Music in Reality The relation of music, emotion and Pre-Socratic myth

This thesis is in two sections. The first critically examines the tradition of harmonia mundi. The earliest complete and developed account of musica mundana appears in Plato, but numerous fragmented references appear in the pre-Socratic sources. The notion that harmonia mundi originated as an idea of quantitative speeds and distances of the celestial bodies, is discredited. Rather, it is shown that it more probably originates as an expression of an 'esoteric spiritual' teaching in which self-knowledge, death, the concept of harmonia, and consequently music, are related. The idea that the greatest importance of music rests on the relationship of music and emotion, is undermined in this context, and the relationship of music, emotion and experience is examined in a way that supports much of what was asserted by Hanslick in the nineteenth century. The interpretation of ancient sources is critically assessed in terms of common 'hermeneutic filters' which are shown to be inconsistent with the content and hence context of some of the sources. It is also argued that Plato should be approached not merely through the assessment of the arguments that appear in his discourses, but in the light of his portrayal of the life and death of Socrates. The discourses are treated as inexact, exoteric expressions of esoteric meaning, much of which can be gleaned from the 'symbol' and example of Socrates' own life and death. The second section presents an original music philosophy that is an entirely contemporary exposition of the essential meaning of the harmony of the spheres tradition, as interpreted in the first section. In this contemporary exposition, some of the ideas that appear in Plato concerning the relationship of soul, world and harmonia, are re-expressed in terms of self, world, and an original contemporary 'parable' for harmonia. The background to the ancient tradition, of the macrocosm-microcosm relationship, is brought into contemporary terms, drawing critically on some ideas of the quantum physicist David Bohm, and questions raised by quantum theory in general. Finally, the nature of the macrocosm-microcosm is related to parts of Wittgenstein 's Tractatus logico-philosophicus

Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis

Background A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). Methods A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size). Results In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant. Conclusions Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML

Atmospheric benzene observations from oil and gas production in the Denver-Julesburg Basin in July and August 2014

High time resolution measurements of volatile organic compounds (VOCs) were collected using a proton-transfer-reaction quadrupole mass spectrometry (PTR-QMS) instrument at the Platteville Atmospheric Observatory (PAO) in Colorado to investigate how oil and natural gas (O&amp;NG) development impacts air quality within the Wattenburg Gas Field (WGF) in the Denver-Julesburg Basin. The measurements were carried out in July and August 2014 as part of NASA’s “Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality” (DISCOVER-AQ) field campaign. The PTR-QMS data were supported by pressurized whole air canister samples and airborne vertical and horizontal surveys of VOCs. Unexpectedly high benzene mixing ratios were observed at PAO at ground level (mean benzene = 0.53 ppbv, maximum benzene = 29.3 ppbv), primarily at night (mean nighttime benzene = 0.73 ppbv). These high benzene levels were associated with southwesterly winds. The airborne measurements indicate that benzene originated from within the WGF, and typical source signatures detected in the canister samples implicate emissions from O&amp;NG activities rather than urban vehicular emissions as primary benzene source. This conclusion is backed by a regional toluene-to-benzene ratio analysis which associated southerly flow with vehicular emissions from the Denver area. Weak benzene-to-CO correlations confirmed that traffic emissions were not responsible for the observed high benzene levels. Previous measurements at the Boulder Atmospheric Observatory (BAO) and our data obtained at PAO allow us to locate the source of benzene enhancements between the two atmospheric observatories. Fugitive emissions of benzene from O&amp;NG operations in the Platteville area are discussed as the most likely causes of enhanced benzene levels at PAO

Toxicological and ecotoxicological risk‐based prioritization of pharmaceuticals in the natural environment

Approximately 1500 active pharmaceutical ingredients are currently in use; however, the environmental occurrence and impacts of only a small proportion of these have been investigated. Recognizing that it would be impractical to monitor and assess all pharmaceuticals that are in use, several previous studies have proposed the use of prioritization approaches to identify substances of most concern so that resources can be focused on these. All of these previous approaches suffer from limitations. In the present study, the authors draw on experience from previous prioritization exercises and present a holistic approach for prioritizing pharmaceuticals in the environment in terms of risks to aquatic and soil organisms, avian and mammalian wildlife, and humans. The approach considers both apical ecotoxicological endpoints as well as potential nonapical effects related to the therapeutic mode of action. Application of the approach is illustrated for 146 active pharmaceuticals that are used either in the community or in hospital settings in the United Kingdom. Using the approach, 16 compounds were identified as a potential priority. These substances include compounds belonging to the antibiotic, antidepressant, anti‐inflammatory, antidiabetic, antiobesity, and estrogen classes as well as associated metabolites. In the future, the prioritization approach should be applied more broadly around the different regions of the world. Environ Toxicol Chem 2016;9999:1–10. © 2016 SETA

Pesticides and Parkinson’s Disease—Is There a Link?

Parkinson’s disease (PD) is an idiopathic disease of the nervous system characterized by progressive tremor, bradykinesia, rigidity, and postural instability. It has been postulated that exogenous toxicants, including pesticides, might be involved in the etiology of PD. In this article we present a comprehensive review of the published epidemiologic and toxicologic literature and critically evaluate whether a relationship exists between pesticide exposure and PD. From the epidemiologic literature, there does appear to be a relatively consistent relationship between pesticide exposure and PD. This relationship appears strongest for exposure to herbicides and insecticides, and after long durations of exposure. Toxicologic data suggest that paraquat and rotenone may have neurotoxic actions that potentially play a role in the development of PD, with limited data for other pesticides. However, both the epidemiology and toxicology studies were limited by methodologic weaknesses. Particular issues of current and future interest include multiple exposures (both pesticides and other exogenous toxicants), developmental exposures, and gene–environment interactions. At present, the weight of evidence is sufficient to conclude that a generic association between pesticide exposure and PD exists but is insufficient for concluding that this is a causal relationship or that such a relationship exists for any particular pesticide compound or combined pesticide and other exogenous toxicant exposure

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Unexpected removal of the most neutral cationic pharmaceutical in river waters

Contamination of surface waters by pharmaceuticals is now widespread. There are few data on their environmental behaviour, particularly for those which are cationic at typical surface water pH. As the external surfaces of bacterio-plankton cells are hydrophilic with a net negative charge, it was anticipated that bacterio-plankton in surface-waters would preferentially remove the most extensively-ionised cation at a given pH. To test this hypothesis, the persistence of four, widely-used, cationic pharmaceuticals, chloroquine, quinine, fluphenazine and levamisole, was assessed in batch microcosms, comprising water and bacterio-plankton, to which pharmaceuticals were added and incubated for 21 days. Results show that levamisole concentrations decreased by 19 % in microcosms containing bacterio-plankton, and by 13 % in a parallel microcosm containing tripeptide as a priming agent. In contrast to levamisole, concentrations of quinine, chloroquine and fluphenazine were unchanged over 21 days in microcosms containing bacterio-plankton. At the river-water pH, levamisole is 28 % cationic, while quinine is 91–98 % cationic, chloroquine 99 % cationic and fluphenazine 72–86 % cationic. Thus, the most neutral compound, levamisole, showed greatest removal, contradicting the expected bacterio-plankton preference for ionised molecules. However, levamisole was the most hydrophilic molecule, based on its octanol–water solubility coefficient (K ow). Overall, the pattern of pharmaceutical behaviour within the incubations did not reflect the relative hydrophilicity of the pharmaceuticals predicted by the octanol–water distribution coefficient, D ow, suggesting that improved predictive power, with respect to modelling bioaccumulation, may be needed to develop robust environmental risk assessments for cationic pharmaceuticals