It's not what you play, it's how you play it: timbre affects perception of emotion in music.

Salient sensory experiences often have a strong emotional tone, but the neuropsychological relations between perceptual characteristics of sensory objects and the affective information they convey remain poorly defined. Here we addressed the relationship between sound identity and emotional information using music. In two experiments, we investigated whether perception of emotions is influenced by altering the musical instrument on which the music is played, independently of other musical features. In the first experiment, 40 novel melodies each representing one of four emotions (happiness, sadness, fear, or anger) were each recorded on four different instruments (an electronic synthesizer, a piano, a violin, and a trumpet), controlling for melody, tempo, and loudness between instruments. Healthy participants (23 young adults aged 18-30 years, 24 older adults aged 58-75 years) were asked to select which emotion they thought each musical stimulus represented in a four-alternative forced-choice task. Using a generalized linear mixed model we found a significant interaction between instrument and emotion judgement with a similar pattern in young and older adults (p < .0001 for each age group). The effect was not attributable to musical expertise. In the second experiment using the same melodies and experimental design, the interaction between timbre and perceived emotion was replicated (p < .05) in another group of young adults for novel synthetic timbres designed to incorporate timbral cues to particular emotions. Our findings show that timbre (instrument identity) independently affects the perception of emotions in music after controlling for other acoustic, cognitive, and performance factors

Chlorantraniliprole (Rynaxypyr): A novel DuPont™ insecticide with low toxicity and low risk for honey bees (Apis mellifera) and bumble bees (Bombus terrestris) providing excellent tools for uses in integrated pest management

contribution to session IVTest methodology Background: The effects on bees of chlorantraniliprole (DPX-E2Y45, DuPont™ Rynaxypyr), a new anthranilic diamide insecticide with a novel and very specific mode of action activating insect ryanodine receptors were investigated.Results: Acute toxicity tests with chlorantraniliprole and the formulations, Coragen and Altacor, demonstrated low intrinsic toxicity to honey bees. Low risk for honey bees was demonstrated in semi-field tunnel tests with flowering Phacelia or wheat (with daily sprays of sugar solution to simulate honey dew) at application rates of Coragen of up to 60 g chlorantraniliprole/ha. Low potential of systemic exposure via pollen and nectar of honeybees to chlorantraniliprole was documented in a residue Phacelia tunnel trial with chlorantraniliprole applied to and mixed into bare soil. The impact of Altacor on bumble bees was studied in a greenhouse test in tomato at 40 g chlorantraniliprole/ha. Bumble bees directly over-sprayed during foraging activity with chlorantraniliprole or exposed to treated plants behaved as controls. Conclusion: Chlorantraniliprole formulations provide excellent tools for integrated pest management (IPM) programmes to conserve pollinating honey bees and bumble bees. Keywords: Chlorantraniliprole, Rynaxypyr®, insecticide, side-effects, honey bee, bumble bee, integrated pest management (IPM

Adaptation to Different Human Populations by HIV-1 Revealed by Codon-Based Analyses

Several codon-based methods are available for detecting adaptive evolution in protein-coding sequences, but to date none specifically identify sites that are selected differentially in two populations, although such comparisons between populations have been historically useful in identifying the action of natural selection. We have developed two fixed effects maximum likelihood methods: one for identifying codon positions showing selection patterns that persist in a population and another for detecting whether selection is operating differentially on individual codons of a gene sampled from two different populations. Applying these methods to two HIV populations infecting genetically distinct human hosts, we have found that few of the positively selected amino acid sites persist in the population; the other changes are detected only at the tips of the phylogenetic tree and appear deleterious in the long term. Additionally, we have identified seven amino acid sites in protease and reverse transcriptase that are selected differentially in the two samples, demonstrating specific population-level adaptation of HIV to human populations

Predicting the costs of managing patients with chronic obstructive pulmonary disease

SummaryThe economic consequences of chronic obstructive pulmonary disease (COPD) are considerable, although the factors that best predict costs are largely unknown. This study used a population-based cohort to identify the clinical factors during an index year that were most predictive of increased direct medical costs in the subsequent year, and to develop a predictive model that described the cost variations in COPD.The medical records of 2116 patients enrolled in one regional health system who had COPD and healthcare resource utilisation data for 1998 and 1999, were abstracted for information about symptoms, smoking history, chronic illnesses, and pulmonary function data. All inpatient, outpatient and pharmacy utilisation data for each subject for 1999 were extracted from the database. Total costs for each individual were transformed to a log scale. Potential causes of cost variability (predictor variables) were defined and classified into sets (or domains). Multiple linear regression models were fitted for each domain.The study demonstrated that severity of airflow obstruction, as assessed by FEV1% predicted, is a significant but weak predictor of future healthcare resource utilisation—prior hospitalisation and home oxygen use, the presence of comorbid conditions and symptoms of dyspnoea are better predictors of costs. Those interested in the economic benefits of new COPD treatments and disease management programs need to carefully account for these factors

Effect of adiposity on differences in carotid plaque burden in studies conducted in Norway and Russia: a cross-sectional analysis of two populations at very different risk of cardiovascular mortality

Objectives - Large differences exist in the burden of cardiovascular disease (CVD) between Russia and Western European countries including Norway. Obesity prevalence may contribute to the differences. We investigated whether difference in the level of adiposity, assessed using body mass index and waist-to-hip ratio(WHR), could explain intercountry differences in the burden of carotid plaque, a measure of atherosclerosis, in the populations. Design - Cross-sectional analysis. Logistic and linear regression models were used. Setting - We used population-based cross-sectional Know Your Heart (KYH) study in Russia and the Tromsø 7 study (Tromsø 7) in Norway. Participants - 3262 and 1800 men and women aged 40–69 years in KYH and Tromsø 7, respectively. Primary and secondary outcome - The presence of carotid plaques and plaque score assessed using ultrasound. Results - The presence of carotid plaques and plaque score were higher in KYH than Tromsø 7 regardless of age group and sex. A positive association between carotid plaque burden and adiposity was found (OR of having at least one plaque per SD in WHR 1.18 (95% CI 1.06 to 1.31) for men; 1.15 (1.06 to 1.25) for women)) adjusted for age, smoking and education in a pooled analysis of the two studies. There was little evidence of the interaction between study and adiposity. These effects did not differ between the two studies. However, neither adiposity nor CVD risk factors (smoking, systolic blood pressure, cholesterol, glycosylated haemoglobin) explained the higher carotid plaque burden in KYH compared with Tromsø 7. Conclusion - Adiposity, especially abdominal adiposity, is a risk factor for carotid plaque in Russia and Norway, although neither adiposity nor established CVD risk factors explained the higher plaque burden in Russia. To reduce the CVD burden in Russia, beyond prevention and treatment of adiposity, further research is required to understand why Russia has a high burden of atherosclerosis

Dependence of Bone Yield (Volume of Bone Formed per Unit of Cement Surface Area) on Resorption Cavity Size During Osteonal Remodeling in Human Rib: Implications for Osteoblast Function and the Pathogenesis of Age-Related Bone Loss

It is both a necessary and a sufficient condition for bone to be lost with age at any surface location that during remodeling the replacement of resorbed bone is incomplete. In both the ilium and the rib, the degree of such focal imbalance is smaller on the intracortical than on the endocortical or cancellous surfaces that are adjacent to bone marrow. The reason for this difference is unknown. To further examine this question, we measured various geometric variables in 1263 osteons in rib cross sections from 65 persons, including both sexes and age ranges 20 to 30 years and 60 to 70 years (four groups). Haversian canal (HC) area did not differ significantly between sexes or age groups. Percent osteonal refilling was close to 95% in all groups and did not differ between sexes but fell slightly with age. There was a very highly significant linear relationship between osteon bone area and (osteon area + HC area) in all groups, with coefficients of determination (r2) greater than 0.98. The regression slopes declined slightly with age in women but not in men. There was a very highly significant quadratic relationship between osteon bone area and osteon perimeter in all groups, with r2 values greater than 0.97. The ratio osteon bone area:osteon perimeter, an index of bone yield—the volume of bone deposited on each unit area of cement surface—was strongly related to osteon area and did not differ between sexes but was slightly less in the older groups. We conclude the following: (1) The high efficiency of intracortical remodeling in the rib is confirmed, with only trivial effects of age. (2) For HC area to be maintained within narrow limits and bone balance preserved, either initial osteoblast density or osteoblast capacity (the two determinants of bone yield) or, most likely, both must increase progressively with the size of the resorption cavity, suggesting that osteoblast recruitment (relative to available surface) and osteoblast lifespan increase with the volume of bone resorbed. (3) Intracortical remodeling in the rib is more efficient than marrow-adjacent remodeling at any site, possibly because of the different relationships to the circulation. In osteonal remodeling, all molecules released from resorbed bone must travel past the sites of osteoblast recruitment and operation, but in hemiosteonal remodeling, some molecules may not be subject to this constraint. (4) If marrow-adjacent remodeling became as efficient as rib intracortical remodeling, age-related bone loss would cease to be an important medical problem. © 2010 American Society for Bone and Mineral Researc

Effects of seed lots and seed production time on growth, flowering and cut flower quality in Bupleurum rotundifolium L.

Effects of three planting patterns; two-row-planting high density (25 plants·m(-2)), two-row-planting low density (12.5 plants·m(-2)), and four-row-planting (25 plants·m(-2)) on the cut flower number and quality of spray carnation (Dianthus caryophyllus L.) cv. ‘Barbara’ and ‘Cherry Tessino’ grown by fertigation cultivation were investigated. In ‘Barbara’, there was no difference in total cut flower number between two-row-planting high density and four-row-planting. Total cut flower number of two-row-planting low density decreased to 60% of two-row-planting high density or four-row-planting. In ‘Cherry Tessino’, the total cut flower number of two-row-planting high density was 15% more than that of four-row-planting. The total cut flower number of two-row-planting low density decreased to 60~70% of two-row-planting high density or four-row-planting. There was no difference in cut flower quality between two-row-planting high density and four-row-planting in both cultivars. Cut flower weight and stem diameter of two-row-planting low density increased compared to those of two-row-planting high density or four-row-planting. Thus, the result indicates that two-row-planting high density may be suitable for fertigation cultivation in carnation

Long-term use of Everolimus in patients with Tuberous Sclerosis Complex: final results from the EXIST-1 study

BACKGROUND: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs) and other manifestations of tuberous sclerosis complex (TSC). However, long-term use of mTOR inhibitors might be necessary. This analysis explored long-term efficacy and safety of everolimus from the conclusion of the EXIST-1 study (NCT00789828). Methods and FINDINGS: EXIST-1 was an international, prospective, double-blind, placebo-controlled phase 3 trial examining everolimus in patients with new or growing TSC-related SEGA. After a double-blind core phase, all remaining patients could receive everolimus in a long-term, open-label extension. Everolimus was initiated at a dose (4.5 mg/m 2 /day) titrated to a target blood trough of 5-15 ng/mL. SEGA response rate (primary end point) was defined as the proportion of patients achieving confirmed ≥50% reduction in the sum volume of target SEGA lesions from baseline in the absence of worsening nontarget SEGA lesions, new target SEGA lesions, and new or worsening hydrocephalus. Of 111 patients (median age, 9.5 years) who received ≥1 dose of everolimus (median duration, 47.1 months), 57.7% (95% confidence interval [CI], 47.9-67.0) achieved SEGA response. Of 41 patients with target renal angiomyolipomas at baseline, 30 (73.2%) achieved renal angiomyolipoma response. In 105 patients with ≥1 skin lesion at baseline, skin lesion response rate was 58.1%. Incidence of adverse events (AEs) was comparable with that of previous reports, and occurrence of emergent AEs generally decreased over time. The most common AEs (≥30% incidence) suspected to be treatment-related were stomatitis (43.2%) and mouth ulceration (32.4%). CONCLUSIONS: Everolimus use led to sustained reduction in tumor volume, and new responses were observed for SEGA and renal angiomyolipoma from the blinded core phase of the study. These findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a significant proportion of patients. Trial Registration ClinicalTrials.gov NCT0078982

Transmitted Drug Resistance in the CFAR Network of Integrated Clinical Systems Cohort: Prevalence and Effects on Pre-Therapy CD4 and Viral Load

Human immunodeficiency virus type 1 (HIV-1) genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR) in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL) and CD4+ cell count (CD4) at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT) were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184) were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I ( pVL) and D67N/G ( and pVL) were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1 infections and our understanding of the ongoing adaptation of HIV-1 to human populations

The business of cultural heritage tourism: critical success factors

This paper explores critical success factors (CSFs) required for cultural heritage tourism (CHT) operation and how these relate to commercial focus. The literature indicates tension between conservation of authenticity and commercial focus as it is seen to undermine authenticity, potentially degrading its quality and ultimate success as a tourism product. A list of nine key CHT business success factors was devised based on the published literature. Managers and operators of a range of Australian CHT operations were interviewed regarding achievement of CSFs. The operations were broadly categorised according to the level of commercial focus. The level of commercial focus was cross tabulated with the number of CHT business CSFs achieved. While all places in this study had addressed authenticity, CHT places presenting highly commercialised products tended to meet the criteria for achieving a greater number of CSFs than their less commercialised counter-parts. This has implications for sustainable CHT operation practices