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Our results suggest that a major global function of glycinergic and GABAergic interneurons in the mammalian retina is to provide the flexibility for adjusting the size and location of GCs’ RF centers. The apparent shifts of GC RF centers suggest that the synergistic addition by GlyACs and the surround inhibition by GABAergic interneurons are not spatially symmetrical within GC RFs. The current study explored the effects of contrast adaptation on the accommodation response (AR), using low- and high-pass filtered video clips as stimuli. Ten young myopic (mean ± standard deviation -2.91 ± 1.36D) and 10 near emmetropic subjects (-0.19 ± 0.14D) participated in the study. The AR was monitored under monocular viewing conditions using an eccentric infrared photorefractor. A 2-stage procedure was used (1) the minimum spatial frequency content necessary to produce a proper individual AR; and (2) the AR was compared before and after adaptation to low-pass (s = -0.5), control (s = 0) and high-pass (s = +0.5) filtered videos. We found that (1) the average threshold Sinc-blur of both myopes and emmetropes necessary to evoke accommodation was (mean ± standard deviation) λ = 7.40 ± 4.05 cpd. Myopes required a higher Sinc blur (average, 10.00 ± 4.05 cpd) compared to emmetropes (average, 4.80 ± 1.60 cpd). (2) Adaptation to low-pass filtered videos increased the AR by 0.41 ± 0.33D in the myopic group and reduced it in the emmetropic group by 0.31 ± 0.25D. Adaptation to high pass-filtered videos induced similar changes in both refractive groups (an increase of 0.41 ± 0.40D and 0.46 ± 0.29D for myopes and emmetropes, respectively). Our measurements show that the human AR can be modified by spatial frequency selective contrast adaptation although these were short-term effects. The perhaps most striking finding was that adaptation to low pass filtered videos had opposite effects on the AR in emmetropes and myopes. It remains to be studied whether these differences were a consequence of myopia or a contributing factor in myopia development. To create neural representations of external stimuli, the brain performs a number of processing steps that transform its inputs. For fundamental attributes, such as stimulus contrast, this involves one or more nonlinearities that are believed to optimise the neural code to represent features of the natural environment. Here we ask if the same is also true of more complex stimulus dimensions, such as emotional facial expression. We report the results of three experiments combining morphed facial stimuli with electrophysiological and psychophysical methods to measure the function mapping emotional expression intensity to internal response. The results converge on a nonlinearity that accelerates over weak expressions, and then becomes shallower for stronger expressions, similar to the situation for lower level stimulus properties. We further demonstrate that the nonlinearity is not attributable to the morphing procedure used in stimulus generation. BACKGROUND Ivabradine is guideline-recommended to reduce heart failure (HF) hospitalization in patients with stable chronic HF with reduced ejection fraction (EF). Ivabradine initiation following acute HF has had limited evaluation, and there are few randomized data in US patients. The PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) study was conducted to address predischarge ivabradine initiation in stabilized acute HF patients. METHODS PRIME-HF was an investigator-initiated, randomized, open-label study of predischarge initiation of ivabradine versus usual care. Eligible patients were hospitalized for acute HF but stabilized, with EF ≤35%, on maximally tolerated β-blocker and in sinus rhythm with heart rate ≥70 beats/min. Ivabradine was acquired per routine care. The primary end point was the proportion of patients on ivabradine at 180 days. Additional end points included heart rate change, patient-reported outcomes, β-blocker use/dose, and safety events (symptomatic bradycardia and hypotension). RESULTS Overall, 104 patients (36% women, 64% African American) were randomized, and the study was terminated early because of funding limitations. At 180 days, 21 of 52 (40.4%) of patients randomized to predischarge initiation were treated with ivabradine compared with 6 of 52 (11.5%) randomized to usual care (odds ratio 5.19, 95% CI 1.88-14.33, P = .002). The predischarge initiation group experienced greater reduction in heart rate through 180 days (mean -10.0 beats/min, 95% CI -15.7 to -4.3 vs 0.7 beats/min, 95% CI -5.4 to 6.7, P = .011). Patient-reported outcomes, β-blocker use/dose, and safety events were similar (all P > .05). selleck kinase inhibitor CONCLUSIONS Ivabradine initiation prior to discharge among stabilized HF patients increased ivabradine use at 180 days and lowered heart rates without reducing β-blockers or increasing adverse events. As the trial did not achieve the planned enrollment, additional studies are needed. The neuropeptide corticotropin-releasing factor (CRF) is critical in neural circuit function and behavior, particularly in the context of stress, anxiety, and addiction. Despite a wealth of preclinical evidence for the efficacy of CRF receptor 1 antagonists in reducing behavioral pathology associated with alcohol exposure, several clinical trials have had disappointing outcomes, possibly due to an underappreciation of the role of biological variables. Although he National Institutes of Health (NIH) now mandate the inclusion of sex as a biological variable in all clinical and preclinical research, the current state of knowledge in this area is based almost entirely on evidence from male subjects. Additionally, the influence of biological variables other than sex has received even less attention in the context of neuropeptide signaling. Age (particularly adolescent development) and housing conditions have been shown to affect CRF signaling and voluntary alcohol intake, and the interaction between these biological variables is particularly relevant to the role of the CRF system in the vulnerability or resilience to the development of alcohol use disorder (AUD). Going forward, it will be important to include careful consideration of biological variables in experimental design, reporting, and interpretation. As new research uncovers conditions in which sex, age, and environment play major roles in physiological and/or pathological processes, our understanding of the complex interaction between relevant biological variables and critical signaling pathways like the CRF system in the cellular and behavioral consequences of alcohol exposure will continue to expand ultimately improving the ability of preclinical research to translate to the clinic.