The evolution of popular music: USA 1960-2010.

(c) 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.In modern societies, cultural change seems ceaseless. The flux of fashion is especially obvious for popular music. While much has been written about the origin and evolution of pop, most claims about its history are anecdotal rather than scientific in nature. To rectify this, we investigate the US Billboard Hot 100 between 1960 and 2010. Using music information retrieval and text-mining tools, we analyse the musical properties of approximately 17 000 recordings that appeared in the charts and demonstrate quantitative trends in their harmonic and timbral properties. We then use these properties to produce an audio-based classification of musical styles and study the evolution of musical diversity and disparity, testing, and rejecting, several classical theories of cultural change. Finally, we investigate whether pop musical evolution has been gradual or punctuated. We show that, although pop music has evolved continuously, it did so with particular rapidity during three stylistic 'revolutions' around 1964, 1983 and 1991. We conclude by discussing how our study points the way to a quantitative science of cultural change.http://dx.doi.org/10.1098/rsos.15008

Viviparity Stimulates Diversification in an Order of Fish

International audienceSpecies richness is distributed unevenly across the tree of life and this may be influenced by the evolution of novel phenotypes that promote diversification. Viviparity has originated B150 times in vertebrates and is considered to be an adaptation to highly variable environments. Likewise, possessing an annual life cycle is common in plants and insects, where it enables the colonization of seasonal environments, but rare in vertebrates. The extent to which these reproductive life-history traits have enhanced diversification and their relative importance in the process remains unknown. We show that convergent evolution of viviparity causes bursts of diversification in fish. We built a phylogenetic tree for Cyprino-dontiformes, an order in which both annualism and viviparity have arisen, and reveal that while both traits have evolved multiple times, only viviparity played a major role in shaping the patterns of diversity. These results demonstrate that changes in reproductive life-history strategy can stimulate diversification

Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial

BACKGROUND: Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia. METHODS: This parallel-group, double-blind, placebo-controlled trial-the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)-was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897. FINDINGS: Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference -1·74, 95% CI -7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065). INTERPRETATION: This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme

Cost-effectiveness of mirtazapine for agitated behaviors in dementia: findings from a randomized controlled trial.

OBJECTIVES: To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up. DESIGN: Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo. SETTING: Community settings and care homes in 26 UK centers. PARTICIPANTS: People with probable or possible Alzheimer's disease and agitation. MEASUREMENTS: Primary outcome included incremental cost of participants' health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants' and unpaid carers' gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives. RESULTS: One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment. CONCLUSIONS: On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful

A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer’s disease and agitated behaviours: the HTA-SYMBAD trial

Background: Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics. Objectives: To assess clinical and cost-effectiveness and safety of mirtazapine and carbamazepine in treating agitation in dementia. Design: Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine over 12 weeks (carbamazepine arm discontinued). Setting: Twenty-six UK secondary care centres. Participants: Eligibility: probable or possible Alzheimer’s disease, agitation unresponsive to non-drug treatment, Cohen-Mansfield Agitation Inventory score ≥ 45. Interventions: Mirtazapine (target 45 mg), carbamazepine (target 300 mg) and placebo. Outcome measures: Primary: Cohen-Mansfield Agitation Inventory score 12 weeks post randomisation. Main economic outcome evaluation: incremental cost per six-point difference in Cohen-Mansfield Agitation Inventory score at 12 weeks, from health and social care system perspective. Data from participants and informants at baseline, 6 and 12 weeks. Long-term follow-up Cohen-Mansfield Agitation Inventory data collected by telephone from informants at 6 and 12 months. Randomisation and blinding: Participants allocated 1: 1: 1 ratio (to discontinuation of the carbamazepine arm, 1: 1 thereafter) to receive placebo or carbamazepine or mirtazapine, with treatment as usual. Random allocation was block stratified by centre and residence type with random block lengths of three or six (after discontinuation of carbamazepine, two or four). Double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, trial management team and research workers who did assessments were masked to group allocation. Results: Two hundred and forty-four participants recruited and randomised (102 mirtazapine, 102 placebo, 40 carbamazepine). The carbamazepine arm was discontinued due to slow overall recruitment; carbamazepine/placebo analyses are therefore statistically underpowered and not detailed in the abstract. Mean difference placebo-mirtazapine (−1.74, 95% confidence interval −7.17 to 3.69; p = 0.53). Harms: The number of controls with adverse events (65/102, 64%) was similar to the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group (n = 7) by week 16 than in the control group (n = 1). Post hoc analysis suggests this was of marginal statistical significance (p = 0.065); this difference did not persist at 6-and 12-month assessments. At 12 weeks, the costs of unpaid care by the dyadic carer were significantly higher in the mirtazapine than placebo group [difference: £1120 (95% confidence interval £56 to £2184)]. In the cost-effectiveness analyses, mean raw and adjusted outcome scores and costs of the complete cases samples showed no differences between groups. Limitations: Our study has four important potential limitations: (1) we dropped the proposed carbamazepine group; (2) the trial was not powered to investigate a mortality difference between the groups; (3) recruitment beyond February 2020, was constrained by the COVID-19 pandemic; and (4) generalisability is limited by recruitment of participants from old-age psychiatry services and care homes. Conclusions: The data suggest mirtazapine is not clinically or cost-effective (compared to placebo) for agitation in dementia. There is little reason to recommend mirtazapine for people with dementia with agitation. Future work: Effective and cost-effective management strategies for agitation in dementia are needed where non-pharmacological approaches are unsuccessful

Evidence for Metabolic Provisioning by a Common Invertebrate Endosymbiont, Wolbachia pipientis, during Periods of Nutritional Stress

Wolbachia are ubiquitous inherited endosymbionts of invertebrates that invade host populations by modifying host reproductive systems. However, some strains lack the ability to impose reproductive modification and yet are still capable of successfully invading host populations. To explain this paradox, theory predicts that such strains should provide a fitness benefit, but to date none has been detected. Recently completed genome sequences of different Wolbachia strains show that these bacteria may have the genetic machinery to influence iron utilization of hosts. Here we show that Wolbachia infection can confer a positive fecundity benefit for Drosophila melanogaster reared on iron-restricted or -overloaded diets. Furthermore, iron levels measured from field-collected flies indicated that nutritional conditions in the field were overall comparable to those of flies reared in the laboratory on restricted diets. These data suggest that Wolbachia may play a previously unrecognized role as nutritional mutualists in insects

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures

Adaptation of gastrointestinal nematode parasites to host genotype: single locus simulation models

Background: Breeding livestock for improved resistance to disease is an increasingly important selection goal. However, the risk of pathogens adapting to livestock bred for improved disease resistance is difficult to quantify. Here, we explore the possibility of gastrointestinal worms adapting to sheep bred for low faecal worm egg count using computer simulation. Our model assumes sheep and worm genotypes interact at a single locus, such that the effect of an A allele in sheep is dependent on worm genotype, and the B allele in worms is favourable for parasitizing the A allele sheep but may increase mortality on pasture. We describe the requirements for adaptation and test if worm adaptation (1) is slowed by non-genetic features of worm infections and (2) can occur with little observable change in faecal worm egg count. Results: Adaptation in worms was found to be primarily influenced by overall worm fitness, viz. the balance between the advantage of the B allele during the parasitic stage in sheep and its disadvantage on pasture. Genetic variation at the interacting locus in worms could be from de novo or segregating mutations, but de novo mutations are rare and segregating mutations are likely constrained to have (near) neutral effects on worm fitness. Most other aspects of the worm infection we modelled did not affect the outcomes. However, the host-controlled mechanism to reduce faecal worm egg count by lowering worm fecundity reduced the selection pressure on worms to adapt compared to other mechanisms, such as increasing worm mortality. Temporal changes in worm egg count were unreliable for detecting adaptation, despite the steady environment assumed in the simulations. Conclusions: Adaptation of worms to sheep selected for low faecal worm egg count requires an allele segregating in worms that is favourable in animals with improved resistance but less favourable in other animals. Obtaining alleles with this specific property seems unlikely. With support from experimental data, we conclude that selection for low faecal worm egg count should be stable over a short time frame (e.g. 20 years). We are further exploring model outcomes with multiple loci and comparing outcomes to other control strategies

Determinants of racial/ethnic differences in blood pressure management among hypertensive patients

BACKGROUND: Prior literature has shown that racial/ethnic minorities with hypertension may receive less aggressive treatment for their high blood pressure. However, to date there are few data available regarding the confounders of racial/ethnic disparities in the intensity of hypertension treatment. METHODS: We reviewed the medical records of 1,205 patients who had a minimum of two hypertension-related outpatient visits to 12 general internal medicine clinics during 7/1/01-6/30/02. Using logistic regression, we determined the odds of having therapy intensified by patient race/ethnicity after adjustment for clinical characteristics. RESULTS: Blacks (81.9%) and Whites (80.3%) were more likely than Latinos (71.5%) to have therapy intensified (P = 0.03). After adjustment for racial differences in the number of outpatient visits and presence of diabetes, there were no racial differences in rates of intensification. CONCLUSION: We found that racial/ethnic differences in therapy intensification were largely accounted for by differences in frequency of clinic visits and in the prevalence of diabetes. Given the higher rates of diabetes and hypertension related mortality among Hispanics in the U.S., future interventions to reduce disparities in cardiovascular outcomes should increase physician awareness of the need to intensify drug therapy more agressively in patients without waiting for multiple clinic visits, and should remind providers to treat hypertension more aggressively among diabetic patients