Reducing Reparameterization Gradient Variance

Optimization with noisy gradients has become ubiquitous in statistics and machine learning. Reparameterization gradients, or gradient estimates computed via the "reparameterization trick," represent a class of noisy gradients often used in Monte Carlo variational inference (MCVI). However, when these gradient estimators are too noisy, the optimization procedure can be slow or fail to converge. One way to reduce noise is to use more samples for the gradient estimate, but this can be computationally expensive. Instead, we view the noisy gradient as a random variable, and form an inexpensive approximation of the generating procedure for the gradient sample. This approximation has high correlation with the noisy gradient by construction, making it a useful control variate for variance reduction. We demonstrate our approach on non-conjugate multi-level hierarchical models and a Bayesian neural net where we observed gradient variance reductions of multiple orders of magnitude (20-2,000x)

Intermittent vs Continuous Graded Exercise Test for VO2max in College Soccer Athletes

The purpose of this study was to determine if a 1-min active recovery between stages during a graded exercise test (GXT) would result in a higher stage intensity and maximum oxygen uptake in college soccer athletes. Eleven athletes completed two GXT protocols on separate days. Each GXT consisted of 2-min stages performed at a constant running speed and incremental increases of 2.5% grade. One GXT was performed continuously and the other was intermittent with 1-min active recovery between each stage. Tests were performed to volitional fatigue. Following the each GXT and a 10-min active recovery period, participants performed a verification stage at an intensity greater than the final stage of the GXT. All participants completed a higher intensity stage during the intermittent vs continuous GXT. As a result, VO2max and maximum heart rate (HR) were significantly higher (VO2: 57.7 ± 5.8 vs. 55.5 ± 5.7 ml•kg-1•min-1, HR: 190 ± 6 vs. 187 ± 6 bpm, p \u3c 0.02) during the intermittent GXT. Maximum ventilation and respiratory exchange ratio did not differ between intermittent and continuous protocols. Following the intermittent GXT, nine participants completed the verification stage and obtained VO2 values within the plateau criterion. We conclude that a continuous GXT underestimates VO2max in some athletes and that the intermittent protocol may provide a more accurate measure of VO2max

Repeated Sprint Performance in Male and Female College Athletes Matched for VO2max Relative to Fat Free Mass

The purpose of this study was to examine gender differences in repeated sprint exercise (RSE) performance among male and female athletes matched for VO2max relative to FFM (VO2max FFM). Thirty nine male and female college athletes performed a graded exercise test for VO2max and hydrostatic weighing to determine FFM. From the results, 11 pairs of males and females matched for VO2max FFM (mean ± SD; 58.3 ± 4.3 and 58.9 ± 4.6 ml.kg FFM-1.min-1; men and women, respectively) were identified. On a separate day, matched participants performed a RSE protocol that consisted of five 6-sec cycle sprints with 30-sec recovery periods, followed by 5-min active recovery and a 30-sec all-out sprint. Repeated 6-sec sprint performance did not differ between men and women; both maintained power output (PO) until sprint 4. POFFM (W.kg-1 FFM) did not differ between men and women during the five sprints. During the 30-sec sprint, men achieved a lower peak POFFM than women (11.7 ± 1.5 vs 13.2 ± 1.2); however, the decline in POFFM over 30 sec was greater in women. VO2 (ml.kg FFM-1.min-1) was lower in men during recovery (24.4 ± 3.8 vs 28.7 ± 5.7) and at the beginning (29.2 ± 4.0 vs 34.7 ± 4.9and end (49.4 ± 5.0 vs 52.3 ± 4.0) of the 30-sec sprint. These data indicate that men and women with similar aerobic capacities do not respond differently to short repeated sprints but may differ in their ability to recover and perform sprints of longer duration

Generalized genetic liability to substance use disorders

Lifetime and temporal co-occurrence of substance use disorders (SUDs) is common and compared with individual SUDs is characterized by greater severity, additional psychiatric comorbidities, and worse outcomes. Here, we review evidence for the role of generalized genetic liability to various SUDs. Coaggregation of SUDs has familial contributions, with twin studies suggesting a strong contribution of additive genetic influences undergirding use disorders for a variety of substances (including alcohol, nicotine, cannabis, and others). GWAS have documented similarly large genetic correlations between alcohol, cannabis, and opioid use disorders. Extending these findings, recent studies have identified multiple genomic loci that contribute to common risk for these SUDs and problematic tobacco use, implicating dopaminergic regulatory and neuronal development mechanisms in the pathophysiology of generalized SUD genetic liability, with certain signals demonstrating cross-species and translational validity. Overlap with genetic signals for other externalizing behaviors, while substantial, does not explain the entirety of the generalized genetic signal for SUD. Polygenic scores (PGS) derived from the generalized genetic liability to SUDs outperform PGS for individual SUDs in prediction of serious mental health and medical comorbidities. Going forward, it will be important to further elucidate the etiology of generalized SUD genetic liability by incorporating additional SUDs, evaluating clinical presentation across the lifespan, and increasing the granularity of investigation (e.g., specific transdiagnostic criteria) to ultimately improve the nosology, prevention, and treatment of SUDs

Active Transport of Peptides Across the Intact Human Tympanic Membrane.

We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients