Impact of Size and Delay on Neural Activity in the Rat Limbic Corticostriatal System

A number of factors influence an animal’s economic decisions. Two most commonly studied are the magnitude of and delay to reward. To investigate how these factors are represented in the firing rates of single neurons, we devised a behavioral task that independently manipulated the expected delay to and size of reward. Rats perceived the differently delayed and sized rewards as having different values and were more motivated under short delay and big-reward conditions than under long delay and small reward conditions as measured by percent choice, accuracy, and reaction time. Since the creation of this task, we have recorded from several different brain areas including, orbitofrontal cortex, striatum, amygdala, substantia nigra pars reticulata, and midbrain dopamine neurons. Here, we review and compare those data with a substantial focus on those areas that have been shown to be critical for performance on classic time discounting procedures and provide a potential mechanism by which they might interact when animals are deciding between differently delayed rewards. We found that most brain areas in the cortico-limbic circuit encode both the magnitude and delay to reward delivery in one form or another, but only a few encode them together at the single neuron level

<i>Spitzer</i> Microlensing Parallax Reveals Two Isolated Stars in the Galactic Bulge

We report the mass and distance measurements of two single-lens events from the 2017 $\textit {Spitzer}$ microlensing campaign. The ground-based observations yield the detection of finite-source effects, and the microlens parallaxes are derived from the joint analysis of ground-based observations and $\textit {Spitzer}$ observations. We find that the lens of OGLE-2017-BLG-1254 is a 0.60 ± 0.03 M ⊙ star with D LS = 0.53 ± 0.11 kpc, where D LS is the distance between the lens and the source. The second event, OGLE-2017-BLG-1161, is subject to the known satellite parallax degeneracy, and thus is either a ${0.51}_{-0.10}^{+0.12}\,{M}_{\odot }$ star with D LS = 0.40 ± 0.12 kpc or a ${0.38}_{-0.12}^{+0.13}\,{M}_{\odot }$ star with D LS = 0.53 ± 0.19 kpc. Both of the lenses are therefore isolated stars in the Galactic bulge. By comparing the mass and distance distributions of the eight published $\textit {Spitzer}$ finite-source events with the expectations from a Galactic model, we find that the $\textit {Spitzer}$ sample is in agreement with the probability of finite-source effects occurring in single-lens events

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Spitzer Microlensing Parallax for OGLE-2017-BLG-0896 Reveals a Counter-rotating Low-mass Brown Dwarf

The kinematics of isolated brown dwarfs in the Galaxy, beyond the solar neighborhood, is virtually unknown. Microlensing has the potential to probe this hidden population, as it can measure both the mass and five of the six phase-space coordinates (all except the radial velocity) even of a dark isolated lens. However, the measurements of both the microlens-parallax and finite-source effects are needed in order to recover the full information. Here, we combine the Spitzer satellite parallax measurement with the ground-based light curve, which exhibits strong finite-source effects, of event OGLE-2017-BLG-0896. We find two degenerate solutions for the lens (due to the known satellite-parallax degeneracy), which are consistent with each other except for their proper motion. The lens is an isolated brown dwarf with a mass of either 18 ± 1 M J or 20 ± 1 M J . This is the lowest isolated-object mass measurement to date, only ~45% more massive than the theoretical deuterium-fusion boundary at solar metallicity, which is the common definition of a free-floating planet. The brown dwarf is located at either 3.9 ± 0.1 kpc or 4.1 ± 0.1 kpc toward the Galactic bulge, but with proper motion in the opposite direction of disk stars, with one solution suggesting it is moving within the Galactic plane. While it is possibly a halo brown dwarf, it might also represent a different, unknown population

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Performance and heterosis in farmed and wild Chinook salmon (Oncorhynchus tshawytscha) hybrid and purebred crosses

This study examined traits in Chinook salmon hybrid and purebred crosses for performance differences between wild and farmed fish, and evidence of heterosis. Chinook salmon from two sources were used as parental stock fish from a commercial salmon farm and fish from a natural population (with an active enhancement program). The study population consisted of farmed and wild purebred families and their reciprocal hybrids. Twelve traits were measured in five areas of performance (survival, saltwater growth, saltwater tolerance, stress response and recovery, and fecundity). Significant cross type effects were found for 5 of the 12 traits, and, generally, the wild purebreds performed best. Notable heterosis (i.e., \u3e1% of the mid-parent values) was demonstrated for nine of the performance traits, with four of those being favourable heterosis. However, none of the heterosis exceeded the performance of the best parental lineage. Individual reciprocal crosses showed greater heterosis, but again generally not useful for breeding programs. The lack of favourable heterosis coupled with its generally small effect when present indicates that crossbreeding for hybrid vigour is of limited utility in Chinook salmon culture. The introduction of novel (wild) genetic material into the farmed population did, however, result in considerable performance improvement in growth-related traits, although a loss in disease survival performance was also realized. The observed differences in performance between the purebred wild and farmed families is likely primarily due to additive genetic variation, since the reciprocal hybrid values were generally not significantly different from the mid-parent value. Although our data do not support the use of crossbreeding as a method for exploiting hybrid vigour in Chinook salmon, we do show that significant improvement in performance may result from the inclusion of ‘‘wild’’ gametes in a breeding program; however, some performance losses may also result

Rapid evolution of egg size in captive salmon

Captive breeding and release programs, widely used to supplement popu-lations of declining species, minimize juvenile mortality to achieve rapid population growth. However, raising animals in benign environments may promote traits that are adaptive in captivity but maladaptive in nature. In chinook salmon, hatchery rearing relaxes natural selection favoring large eggs, allowing fecundity selection to drive exceptionally rapid evolution of small eggs. Trends toward small eggs are also evident in natural populations heavily supplemented by hatcheries, but not in minimally supplemented populations. Unintentional selection in captivity can lead to rapid changes in critical life-history traits that may reduce the success of supplementation or reintroduction programs. The use of captive breeding programs is widespread, and increased use of such pro-grams for species preservation has been rec-ommended (1, 2). However, there is consid