soluble Receptors for Advanced Glycation Endproducts [sRAGE], endogenous secretory Receptors for Advanced Glycation Endproducts [esRAGE]), in people with HIV-1 (PWH; HIV-1) and uninfected (HIV-1) individuals.We retrospectively assessed if levels of plasma sRAGE and esRAGE and HDL function (reduced antioxidant function is associated with increased HDL lipid hydroperoxide content; HDLox) in a subset of participants (n = 80) from a prospective 3-year study (AIDS Clinical Trials Group A5078). Primary outcomes were baseline and yearly rates of change over 96 of 144 weeks (Δ) in HDLox in HIV-1 versus uninfected HIV-1 controls (noted as HIV-1).Higher baseline levels of sRAGE in PWH on effective anti-retroviral therapy and with low CVD risk, but not in HIV-1 persons, were independently associated with higher HDLox. EsRAGE, but not sRAGE, had consistent inverse relationships with ΔHDLox in both HIV-1 and HIV-1 persons at baseline. In HIV-1 but not in HIV-1 persons, ΔHDLox had positive and inverse relationships with ΔRAGE and ΔesRAGE, respectively.Glycation and oxidation of HDL may contribute to impaired HDL function present in PWH

Acoustic positioning and tracking in Portsmouth Harbour, New Hampshire

Portsmouth Harbor, New Hampshire, is frequently used as a testing area for multibeam and sidescan sonars, and is the location of numerous ground-truthing studies. Having the ability to accurately position underwater sensors is an important aspect of this type of work. However, underwater positioning in Portsmouth Harbor is challenging. It is relatively shallow, approximately one kilometer wide with depths of less than 25 meters. There is mixing between fresh river water and seawater, which is intensified by high currents and strong tides. This causes a very complicated spatial and temporal sound speed structure. Solutions that use the time-of-arrival of an acoustic pulse to estimate range will require very precise knowledge of the travel paths of the signal in order to separate out issues of multipath arrivals. An alternative solution is to use the phase measurements between closely spaced hydrophones to measure the bearing of an acoustic pinger. By using two bearing measurement devices that are widely separated, the intersection of the two bearings can be used to position the pinger. The advantage of this approach is that the sound speed only needs to be known at the location of the phase measurements. Both time-of-arrival and phase difference systems may encounter difficulties arising from horizontal refraction due to spatially varying sound speed. To ascertain which solution would be optimal in Portsmouth Harbor, the time-of-arrival and phase measurement approaches are being examined individually. Initial field tests have been conducted using a 40 kHz signal to look at bearing accuracy. Using hydrophones that are spaced 2/3 wavelengths apart, the bearing accuracy was found to be 1.25deg for angles up to 20deg from broadside with signal to noise ratios (SNR) greater than 15 dB. The results from the closely spaced hydrophones were used to resolve phase ambiguities, allowing finer bearing measurements to be made between hydrophones spaced 5 wavelengths apart. The fi- ne bearing measurements resulted in a bearing accuracy of 0.3deg for angles up to 20deg from broadside with SNR greater than 15 dB. Field tests planned for summer 2007 will include a more detailed investigation of how the environmental influences affect each of the measurement types including range, signal to noise ratio, currents, and sound speed structure

Is It Lawful and Ethical to Prioritize Racial Minorities for COVID-19 Vaccines?

Coronavirus disease 2019 (COVID-19) has disproportionately affected racial minorities in the United States resulting in higher rates of infection, hospitalization, and death. With a limited supply after the initial approval of a safe and effective vaccine, difficult legal and ethical choices will have to be made on priority access for individuals. The National Academies of Sciences, Engineering, and Medicine (NASEM) has recommended prioritization of racial minorities who are “worse off” socioeconomically and epidemiologically. TheWorld Health Organization (WHO) similarly cautioned that “colorblind” allocation frameworks could perpetuate or exacerbate existing injustices. Both NASEM and WHO urge policy makers to allocate vaccines in ways that reduce unjust health disparities. The ethics and legality of race-based policies in the United States have been fraught with controversy. This Viewpoint considers how COVID-19 vaccine priority allocations could be implemented ethically and legally

State-Dependent Modulation of Visual Evoked Potentials in a Rodent Genetic Model of Electroencephalographic Instability

Despite normal sleep timing and duration, Egr3-deficient (Egr3−/−) mice exhibit electroencephalographic (EEG) characteristics of reduced arousal, including elevated slow wave (1–4 Hz) activity during wakefulness. Here we show that these mice exhibit state-dependent instability in the EEG. Intermittent surges in EEG power were found in Egr3−/− mice during wakefulness and rapid eye movement sleep, most prominently in the beta (15–35 Hz) range compared to wild type (Egr3+/+) mice. Such surges did not coincide with sleep onset, as the surges were not associated with cessation of electromyographic tone. Cortical processing of sensory information by visual evoked responses (VEP) were found to vary as a function of vigilance state, being of higher magnitude during slow wave sleep (SWS) than wakefulness and rapid eye movement sleep. VEP responses were significantly larger during quiet wakefulness than active wakefulness, in both Egr3−/− mice and Egr3+/+ mice. EEG synchronization in the beta range, previously linked to the accumulation of sleep need over time, predicted VEP magnitude. Egr3−/− mice not only displayed elevated beta activity, but in quiet wake, this elevated beta activity coincides with an elevated evoked response similar to that of animals in SWS. These data confirm that (a) VEPs vary as a function of vigilance state, and (b) beta activity in the EEG is a predictor of state-dependent modulation of visual information processing. The phenotype of Egr3−/− mice indicates that Egr3 is a genetic regulator of these phenomena

Rationing Safe and Effective COVID-19 Vaccines: Allocating to States Proportionate to Population May Undermine Commitments to Mitigating Health Disparities

A central goal in the National Academies of Science, Engineering and Medicine’s (NASEM) framework for equitable COVID-19 vaccine allocation is to mitigate existing inequities, particularly those affecting economically worse-off racial and ethnic minorities. The Advisory Committee on Immunization Practice (ACIP) likewise notes that equity demands to “reduce, rather than increase, health disparities in each phase of vaccine distribution”. A crucial question in this regard is how vaccines should be distributed to states. The default is to allocate proportionate to population size. However, this approach risks increasing scarcity for worse-off populations in states where they represent above-average shares. To avoid lower odds of receiving a vaccine for worse-off groups, more vaccines could be given to states with larger shares of worse-off populations, and fewer to ones with smaller shares. We show here the consequences of allocating by these two different approaches

Equitable Allocation of COVID-19 Vaccines: An Analysis of the Initial Allocation Plans of CDC\u27s Jurisdictions with Implications for Disparate Impact Monitoring

Major global and national vaccine allocation guidelines urge planners to allocate vaccines in ways that recognize, and ideally reduce, existing societal inequities within countries. However, allocation plans of the US will be determined individually by each of the CDC’s 64 jurisdictions (states, the District of Columbia, five cities, and territories). We analyzed whether jurisdictions have incorporated novel approaches to reduce inequity, based on plans published by the CDC in early November 2020 (63 summaries [98% of all jurisdictions] and 47 full guidance documents [73% of all, including all 50 states]). Eighteen states adopted a novel proposal to use a disadvantage index to allocate vaccines more equitably, for five types of equity goals: 1) to prioritize disadvantaged groups directly, 2) to define priority groups in phased systems, 3) to plan tailored outreach and communication, 4) to plan the location of dispensing sites and 5) to monitor uptake. Yet just over a third of all states, and only half of the 16 states with the largest shares of disadvantaged populations—where reducing inequity would be most urgent—pursue such goals. While allocation frameworks are still evolving, the plans we analyzed mark important historical and practical benchmarks, and could become firm policy when COVID-19 vaccines are authorized and delivered. Vaccine roll-out poses unprecedented logistical and practical challenges. To minimize the risk that ethics and social justice falls by the wayside in the busy months to come, planners at the federal, state and local levels should carefully consider on what grounds they decline to adopt equity measures that other planners deem important and feasible for defining priority populations, designing allocation quotas, and just as critical, enabling, and monitoring, uptake

The Rat Lux Actuating Search Task (LAST) and Effects of Sleep Deprivation on Task Reversal Performance

The article of record as published may be found at�https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4124170Sleep deprivation (SD) causes significant deficits in multiple aspects of cognition, including sustained attention and working memory. Investigating the neural processes underpinning these cognitive losses has proven challenging due to the confounds of current animal tasks; many employ appetitive or aversive stimuli to motivate behavior, while others lack task complexity that translates to human studies of executive function. We established the Lux Actuating Search Task (LAST) to circumvent these issues. The LAST is performed in a circular, open-field arena that requires rats to find an unmarked, quasi-randomly positioned target. Constant low-level floor vibrations motivate ambulation, while light intensity (determined by the rodent's proximity to the target destination) provides continuous visual feedback. The task has two paradigms that differ based on the relationship between the light intensity and target proximity: the Low Lux Target (LLT) paradigm and the High Lux Target paradigm (HLT). In this study, on days 1 to 6, the rats completed nine trials per day on one of the two paradigms. On day 7, the rats were either sleep deprived by gentle handling or were left undisturbed before undertaking the opposite (reversal) paradigm on days 7 to 9. Our results showed that SD significantly impeded the ability of Long Evans rats to learn the reversal paradigm, as indicated by increased times to target and increased failure percentages compared to rats whose sleep was undisturbed. Rats also showed reduced learning with the HLT paradigm, as the initial task or as the reversal task, likely due to the rodents' photophobia limiting their motivation to navigate toward a bright light, which is required to succeed

A case of acute myeloid leukemia with promyelocytic features characterized by expression of a novel RARG-CPSF6 fusion

Key Points Novel RARG-CPSF6 fusion in an AML case with promyelocytic features and no evidence of PML-RARA or X-RARA fusion. Gene fusions involving RARG can initiate AML with promyelocytic morphological features.</jats:p

Wide-field Multi-object Spectroscopy to Enhance Dark Energy Science from LSST

LSST will open new vistas for cosmology in the next decade, but it cannot reach its full potential without data from other telescopes. Cosmological constraints can be greatly enhanced using wide-field ($>20$ deg$^2$ total survey area), highly-multiplexed optical and near-infrared multi-object spectroscopy (MOS) on 4-15m telescopes. This could come in the form of suitably-designed large surveys and/or community access to add new targets to existing projects. First, photometric redshifts can be calibrated with high precision using cross-correlations of photometric samples against spectroscopic samples at $0 < z < 3$ that span thousands of sq. deg. Cross-correlations of faint LSST objects and lensing maps with these spectroscopic samples can also improve weak lensing cosmology by constraining intrinsic alignment systematics, and will also provide new tests of modified gravity theories. Large samples of LSST strong lens systems and supernovae can be studied most efficiently by piggybacking on spectroscopic surveys covering as much of the LSST extragalactic footprint as possible (up to $\sim20,000$ square degrees). Finally, redshifts can be measured efficiently for a high fraction of the supernovae in the LSST Deep Drilling Fields (DDFs) by targeting their hosts with wide-field spectrographs. Targeting distant galaxies, supernovae, and strong lens systems over wide areas in extended surveys with (e.g.) DESI or MSE in the northern portion of the LSST footprint or 4MOST in the south could realize many of these gains; DESI, 4MOST, Subaru/PFS, or MSE would all be well-suited for DDF surveys. The most efficient solution would be a new wide-field, highly-multiplexed spectroscopic instrument in the southern hemisphere with $>6$m aperture. In two companion white papers we present gains from deep, small-area MOS and from single-target imaging and spectroscopy.Comment: Submitted to the call for Astro2020 science white papers; tables with estimates of telescope time needed for a supernova host survey can be seen at http://d-scholarship.pitt.edu/id/eprint/3604

Deep Multi-object Spectroscopy to Enhance Dark Energy Science from LSST

Community access to deep (i ~ 25), highly-multiplexed optical and near-infrared multi-object spectroscopy (MOS) on 8-40m telescopes would greatly improve measurements of cosmological parameters from LSST. The largest gain would come from improvements to LSST photometric redshifts, which are employed directly or indirectly for every major LSST cosmological probe; deep spectroscopic datasets will enable reduced uncertainties in the redshifts of individual objects via optimized training. Such spectroscopy will also determine the relationship of galaxy SEDs to their environments, key observables for studies of galaxy evolution. The resulting data will also constrain the impact of blending on photo-z's. Focused spectroscopic campaigns can also improve weak lensing cosmology by constraining the intrinsic alignments between the orientations of galaxies. Galaxy cluster studies can be enhanced by measuring motions of galaxies in and around clusters and by testing photo-z performance in regions of high density. Photometric redshift and intrinsic alignment studies are best-suited to instruments on large-aperture telescopes with wider fields of view (e.g., Subaru/PFS, MSE, or GMT/MANIFEST) but cluster investigations can be pursued with smaller-field instruments (e.g., Gemini/GMOS, Keck/DEIMOS, or TMT/WFOS), so deep MOS work can be distributed amongst a variety of telescopes. However, community access to large amounts of nights for surveys will still be needed to accomplish this work. In two companion white papers we present gains from shallower, wide-area MOS and from single-target imaging and spectroscopy.Comment: Science white paper submitted to the Astro2020 decadal survey. A table of time requirements is available at http://d-scholarship.pitt.edu/36036