HRV has several advantages compared to other measures of autonomic reactivity in studies investigating physiological response to nociceptive stimulation. Future studies should focus on comparisons between different methods of pain induction, interindividual variability in pain sensitivity by baseline autonomic activity, and the implications of both on the use of HRV within routine clinical evaluations.

Purpose Combination PD-1/CTLA-4 blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAFV600 mutant metastatic melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy. Methods In a phase III trial, patients with treatment-naïve BRAFV600-mutant metastatic melanoma were randomized to receive either combination nivolumab/ipilimumab (Arm A) or dabrafenib/trametinib (Arm B) in Step 1, and at disease progression were enrolled in Step 2 receiving the alternate therapy, dabrafenib/trametinib (Arm C) or nivolumab/ipilimumab (Arm D). The primary endpoint was 2-year overall survival. Secondary endpoints were 3-year overall survival, objective response rate, response duration, progression-free survival, crossover feasibility and safety. Results 265 patients were enrolled with 73 going onto Step 2 (27 Arm C, 46 Arm D). The study was stopped early by the independent DSMC due to a clinically significant endpoint being achieved. The 2-year overall survival for those starting on Arm A was 71.8% (62.5, 79.1%) and Arm B 51.5% (41.7, 60.4%) (log-rank p=0.010). Step 1 progression-free survival favored Arm A (p=0.054). Objective response rates were: Arm A:46.0%; Arm B:43.0%; Arm C:47.8%; Arm D:29.6%. Median duration of response was not reached for Arm A and 12.7 months for Arm B (p<0.001). Crossover occurred in 52% of patients with documented disease progression. Grade >3 toxicities occurred with similar frequency between arms and regimen toxicity profiles were as anticipated. Conclusion Combination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.

Despite a wealth of evidence for the involvement of the autonomic nervous system (ANS) in health and disease and the ability of music to affect ANS activity, few studies have systematically explored the therapeutic effects of music on ANS dysfunction. Furthermore, when ANS activity is quantified and analyzed, it is usually from a point of convenience rather than from an understanding of its physiological basis. After a review of the experimental and therapeutic literatures exploring music and the ANS, a "Neurovisceral Integration" perspective on the interplay between the central and autonomic nervous systems is introduced, and the associated implications for physiological, emotional, and cognitive health are explored. The construct of heart rate variability is discussed both as an example of this complex interplay and as a useful metric for exploring the sometimes subtle effect of music on autonomic response. Suggestions for future investigations using musical interventions are offered based on this integrative account.

Humans uniquely appreciate aesthetics, experiencing pleasurable responses to complex stimuli that confer no clear intrinsic value for survival. However, substantial variability exists in the frequency and specificity of aesthetic responses. While pleasure from aesthetics is attributed to the neural circuitry for reward, what accounts for individual differences in aesthetic reward sensitivity remains unclear. Using a combination of survey data, behavioral and psychophysiological measures and diffusion tensor imaging, we found that white matter connectivity between sensory processing areas in the superior temporal gyrus and emotional and social processing areas in the insula and medial prefrontal cortex explains individual differences in reward sensitivity to music. Our findings provide the first evidence for a neural basis of individual differences in sensory access to the reward system, and suggest that social-emotional communication through the auditory channel may offer an evolutionary basis for music making as an aesthetically rewarding function in humans.

BackgroundA well-established connection exists between increased gait variability and greater fall likelihood in Parkinson’s disease (PD); however, a portable, validated means of quantifying gait variability (and testing the efficacy of any intervention) remains lacking. Furthermore, although rhythmic auditory cueing continues to receive attention as a promising gait therapy for PD, its widespread delivery remains bottlenecked. The present paper describes a smartphone-based mobile application (“SmartMOVE”) to address both needs.MethodsThe accuracy of smartphone-based gait analysis (utilizing the smartphone’s built-in tri-axial accelerometer and gyroscope to calculate successive step times and step lengths) was validated against two heel contact–based measurement devices: heel-mounted footswitch sensors (to capture step times) and an instrumented pressure sensor mat (to capture step lengths). 12 PD patients and 12 age-matched healthy controls walked along a 26-m path during self-paced and metronome-cued conditions, with all three devices recording simultaneously.ResultsFour outcome measures of gait and gait variability were calculated. Mixed-factorial analysis of variance revealed several instances in which between-group differences (e.g., increased gait variability in PD patients relative to healthy controls) yielded medium-to-large effect sizes (eta-squared values), and cueing-mediated changes (e.g., decreased gait variability when PD patients walked with auditory cues) yielded small-to-medium effect sizes—while at the same time, device-related measurement error yielded small-to-negligible effect sizes.ConclusionThese findings highlight specific opportunities for smartphone-based gait analysis to serve as an alternative to conventional gait analysis methods (e.g., footswitch systems or sensor-embedded walkways), particularly when those methods are cost-prohibitive, cumbersome, or inconvenient.

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Previous research indicates that temporal accents (TAs; accents due to time changes) play a strong role in meter perception, but evidence favoring a role for melodic accents (MAs; accents due to pitch changes) is mixed. The authors claim that this mixed support for MAs is the result of a failure to control for accent salience and addressed this hypothesis in Experiment 1. Listeners rated the metrical clarity of 13-tone melodies in which the magnitude and pattern of MAs and TAs were varied. Results showed that metrical clarity increased with both MA and TA magnitude. In Experiment 2, listeners were asked to rate metrical clarity in melodies with combinations of MA and TA patterns to allow the authors to ascertain whether these two accent types combined additively or interactively in meter perception. With respect to the additive or interactive debate, the findings highlighted the importance of (a) accent salience, (b) scoring methods, and (c) conceptual versus statistical interpretations of data. Implications for dynamic attending and neuropsychological investigations are discussed.

ObjectiveTranslations of the Diabetes Prevention Program (DPP) have proliferated in recent years, with increasing expansion to digital formats. Although these DPP translations have consistently shown favorable clinical outcomes, long-term data for digital formats are limited. This study’s objective was to examine clinical outcomes up to 3 years post-baseline and the relationship between program engagement and clinical outcomes in a digital DPP.Research design and methodsIn a single-arm, non-randomized trial, 220 patients previously diagnosed with prediabetes were enrolled in the Omada Health Program, a commercially available, 16-week DPP-based weight loss intervention followed by an ongoing weight maintenance intervention. Changes in body weight and A1c were assessed annually. Relationships between program engagement during the first year and clinical outcomes across 3 years were examined.ResultsParticipants were socioeconomically diverse (62% women, 50.2% non-Hispanic white, 51.7% college educated or higher). From baseline to 3 years, those participants who completed four or more lessons and nine or more lessons achieved significant sustained weight loss (–3.0% and –2.9%, respectively) and an absolute reduction in A1c (–0.31 and –0.33, respectively) with an average remission from the prediabetes range to the normal glycemic range. Factor analysis of engagement metrics during the first year revealed two underlying dimensions, one comprising lesson completion and health behavior tracking consistency, and the other comprising website logins and group participation. When these two factors were used to predict weight loss, only the logins and group participation factor was a significant predictor of weight loss at 16 weeks and 1 year.ConclusionsThis study demonstrates significant long-term reductions in body weight and A1c in a digital DPP and identifies patterns of program engagement that predict weight loss.