Learning, Mood, and Music: Depression, anxiety, and stress reflect processing biases in positive and negative chord sequences

Cognitive biases in information processing of valenced stimuli are a major contributor to the phenomenology of mood disorders. However, current screening tools for mood disorders rely on self-report questionnaires, which include uncomfortably invasive questions and are confounded by socially desirable responding. Taken together, assessing information processing biases may be a promising proxy to screen non-invasively for mood disorders. Here, we report data of 60 participants that performed a continuous statistical learning task in which respondents were asked to predict the next event in a sequence of musical chords. An underlying transitional probability matrix governed the chord sequences. Each participant performed both a positive- and negative-valence block of this task, where blocks differed in the precise musical chords used. A pilot experiment established that the sequences from both blocks evoked their intended perceived valence. Furthermore, cognitive assessment (Raven’s advanced matrices) as well as mood scores (DASS-21) were collected. Bayesian mixed effects models revealed that participants were able to extract the underlying transitional probabilities and that higher cognitive ability predicted higher performance. Furthermore, there was strong evidence that the depression, anxiety, and stress subscales all predicted learning trajectories, and interacted with stimulus valence. Thus, the present results show that information processing differences in a musical context are consistent with the phenomenology of mood disorders. The present study is one step towards a non-invasive musical tool to screen for mood disorders

Contributions of pitch contour, tonality, rhythm, and meter to melodic similarity

The identity of a melody resides in its sequence of pitches and durations, both of which exhibit surface details as well as structural properties. In this study, pitch contour (pattern of ups and downs) served as pitch surface information, and tonality (musical key) as pitch structure; in the temporal dimension, surface information was the ordinal duration ratios of adjacent notes (rhythm), and meter (beat, or pulse) comprised the structure. Factorially manipulating the preservation or alteration of all of these forms of information in 17 novel melodies (typifying Western music) enabled measuring their effect on perceived melodic similarity. In Experiment 1, 34 participants (varied musical training) rated the perceived similarity of melody pairs transposed to new starting pitches. Rhythm was the largest contributor to perceived similarity, then contour, meter, and tonality. Experiment 2 used the same melodies but varied the tempo within a pair, and added a prefix of 3 chords, which oriented the listener to the starting pitch and tempo before the melody began. Now contour was the strongest influence on similarity ratings, followed by tonality, and then rhythm; meter was not significant. Overall, surface features influenced perceived similarity more than structural, but both had observable effects. The primary theoretical advances in melodic similarity research are that (a) the relative emphasis on pitch and temporal factors is flexible; (b) pitch and time functioned independently when factorially manipulated, regardless of which dimension is more influential; and (c) interactions between surface and structural information were unreliable and never occurred between dimensions

Pitch structure, but not selective attention, affects accent weightings in metrical grouping

Among other cues, pitch and temporal accents contribute to grouping in musical sequences. However, exactly how they combine remains unclear, possibly because of the role of structural organization. In 3 experiments, participants rated the perceived metrical grouping of sequences that either adhered to the rules of tonal Western musical pitch structure (musical key) or did not (atonal). The tonal status of sequences did not provide any grouping cues and was irrelevant to the task. Experiment 1 established equally strong levels of pitch leap accents and duration accents in baseline conditions, which were then recombined in subsequent experiments. Neither accent type was stronger or weaker for tonal and atonal contexts. In Experiment 2, pitch leap accents dominated over duration accents, but the extent of this advantage was greater when sequences were tonal. Experiment 3 ruled out an attentional origin of this effect by replicating this finding while explicitly manipulating attention to pitch or duration accents between participant groups. Overall, the presence of tonal pitch structure made the dimension of pitch more salient at the expense of time. These findings support a dimensional salience framework in which the presence of organizational structure prioritizes the processing of the more structured dimension regardless of task relevance, independent from psychophysical difficulty, and impervious to attentional allocation

Operational management of trunk main discolouration risk

Despite significant on-going investment, water companies continue to receive an unacceptable number of discolouration related customer contacts. In this paper, data from intensive distribution system turbidity monitoring and cluster analysis of discolouration customer contacts indicate that a significant proportion of these contacts are due to material mobilising from the trunk main system, and operational flow increases are shown to have a higher discolouration risk than burst incidents. A trunk main discolouration incident highlighting this risk is discussed, demonstrating the need for pro-active trunk main risk assessments. To identify the source of the material event flow rates were modelled using the PODDS (prediction of discolouration in distribution systems) discolouration model. Best practice pro-active management is demonstrated in a case study where the PODDS model is used to implement managed incremental flow changes on a main with known discolouration risk with no discolouration impact to customers and significant cost savings

Observational constraints on the neutron star mass distribution

Radio observations of neutron star binary pulsar systems have constrained strongly the masses of eight neutron stars. Assuming neutron star masses are uniformly distributed between lower and upper bounds $m_l$ and $m_u$, the observations determine with 95\% confidence that $1.01 < m_l/\text{M}_\odot < 1.34$ and $1.43 < m_u/\text{M}_\odot < 1.64$. These limits give observational support to neutron star formation scenarios that suggest that masses should fall predominantly in the range $1.3<m/\text{M}_\odot<1.6$, and will also be important in the interpretation of binary inspiral observations by the Laser Interferometer Gravitational-wave Observatory.Comment: Postscript, 4 pages, NU-GR-

Population Modeling Highlights Drug Disposition Differences Between Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate in the Blood and Semen

Understanding antiretroviral disposition in the male genital tract, a distinct viral compartment, can provide insight for the eradication of HIV. Population pharmacokinetic modeling was conducted to investigate the disposition of tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and emtricitabine and their metabolites in blood and semen. Blood plasma and seminal plasma (SP) concentrations of tenofovir and emtricitabine were measured, as were tenofovir-diphosphate and emtricitabine-triphosphate concentrations in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells. Sequential compartmental modeling described drug disposition in blood and semen. Our modeling suggests slower elimination of apparent tenofovir-diphosphate PBMC and faster elimination of tenofovir SP after administration of TAF compared with TDF, likely reflecting flip-flop kinetics. Additionally, TAF metabolism to tenofovir appeared slower in semen compared with blood; however, SP elimination of TAF-derived tenofovir appeared faster than its blood plasma elimination. These findings provide valuable insight for further mechanistic study of cellular entry and drug metabolism in the male genital tract

Differential Extracellular, but Similar Intracellular, Disposition of two Tenofovir Formulations in the Male Genital Tract

Background: The male genital tract (MGT) is a viral sanctuary and likely HIV reservoir; understanding MGT pharmacokinet-ics (PK) of antiretrovirals (ARVs) used for curative strategies is critical to eradication and cure. Tenofovir alafenamide (TAF) is a tenofovir (TFV) formulation designed to maximize efficacy/minimize toxicity with unknown MGT PK. Methods: HIV-positive and HIV-negative men receiving TFV-based regimens provided six paired blood plasma (BP) and semen samples. Extracellular (TFV, TAF, emtricitabine [FTC]) drug concentrations in BP and seminal plasma (SP), and intracellular metabolite (IM) and endogenous nucleotide (EN) concentrations were measured in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs). Exposure ratios for SP:BP, SMC:PBMC and IM:EN were calculated from PK parameters generated by noncompartmental analysis. HIV viral load was measured in BP and SP. Results: Sixteen HIV-positive (n=8, TDF/FTC; n=8, TAF/FTC) and eight HIV-negative (TDF/FTC) men provided samples. Median TFV SP:BP ratios differed between TDF and TAF (1.5 versus 7.4), due to lower TFV BP concentrations with TAF coupled with TFV SP concentrations similar to TDF. FTC SP:BP ratios were approximately 3. SMC concentrations of IMs and ENs were a fraction of PBMC concentrations (1–22%), though IM:EN ratios exceed a suggested protective threshold. Conclusions: TAF SP PK was unexpected. IM SMC concentrations were low relative to PBMC, as were EN concentrations, suggesting differences in cell phenotype and lineage in the MGT; these differences in phenotype and pharmacology may have an impact on selecting and dosing ARVs used in cure strategies

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity