Long-Term Exposure to Wind Turbine Noise and Risk for Myocardial Infarction and Stroke:A Nationwide Cohort Study

Background: Noise from wind turbines (WTs) is reported as more annoying than traffic noise at similar levels, raising concerns as to whether WT noise (WTN) increases risk for cardiovascular disease, as observed for traffic noise. Objectives: We aimed to investigate whether long-term exposure to WTN increases risk of myocardial infarction (MI) and stroke. Methods: We identified all Danish dwellings within a radius 20 times the height of the closest WT and 25% of the dwellings within 20–40 times the height of the closest WT. Using data on WT type and simulated hourly wind at each WT, we estimated hourly outdoor and low frequency (LF) indoor WTN for each dwelling and derived 1-y and 5-y running nighttime averages. We used hospital and mortality registries to identify all incident cases of MI (n=19,145) and stroke (n=18,064) among all adults age 25–85 y (n=717,453), who lived in one of these dwellings for ≥one year over the period 1982–2013. We used Poisson regression to estimate incidence rate ratios (IRRs) adjusted for individual- and area-level covariates. Results: IRRs for MI in association with 5-y nighttime outdoor WTN ˃42 (vs. ˂24) dB(A) and indoor LF WTN ˃15 (vs. ˂5) dB(A) were 1.21 [95% confidence interval (CI): 0.91, 1.62; 47 exposed cases] and 1.29 (95% CI: 0.73, 2.28; 12 exposed cases), respectively. IRRs for intermediate categories of outdoor WTN [24–30, 30–36, and 36–42 dB(A) vs. ˂24 dB(A)] were slightly above the null and of similar size: 1.08 (95% CI: 1.04, 1.12), 1.07 (95% CI: 1.00, 1.12), and 1.06 (95% CI: 0.93, 1.22), respectively. For stroke, IRRs for the second and third outdoor exposure groups were similar to those for MI, but near or below the null for higher exposures. Conclusions: We did not find convincing evidence of associations between WTN and MI or stroke.</p

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

Impact of Long-Term Exposure to Wind Turbine Noise on Redemption of Sleep Medication and Antidepressants: A Nationwide Cohort Study

Background: Noise from wind turbines (WTs) is associated with annoyance and, potentially, sleep disturbances. Objectives: Our objective was to investigate whether long-term WT noise (WTN) exposure is associated with the redemption of prescriptions for sleep medication and antidepressants. Methods: For all Danish dwellings within a radius of 20-WT heights and for 25% of randomly selected dwellings within a radius of 20-to 40-WT heights, we estimated nighttime outdoor and low-frequency (LF) indoor WTN, using information on WT type and simulated hourly wind. During follow-up from 1996 to 2013, 68,696 adults redeemed sleep medication and 82,373 redeemed antidepressants, from eligible populations of 583,968 and 584,891, respectively. We used Poisson regression with adjustment for individual and area-level covariates. Results: Five-year mean outdoor nighttime WTN of ≥42 dB was associated with a hazard ratio (HR) = 1.14 [95% confidence interval (CI]: 0.98, 1.33) for sleep medication and HR = 1.17 (95% CI: 1.01, 1.35) for antidepressants (compared with exposure to WTN of ˂24 dB). We found no overall association with indoor nighttime LF WTN. In age-stratified analyses, the association with outdoor nighttime WTN was strongest among persons ≥65y of age, with HRs (95% CIs) for the highest exposure group (≥42 dB) of 1.68 (1.27, 2.21) for sleep medication and 1.23 (0.90, 1.69) for antidepressants. For indoor nighttime LF WTN, the HRs (95% CIs) among persons ≥65y of age exposed to ≥15 dB were 1.37 (0.81, 2.31) for sleep medication and 1.34 (0.80, 2.22) for antidepressants. Conclusions: We observed high levels of outdoor WTN to be associated with redemption of sleep medication and antidepressants among the elderly, suggesting that WTN may potentially be associated with sleep and mental health.</p

The piano music of Sterndale Bennett in the context of nineteenth-century pianism : a practice-based interpretive study with critical commentary

Sterndale Bennett (1816 - 75) made a significant contribution to piano music and pianism in London during the nineteenth-century, as evidenced by his substantial work list (see Appendix A). The aim of this thesis is to show how a knowledge of the performance practices of his time and of his own approach to style and interpretation can illuminate the performance of this repertoire. A secondary aim is to set this study within a clear historical framework and hence to make a strong connection between contextual and textual studies. An examination of his piano music and contemporary accounts of his piano playing reveal a conservative approach compared to other performers. The picture is amplified by an account of practices described in nineteenth-century writings on performance and of the differences between English and Viennese pianos. In the recordings, music by Sterndale Bennett is juxtaposed with music by selected predecessors and contemporaries, not only to show how his music relates to the nineteenth-century continuum, but also to present in sharp relief his special stylistic qualities. Some of the recordings reflect the work of members of the London Pianoforte School. The justification for this twentieth-century grouping is discussed in Chapter 1 in the context of London musical life and pianism in the nineteenthcentury, with reference to contemporary opinion-formers. The influence of Mozart and of the revival of Baroque keyboard music on Sterndale Bennett are also discussed. Publishing practices of the period are examined in Chapter 2, leading to a survey of Sterndale Bennett's sources and publications. Chapter 3 investigates approaches to nineteenth-century pianism, drawing on contemporary documents and secondary sources, comparing them with the preserved evidence we have regarding Sterndale Bennett's own stance on these matters. This process reveals, in many cases, that Sterndale Bennett represented a more scholarly and less commercial approach to piano playing than was prevalent among contemporaries such as Kalkbrenner, Thalberg and others. Finally, this study offers a paradigm for reinvigorating an historic but largely moribund repertoire incorporating it into contemporary practice.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Pain in the lumbar, thoracic or cervical regions: do age and gender matter? A population-based study of 34,902 Danish twins 20–71 years of age

Background. It is unclear to what extent spinal pain varies between genders and in relation to age. It was the purpose of this study to describe the self-reported prevalence of 1) pain ever and pain in the past year in each of the three spinal regions, 2) the duration of such pain over the past year, 3) pain radiating from these areas, and 4) pain in one, two or three areas. In addition, 5) to investigate if spinal pain reporting is affected by gender and 6) to see if it increases gradually with increasing age. Method. A cross-sectional survey was conducted in 2002 on 34,902 twin individuals, aged 20 to 71 years, representative of the general Danish population. Identical questions on pain were asked for the lumbar, thoracic and cervical regions. Results. Low back pain was most common, followed by neck pain with thoracic pain being least common. Pain for at least 30 days in the past year was reported by 12%, 10%, and 4%, respectively. The one-yr prevalence estimates of radiating pain were 22% (leg), 16% (arm), and 5% (chest). Pain in one area only last year was reported by 20%, followed by two (13%) and three areas (8%). Women were always more likely to report pain and they were also more likely to have had pain for longer periods. Lumbar and cervical pain peaked somewhat around the middle years but the curves were flatter for thoracic pain. Similar patterns were noted for radiating pain. Older people did not have pain in a larger number of areas but their pain lasted longer. Conclusion. Pain reported for and from the lumbar and cervical spines was found to be relatively common whereas pain in the thoracic spine and pain radiating into the chest was much less common. Women were, generally, more likely to report pain than men. The prevalence estimates changed surprisingly little over age and were certainly not more common in the oldest groups, although the pain was reported as more long-lasting in the older group

A Putative Plant Aminophospholipid Flippase, the Arabidopsis P4 ATPase ALA1, Localizes to the Plasma Membrane following Association with a β-Subunit

Plasma membranes in eukaryotic cells display asymmetric lipid distributions with aminophospholipids concentrated in the inner leaflet and sphingolipids in the outer leaflet. This unequal distribution of lipids between leaflets is, amongst several proposed functions, hypothesized to be a prerequisite for endocytosis. P4 ATPases, belonging to the P-type ATPase superfamily of pumps, are involved in establishing lipid asymmetry across plasma membranes, but P4 ATPases have not been identified in plant plasma membranes. Here we report that the plant P4 ATPase ALA1, which previously has been connected with cold tolerance of Arabidopsis thaliana, is targeted to the plasma membrane and does so following association in the endoplasmic reticulum with an ALIS protein β-subunit

Effects of perceived cocaine availability on subjective and objective responses to the drug

<p>Abstract</p> <p>Rationale</p> <p>Several lines of evidence suggest that cocaine expectancy and craving are two related phenomena. The present study assessed this potential link by contrasting reactions to varying degrees of the drug's perceived availability.</p> <p>Method</p> <p>Non-treatment seeking individuals with cocaine dependence were administered an intravenous bolus of cocaine (0.2 mg/kg) under 100% ('unblinded'; N = 33) and 33% ('blinded'; N = 12) probability conditions for the delivery of drug. Subjective ratings of craving, high, rush and low along with heart rate and blood pressure measurements were collected at baseline and every minute for 20 minutes following the infusions.</p> <p>Results</p> <p>Compared to the 'blinded' subjects, their 'unblinded' counterparts had similar craving scores on a multidimensional assessment several hours before the infusion, but reported higher craving levels on a more proximal evaluation, immediately prior to the receipt of cocaine. Furthermore, the 'unblinded' subjects displayed a more rapid onset of high and rush cocaine responses along with significantly higher cocaine-induced heart rate elevations.</p> <p>Conclusion</p> <p>These results support the hypothesis that cocaine expectancy modulates subjective and objective responses to the drug. Provided the important public health policy implications of heavy cocaine use, health policy makers and clinicians alike may favor cocaine craving assessments performed in the settings with access to the drug rather than in more neutral environments as a more meaningful marker of disease staging and assignment to the proper level of care.</p

Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory.

Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the alpha-keto-glutarate dehydrogenase catalyzed conversion of alpha-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2nd-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we demonstrate how systems biology tools coupled with directed evolution and selection allows non-intuitive, rapid and substantial re-direction of carbon fluxes in S. cerevisiae, and hence show proof of concept that this is a potentially attractive cell factory for over-producing different platform chemicals