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We provide evidence that the roughness of chords-a psychoacoustic property resulting from unresolved frequency components-is associated with perceived musical stability (operationalized as finishedness) in participants with differing levels and types of exposure to Western or Western-like music. Three groups of participants were tested in a remote cloud forest region of Papua New Guinea (PNG), and two groups in Sydney, Australia (musicians and non-musicians). Unlike prominent prior studies of consonance/dissonance across cultures, we framed the concept of consonance as stability rather than as pleasantness. We find a negative relationship between roughness and musical stability in every group including the PNG community with minimal experience of musical harmony. The effect of roughness is stronger for the Sydney participants, particularly musicians. We find an effect of harmonicity-a psychoacoustic property resulting from chords having a spectral structure resembling a single pitched tone (such as produced by human vowel sounds)-only in the Sydney musician group, which indicates this feature's effect is mediated via a culture-dependent mechanism. In sum, these results underline the importance of both universal and cultural mechanisms in music cognition, and they suggest powerful implications for understanding the origin of pitch structures in Western tonal music as well as on possibilities for new musical forms that align with humans' perceptual and cognitive biases. They also highlight the importance of how consonance/dissonance is operationalized and explained to participants-particularly those with minimal prior exposure to musical harmony.

Many endophytic fungi have the potential to function as saprotrophs when living host tissues senesce and enter the litter pool. The consumption of plant litter by fungi obviously requires moisture but, in the arid, western USA, the native range of Quercus gambelii Nutt., most of the precipitation occurs during the coldest months of the year. Therefore, we hypothesized that the endophytic fungi of Q. gambelii have the potential to function as psychrotolerant saprotrophs, which we defined in this study as an organism capable of significant growth on leaf litter at 5°C. We further hypothesized that a tradeoff exists between growth of endophytic fungi at 5°C and at 17°C such that fungal isolates are either cold- or warm-temperature specialists. Consistent with our first hypothesis, we found that 36 of our 40 isolates consumed leaf litter at 5°C, but there was a surprisingly high degree of variability among isolates in this ability, even among isolates of a given species. Contrary to our second hypothesis, there was no tradeoff between saprotrophic growth at 5°C and saprotrophic growth at 17°C. Indeed, the isolates that grew poorly as saprotrophs at 5°C were generally those that grew poorly as saprotrophs at 17°C. By virtue of being endophytic, endophytic fungi have priority in litter over decomposer fungi that colonize plant tissues only after they enter the litter pool. Moreover, by virtue of being psychrotolerant, some endophytic fungi may function as saprotrophs during the cold months of the year when moisture is temporarily available. Therefore, we suggest that some endophytic fungi of Q. gambelii could play significant ecosystem roles in litter decomposition and nutrient cycling.

Because of disturbance and plant species loss at the local level, many arid ecosystems in the western USA benefit from revegetation. There is a growing interest in improving revegetation success by purposefully inoculating revegetation plants with mutualistic endophytic fungi that increase plant stress tolerance. However, inoculant fungi must compete against fungi that indigenous to the habitat, many of which may not be mutualistic. Our overall goal, therefore, is to learn how to efficiently colonize revegetation plants using endophytic fungal inoculum. The goal will be facilitated by understanding the factors that limit colonization of plants by endophytic fungi, including inoculum dispersal and host compatibility. We analyzed endophytic fungal communities in leaves of Bromus tectorum and Elymus elymoides (Poaceae), Chrysothamnus depressus and Artemisia tridentata (Asteraceae), Alyssum alyssoides (Brassicaceae) and Atriplex canescens (Amaranthaceae), each occurring in each of 18 field plots. We found that dispersal limitation was significant for endophytic fungal communities of Atriplex canescens and Bromus tectorum, accounting for 9 and 17%, respectively, of the variation in endophytic fungal community structure, even though the maximum distance between plots was only 350 m. Plant species identity accounted for 33% of the variation in endophytic fungal community structure. These results indicate that the communities of endophytic fungi assembling in these plant species depend significantly on proximity to inoculum source as well as the identity of the plant species. Therefore, if endophytic fungi are to be used to facilitate revegetation by these plant species, land managers may find it profitable to consider both the proximity of inoculum to revegetation plants and the suitability of the inoculum to targeted host plant species.

This study investigates the role of extrinsic and intrinsic predictors in the perception of affect in mostly unfamiliar musical chords from the Bohlen-Pierce microtonal tuning system. Extrinsic predictors are derived, in part, from long-term statistical regularities in music; for example, the prevalence of a chord in a corpus of music that is relevant to a participant. Conversely, intrinsic predictors make no use of long-term statistical regularities in music; for example, psychoacoustic features inherent in the music, such as roughness. Two types of affect were measured for each chord: pleasantness/unpleasantness and happiness/sadness. We modelled the data with a number of novel and well-established intrinsic predictors, namely roughness, harmonicity, spectral entropy and average pitch height; and a single extrinsic predictor, 12-TET Dissimilarity, which was estimated by the chord's smallest distance to any 12-tone equally tempered chord. Musical sophistication was modelled as a potential moderator of the above predictors. Two experiments were conducted, each using slightly different tunings of the Bohlen-Pierce musical system: a just intonation version and an equal-tempered version. It was found that, across both tunings and across both affective responses, all the tested intrinsic features and 12-TET Dissimilarity have consistent influences in the expected direction. These results contrast with much current music perception research, which tends to assume the dominance of extrinsic over intrinsic predictors. This study highlights the importance of both intrinsic characteristics of the acoustic signal itself, as well as extrinsic factors, such as 12-TET Dissimilarity, on perception of affect in music.

1/f fluctuations have been described in numerous physical and biological processes. This noise structure describes an inverse relationship between the intensity and frequency of events in a time series (for example reflected in power spectra), and is believed to indicate long-range dependence, whereby events at one time point influence events many observations later. 1/f has been identified in rhythmic behaviors, such as music, and is typically attributed to long-range correlations. However short-range dependence in musical performance is a well-established finding and past research has suggested that 1/f can arise from multiple continuing short-range processes. We tested this possibility using simulations and time-series modeling, complemented by traditional analyses using power spectra and detrended fluctuation analysis (as often adopted more recently). Our results show that 1/f-type fluctuations in musical contexts may be explained by short-range models involving multiple time lags, and the temporal ranges in which rhythmic hierarchies are expressed are apt to create these fluctuations through such short-range autocorrelations. We also analyzed gait, heartbeat, and resting-state EEG data, demonstrating the coexistence of multiple short-range processes and 1/f fluctuation in a variety of phenomena. This suggests that 1/f fluctuation might not indicate long-range correlations, and points to its likely origins in musical rhythm and related structures.

Naturally occurring, mixed litter decomposes at unpredictable rates when individual components do not decompose in mixtures as they do individually. Consequently, nutrient, carbon and energy fluxes associated with decomposition may be difficult to predict. However, predictability is improved when we understand the mechanisms responsible for such non-additive decomposition. In this study, we explored mechanisms to explain our previous observation that an approximately 30% increase in oat straw decomposition due to the presence of clover litter is associated with a significant increase in the activity of cellobiohydrolase, an enzyme involved in litter decomposition. We hypothesized that resources limiting decomposer microbe enzyme activity in oat straw can be supplied by clover litter. Amendment of oat straw with water, NH4Cl, glucose, or NH4Cl combined with glucose did not account for the significant, positive effect of clover litter on oat straw decomposition and cellobiohydrolase activity. However, amendment of oat straw with a complete set of mineral nutrients for plant growth did account for the entire effect of clover litter, and the addition of the complete set of mineral nutrients without N accounted for the majority of the clover effect. In our system, therefore, the majority of the positive effect of clover litter on oat straw decomposition and cellobiohydrolase activity was unexpectedly not attributable to the transfer from clover to oat straw of labile N. We found that mineral soil could substitute for the mineral nutrients other than N. This highlights the role of soil as a potential source of limiting resources for microbes decomposing litter. It may also explain why positive, non-additive decomposition has been observed in some previous studies but not in others depending on whether the soil supplied a resource that limited decomposer activity.

Phrasing facilitates the organization of auditory information and is central to speech and music. Not surprisingly, aspects of changing intensity, rhythm, and pitch are key determinants of musical phrases and their boundaries in instrumental note-based music. Different kinds of speech (such as tone- vs. stress-languages) share these features in different proportions and form an instructive comparison. However, little is known about whether or how musical phrasing is perceived in sound-based music, where the basic musical unit from which a piece is created is commonly non-instrumental continuous sounds, rather than instrumental discontinuous notes. This issue forms the target of the present paper. Twenty participants (17 untrained in music) were presented with six stimuli derived from sound-based music, note-based music, and environmental sound. Their task was to indicate each occurrence of a perceived phrase and qualitatively describe key characteristics of the stimulus associated with each phrase response. It was hypothesized that sound-based music does elicit phrase perception, and that this is primarily associated with temporal changes in intensity and timbre, rather than rhythm and pitch. Results supported this hypothesis. Qualitative analysis of participant descriptions showed that for sound-based music, the majority of perceived phrases were associated with intensity or timbral change. For the note-based piano piece, rhythm was the main theme associated with perceived musical phrasing. We modeled the occurrence in time of perceived musical phrases with recurrent event 'hazard' analyses using time-series data representing acoustic predictors associated with intensity, spectral flatness, and rhythmic density. Acoustic intensity and timbre (represented here by spectral flatness) were strong predictors of perceived musical phrasing in sound-based music, and rhythm was only predictive for the piano piece. A further analysis including five additional spectral measures linked to timbre strengthened the models. Overall, results show that even when little of the pitch and rhythm information important for phrasing in note-based music is available, phrasing is still perceived, primarily in response to changes of intensity and timbre. Implications for electroacoustic music composition and music recommender systems are discussed.

Cephalopods are famous for their ability to change color and pattern rapidly for signaling and camouflage. They have keen eyes and remarkable vision, made possible by photoreceptors in their retinas. External to the eyes, photoreceptors also exist in parolfactory vesicles and some light organs, where they function using a rhodopsin protein that is identical to that expressed in the retina. Furthermore, dermal chromatophore organs contain rhodopsin and other components of phototransduction (including retinochrome, a photoisomerase first found in the retina), suggesting that they are photoreceptive. In this study, we used a modified whole-mount immunohistochemical technique to explore rhodopsin and retinochrome expression in a number of tissues and organs in the longfin squid, Doryteuthis pealeii. We found that fin central muscles, hair cells (epithelial primary sensory neurons), arm axial ganglia, and sucker peduncle nerves all express rhodopsin and retinochrome proteins. Our findings indicate that these animals possess an unexpected diversity of extraocular photoreceptors and suggest that extraocular photoreception using visual opsins and visual phototransduction machinery is far more widespread throughout cephalopod tissues than previously recognized.

For listeners familiar with Western twelve-tone equal-tempered (12-TET) music, a novel microtonal tuning system is expected to present additional processing challenges. We aimed to determine whether this was the case, focusing on the extent to which our perceptions can be considered bottom-up (psychoacoustic and primarily perceptual) and top-down (dependent on familiarity and cognitive processing). We elicited both overt response ratings, and covert event-related potentials (ERPs), so as to compare subjective impressions of sounds with the neurophysiological processing of the acoustic signal. We hypothesised that microtonal intervals are perceived differently from 12-TET intervals, and that the responses of musicians (n = 10) and non-musicians (n = 10) are distinct. Two-note chords were presented comprising 12-TET intervals (consonant and dissonant) or microtonal (quarter tone) intervals, and ERP, subjective roughness ratings, and liking ratings were recorded successively. Musical experience mediated the perception of differences between dissonant and microtone intervals, with non-musicians giving similar ratings for each, and musicians preferring dissonant over the less commonly used microtonal intervals, rating them as less rough. ERP response amplitude was greater for consonant intervals than other intervals. Musical experience interacted with interval type, suggesting that musical expertise facilitates the sensory and perceptual discrimination of microtonal intervals from 12-TET intervals, and an increased ability to categorize such intervals. Non-musicians appear to have perceived microtonal intervals as instances of neighbouring 12-TET intervals.

To address the bias occurring in the medical literature associated with selective outcome reporting, in 2005, the International Committee of Medical Journal Editors (ICMJE) introduced mandatory trial registration guidelines and member journals required prospective registration of trials prior to patient enrolment as a condition of publication. No research has examined whether these guidelines are impacting psychiatry publications. Our objectives were to determine the extent to which articles published in psychiatry journals adhering to ICMJE guidelines were correctly prospectively registered, whether there was evidence of selective outcome reporting and changes to participant numbers, and whether there was a relationship between registration status and source of funding.Any clinical trial (as defined by ICMJE) published between 1 January 2009 and 31 July 2013 in the top five psychiatry journals adhering to ICMJE guidelines (The American Journal of Psychiatry, Archives of General Psychiatry/JAMA Psychiatry, Biological Psychiatry, Journal of the American Academy of Child and Adolescent Psychiatry, and The Journal of Clinical Psychiatry) and conducted after July 2005 (or 2007 for two journals) was included. For each identified trial, where possible we extracted trial registration information, changes to POMs between publication and registry to assess selective outcome reporting, changes to participant numbers, and funding type.Out of 3305 articles, 181 studies were identified as clinical trials requiring registration: 21 (11.6%) were deemed unregistered, 61 (33.7%) were retrospectively registered, 37 (20.4%) had unclear POMs either in the article or the registry and 2 (1.1%) were registered in an inaccessible trial registry. Only 60 (33.1%) studies were prospectively registered with clearly defined POMs; 17 of these 60 (28.3%) showed evidence of selective outcome reporting and 16 (26.7%) demonstrated a change in participant numbers of 20% or more; only 26 (14.4%) of the 181 the trials were prospectively registered and did not alter their POMs or the time frames at which they were measured. Prospective registration with no changes in POMs occurred more frequently with pharmaceutical funding.Although standards are in place to improve prospective registration and transparency in clinical trials, less than 15% of psychiatry trials were prospectively registered with no changes in POMs. Most trials were either not prospectively registered, changed POMs or the timeframes at some point after registration or changed participant numbers. Authors, journal editors and reviewers need to further efforts to highlight the value of prospective trial registration.

Immigrant populations in western societies have grown in their size and diversity yet evidence is incomplete for their risks of suicidality and criminal violence. We examined these correlated harmful behaviours in a national cohort.(i) Compare absolute risk between first and second generation immigrants, foreign-born adoptees and native Danes by plotting cumulative incidence curves to onset of early middle age; (ii) estimate sex-specific relative risks for these immigrant type subgroups vs. native Danes; (iii) examine effect modification by higher vs. lower socio-economic status.In a cohort of over two million persons, attempted suicides and violent crimes were investigated using data from multiple interlinked registers. We plotted sex-specific cumulative incidence curves and estimated incidence rate ratios.In the whole study cohort, 1414 people died by suicide, 46,943 attempted suicide, and 51,344 were convicted of committing a violent crime. Among all immigrant subgroups combined, compared with native Danes, relative risk of attempted suicide was greater in female immigrants (incidence rate ratio, 1.59; 95% confidence interval: CI 1.54-1.64) than in male immigrants (1.26; CI 1.20-1.32), and vice versa for relative risk of violent offending in male immigrants (2.36; CI 2.31-2.42) than in female immigrants (1.74; CI 1.62-1.87). Risk for both adverse outcomes was significantly elevated in virtually every gender-specific immigrant type subgroup examined. Violent crime risk was markedly raised in first generation immigrant males and in the Danish born male children of two immigrant parents. However, male immigrants of lower social status had lower risk of attempted suicide than their native Danish peers.Young immigrants of both first and second generation status face serious challenges and vulnerabilities that western societies need to urgently address. Relative risk patterns for these adverse outcomes vary greatly between the genders and also by socioeconomic status. This high degree of heterogeneity points to the existence of modifiable factors that are amenable to positive change and a potential for effective intervention.

ContextThere have been many reports confirming the association between lower childhood socioeconomic circumstance and cardiovascular disease but evidence for links with cerebrovascular disease is contradictory. Hyperintensities on brain magnetic resonance imaging are associated with vascular risk factors, cognitive decline, dementia and death. However, the relationship between childhood socioeconomic circumstance and these lesions is unclear.ObjectiveTo test the hypothesis that childhood socioeconomic circumstance is associated with late life hyperintensity burden and that neither adult socioeconomic circumstance nor change in socioeconomic circumstance during life influence this effect.DesignCohort study.SettingCommunity.Participants227 community dwelling members of the 1936 Aberdeen Birth Cohort aged 68 years, who were free from dementia.Main outcome measuresRelationship between early life socioeconomic circumstance (paternal occupation) and abundance of late life brain hyperintensities.ResultsWe find significant negative correlations between childhood socioeconomic circumstance and white matter hyperintensities (ρ = -0.18, PConclusionsChildhood socioeconomic circumstance predicts the burden of brain white matter hyperintensities aged 68 years. The mechanism underlying this effect is unknown, but may act through fetal and/or early life programming of cerebrovascular disease. Future work to understand this vulnerability will inform strategies to reduce dementia and stroke.

We investigated the differences in brain fMRI signal complexity in patients with schizophrenia while performing the Cyberball social exclusion task, using measures of Sample entropy and Hurst exponent (H). 13 patients meeting diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) criteria for schizophrenia and 16 healthy controls underwent fMRI scanning at 1.5 T. The fMRI data of both groups of participants were pre-processed, the entropy characterized and the Hurst exponent extracted. Whole brain entropy and H maps of the groups were generated and analysed. The results after adjusting for age and sex differences together show that patients with schizophrenia exhibited higher complexity than healthy controls, at mean whole brain and regional levels. Also, both Sample entropy and Hurst exponent agree that patients with schizophrenia have more complex fMRI signals than healthy controls. These results suggest that schizophrenia is associated with more complex signal patterns when compared to healthy controls, supporting the increase in complexity hypothesis, where system complexity increases with age or disease, and also consistent with the notion that schizophrenia is characterised by a dysregulation of the nonlinear dynamics of underlying neuronal systems.

Most perceived parameters of sound (e.g. pitch, duration, timbre) can also be imagined in the absence of sound. These parameters are imagined more veridically by expert musicians than non-experts. Evidence for whether loudness is imagined, however, is conflicting. In music, the question of whether loudness is imagined is particularly relevant due to its role as a principal parameter of performance expression. This study addressed the hypothesis that the veridicality of imagined loudness improves with increasing musical expertise. Experts, novices and non-musicians imagined short passages of well-known classical music under two counterbalanced conditions: 1) while adjusting a slider to indicate imagined loudness of the music and 2) while tapping out the rhythm to indicate imagined timing. Subtests assessed music listening abilities and working memory span to determine whether these factors, also hypothesised to improve with increasing musical expertise, could account for imagery task performance. Similarity between each participant's imagined and listening loudness profiles and reference recording intensity profiles was assessed using time series analysis and dynamic time warping. The results suggest a widespread ability to imagine the loudness of familiar music. The veridicality of imagined loudness tended to be greatest for the expert musicians, supporting the predicted relationship between musical expertise and musical imagery ability.

The effects of selection on genome variation were investigated and visualized in tomato using a high-density single nucleotide polymorphism (SNP) array. 7,720 SNPs were genotyped on a collection of 426 tomato accessions (410 inbreds and 16 hybrids) and over 97% of the markers were polymorphic in the entire collection. Principal component analysis (PCA) and pairwise estimates of F(st) supported that the inbred accessions represented seven sub-populations including processing, large-fruited fresh market, large-fruited vintage, cultivated cherry, landrace, wild cherry, and S. pimpinellifolium. Further divisions were found within both the contemporary processing and fresh market sub-populations. These sub-populations showed higher levels of genetic diversity relative to the vintage sub-population. The array provided a large number of polymorphic SNP markers across each sub-population, ranging from 3,159 in the vintage accessions to 6,234 in the cultivated cherry accessions. Visualization of minor allele frequency revealed regions of the genome that distinguished three representative sub-populations of cultivated tomato (processing, fresh market, and vintage), particularly on chromosomes 2, 4, 5, 6, and 11. The PCA loadings and F(st) outlier analysis between these three sub-populations identified a large number of candidate loci under positive selection on chromosomes 4, 5, and 11. The extent of linkage disequilibrium (LD) was examined within each chromosome for these sub-populations. LD decay varied between chromosomes and sub-populations, with large differences reflective of breeding history. For example, on chromosome 11, decay occurred over 0.8 cM for processing accessions and over 19.7 cM for fresh market accessions. The observed SNP variation and LD decay suggest that different patterns of genetic variation in cultivated tomato are due to introgression from wild species and selection for market specialization.

Listener perceptions of changes in the arousal expressed by classical music have been found to correlate with changes in sound intensity/loudness over time. This study manipulated the intensity profiles of different pieces of music in order to test the causal nature of this relationship. Listeners (N = 38) continuously rated their perceptions of the arousal expressed by each piece. An extract from Dvorak's Slavonic Dance Opus 46 No 1 was used to create a variant in which the direction of change in intensity was inverted, while other features were retained. Even though it was only intensity that was inverted, perceived arousal was also inverted. The original intensity profile was also superimposed on three new pieces of music. The time variation in the perceived arousal of all pieces was similar to their intensity profile. Time series analyses revealed that intensity variation was a major influence on the arousal perception in all pieces, in spite of their stylistic diversity.

Significant progress has been achieved toward elucidating the molecular mechanisms that underlie breast cancer progression; yet, much less is known about the associated cellular biophysical traits. To this end, we use time-lapsed confocal microscopy to investigate the interplay among cell motility, three-dimensional (3D) matrix stiffness, matrix architecture, and transforming potential in a mammary epithelial cell (MEC) cancer progression series. We use a well characterized breast cancer progression model where human-derived MCF10A MECs overexpress either ErbB2, 14-3-3ζ, or both ErbB2 and 14-3-3ζ, with empty vector as a control. Cell motility assays showed that MECs overexpressing ErbB2 alone exhibited notably high migration speeds when cultured atop two-dimensional (2D) matrices, while overexpression of 14-3-3ζ alone most suppressed migration atop 2D matrices (as compared to non-transformed MECs). Our results also suggest that co-overexpression of the 14-3-3ζ and ErbB2 proteins facilitates cell migratory capacity in 3D matrices, as reflected in cell migration speed. Additionally, 3D matrices of sufficient stiffness can significantly hinder the migratory ability of partially transformed cells, but increased 3D matrix stiffness has a lesser effect on the aggressive migratory behavior exhibited by fully transformed cells that co-overexpress both ErbB2 and 14-3-3ζ. Finally, this study shows that for MECs possessing partial or full transforming potential, those overexpressing ErbB2 alone show the greatest sensitivity of cell migration speed to matrix architecture, while those overexpressing 14-3-3ζ alone exhibit the least sensitivity to matrix architecture. Given the current knowledge of breast cancer mechanobiology, these findings overall suggest that cell motility is governed by a complex interplay between matrix mechanics and transforming potential.

BACKGROUND: Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13) in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM). METHODOLOGY/PRINCIPAL FINDINGS: Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb) administered subcutaneously (s.c.). Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR) by invasive measurement of lung resistance (R(L)) and dynamic compliance (C(dyn)). Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P

Music is a vital part of most cultures and has a strong impact on emotions [1-5]. In Western cultures, emotive valence is strongly influenced by major and minor melodies and harmony (chords and their progressions) [6-13]. Yet, how pitch and harmony affect our emotions, and to what extent these effects are culturally mediated or universal, is hotly debated [2, 5, 14-20]. Here, we report an experiment conducted in a remote cloud forest region of Papua New Guinea, across several communities with similar traditional music but differing levels of exposure to Western-influenced tonal music. One hundred and seventy participants were presented with pairs of major and minor cadences (chord progressions) and melodies, and chose which of them made them happier. The experiment was repeated by 60 non-musicians and 19 musicians in Sydney, Australia. Bayesian analyses show that, for cadences, there is strong evidence that greater happiness was reported for major than minor in every community except one: the community with minimal exposure to Western-like music. For melodies, there is strong evidence that greater happiness was reported for those with higher mean pitch (major melodies) than those with lower mean pitch (minor melodies) in only one of the three PNG communities and in both Sydney groups. The results show that the emotive valence of major and minor is strongly associated with exposure to Western-influenced music and culture, although we cannot exclude the possibility of universality.

Glioblastoma is the most aggressive primary brain tumor leading to death in most of patients. It comprises almost 50-55% of all gliomas with an incidence rate of 2-3 per 100,000. Despite its rarity, overall mortality of glioblastoma is comparable to the most frequent tumors. The current standard treatment combines surgical resection, radiotherapy and chemotherapy with temozolomide. In spite of this aggressive multimodality protocol, prognosis of glioblastoma is poor and the median survival remains about 12-14.5 months. In this regard, new therapeutic approaches should be developed to improve the life quality and survival time of the patient after the initial diagnosis. Before switching to clinical trials in humans, all innovative therapeutic methods must be studied first on a relevant animal model in preclinical settings. In this regard, we validated the feasibility of intratumoral delivery of a holmium (Ho) microparticle suspension to an induced U87 glioblastoma model. Among the different radioactive beta emitters, 166Ho emits high-energy β(-) radiation and low-energy γ radiation. β(-) radiation is an effective means for tumor destruction and γ rays are well suited for imaging (SPECT) and consequent dosimetry. In addition, the paramagnetic Ho nucleus is a good asset to perform MRI imaging. In this study, five minipigs, implanted with our glioblastoma model were used to test the injectability of 165Ho (stable) using a bespoke injector and needle. The suspension was produced in the form of Ho microparticles and injected inside the tumor by a technique known as microbrachytherapy using a stereotactic system. At the end of this trial, it was found that the 165Ho suspension can be injected successfully inside the tumor with absence or minimal traces of Ho reflux after the injections. This injection technique and the use of the 165Ho suspension needs to be further assessed with radioactive 166Ho in future studies., Competing Interests: This work was supported by the BPifrance [ISI 2013–2018]. The funder provided support in the form of salaries for authors [Christophe Nennig, Lionel Marcon, Olivier Tillement, Hélène Gehan, Cédric Louis, Ilyes Zahi], and did have additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein interacting with anionic phospholipids and TAM tyrosine kinase receptors, is elevated in plasma of septic patients. Previous studies did not find different levels between survivors and non-survivors at admission because either they included a low number of patients (<50) or a low number of non-survivors (5%)., Objectives: To determine, in a larger cohort of septic patients comprising an expected number of non-survivors, the performance of the plasma level of Gas6 and its soluble receptor Axl (sAxl) within 24 hours of admission to predict in-ICU mortality., Patients: Septic adults with or without shock., Methods: Gas6 and sAxl were prospectively measured by ELISA at day 0, 3, 7, and then weekly until discharge or death., Results: We evaluated 129 septic patients, including 82 with and 47 without shock, with in-ICU mortality rate of 19.4% and in-hospital mortality rate of 26%. Gas6 level was higher in non-survivors than in survivors (238 vs. 167%, P = 0.003); this difference remained constant during the ICU stay. The area under the ROC curve for Gas6 (0.695 [95% CI: 0.58-0.81]) was higher than for sAxl, procalcitonin, CRP, IL-1beta, IL-6 and-alpha, and slightly higher than for IL-8, IL-10, SOFA and APACHEII scores in predicting in-ICU mortality. Considering 249% as a cut-off value, Gas6 measurement had a negative predictive value for mortality of 87%., Conclusion: It seems that Gas6 plasma level within 24 hours of ICU admission may predicts in-ICU mortality in patients with sepsis. If our result are confirmed in external validation, Gas6 plasma level measurement could contribute to the identification of patients who may benefit most from more aggressive management., Competing Interests: The authors have declared that no competing interests exists.