Dimensionality reduction beyond neural subspaces with slice tensor component analysis.

Recent work has argued that large-scale neural recordings are often well described by patterns of coactivation across neurons. Yet the view that neural variability is constrained to a fixed, low-dimensional subspace may overlook higher-dimensional structure, including stereotyped neural sequences or slowly evolving latent spaces. Here we argue that task-relevant variability in neural data can also cofluctuate over trials or time, defining distinct 'covariability classes' that may co-occur within the same dataset. To demix these covariability classes, we develop sliceTCA (slice tensor component analysis), a new unsupervised dimensionality reduction method for neural data tensors. In three example datasets, including motor cortical activity during a classic reaching task in primates and recent multiregion recordings in mice, we show that sliceTCA can capture more task-relevant structure in neural data using fewer components than traditional methods. Overall, our theoretical framework extends the classic view of low-dimensional population activity by incorporating additional classes of latent variables capturing higher-dimensional structure.

Novel retinoid ester in combination with salicylic acid for the treatment of acne.

BACKGROUND: Retinoids (RC), alpha-hydroxy acids (AHA), and salicylic acid (BHA) treat acne through differing mechanisms of action. It is theorized that optimal improvement can be achieved by combining the RC-induced normalization of cellular differentiation, AHA-induced exfoliation in hydrophilic areas, and BHA-induced exfoliation in lipophilic areas. AHA and RC have been combined in a bioengineered molecule (AHA retinoid conjugate, or AHA-RC) delivering both lactic acid (AHA) and RC in a manner reducing retinoid-associated irritation. OBJECTIVES: To evaluate efficacy and tolerability of a twice-daily, three-product skincare regimen using AHA-RC in combination with BHA for patients with acne. METHODS: A total of 27 women (age range 20-58 years, mean 37.81 ± 10.04 years) with mild-to-moderate acne used a 3-product regimen consisting of a twice-daily cleanser and topical serum (0.1% AHA-RC, 2% salicylic acid, and 10.4% l-lactic acid), with broad-spectrum SPF 50+ sunscreen as needed, over an 8-week period. Counts were made at baseline, week 4, and week 8 of total inflammatory (papules, pustules) and noninflammatory (open comedones, closed comedones) lesions. Dryness, stinging, and other secondary endpoints were rated on a 0-5 scale. RESULTS: Statistically significant reduction in inflammatory and noninflammatory lesion counts (P = 0.006 and P = 0.015, respectively) was noted at 4 weeks. Improvement continued into week 8 with highly significant (P < 0.001) reductions in both lesion counts. CONCLUSIONS: The topical combination of lactic acid, SA, and AHA-RC produced acne improvement after 4 weeks with continuing cumulative improvement at 8 weeks. AHA-RC represents a new molecule combining several mechanisms of action to achieve acne improvement.

The Tolerability and Efficacy of a Three-product Anti-aging Treatment Regimen in Subjects with Moderate-to-severe Photodamage.

Retinoids and alpha hydroxy acids differ in mechanism of action for treatment of photodamage, but concurrent use may produce a synergistic effect by combining retinoid-induced normalization of cellular differentiation with alpha hydroxy acid-induced exfoliation (in hydrophilic areas) and enhanced dermal and epidermal hydration. A recent bioengineered molecule, ethyl lactyl retinoate (alpha hydroxy acid retinoid conjugate), is the first to deliver alpha hydroxy acids and retinoids together in a hydrolysis-based time-released fashion. This could improve efficacy while minimizing irritation commonly associated with retinoid use. An eight-week clinical study was conducted to examine the efficacy and tolerability of this formulation; 25 women aged 54.1 ±8.9 years (mean ± SD) with moderate-to-severe photodamage (as determined by physician investigators using the Glogau Wrinkle Scale) employed a twice-daily regimen of cleanser (7.8% 1-lactic acid, 2% salicylic acid) and anti-aging serum (0.1% alpha hydroxy acids-retinoids, 6.5% 1-lactic acid) with concurrent use of sun protection factor 50+ sunscreen as needed. Longitudinal analysis of study data revealed statistically significant improvement in photodamage, dryness/flaking, dyschromia, and global appearance at eight weeks. All study products were well-tolerated throughout. Investigators concluded that the alpha hydroxy acid retinoid conjugate is a safe and effective topical therapy for moderate-to-severe photodamage, warranting further study, (clinicaltrials.gov, NCT02422836, https://clinicaltrials.gov/ct2/show/NCT02422836?term=NCT02422836).