Socioeconomic inequalities in childhood exposure to secondhand smoke before and after smoke-free legislation in three UK countries

Background: Secondhand smoke (SHS) exposure is higher among lower socioeconomic status (SES) children. Legislation restricting smoking in public places has been associated with reduced childhood SHS exposure and increased smoke-free homes. This paper examines socioeconomic patterning in these changes.<p></p> Methods: Repeated cross-sectional survey of 10 867 schoolchildren in 304 primary schools in Scotland, Wales and Northern Ireland. Children provided saliva for cotinine assay, completing questionnaires before and 12 months after legislation.<p></p> Results: SHS exposure was highest, and private smoking restrictions least frequently reported, among lower SES children. Proportions of saliva samples containing <0.1 ng/ml (i.e. undetectable) cotinine increased from 31.0 to 41.0%. Although across the whole SES spectrum, there was no evidence of displacement of smoking into the home or increased SHS exposure, socioeconomic inequality in the likelihood of samples containing detectable levels of cotinine increased. Among children from the poorest families, 96.9% of post-legislation samples contained detectable cotinine, compared with 38.2% among the most affluent. Socioeconomic gradients at higher exposure levels remained unchanged. Among children from the poorest families, one in three samples contained > 3 ng/ml cotinine. Smoking restrictions in homes and cars increased, although socioeconomic patterning remained.<p></p> Conclusions Urgent action is needed to reduce inequalities in SHS exposure. Such action should include emphasis on reducing smoking in cars and homes

Pattern Informatics and its Application for Optimal Forecasting of Large Earthquakes in Japan

Pattern Informatics (PI) technique can be used to detect precursory seismic activation or quiescence and make an earthquake forecast. Here we apply the PI method for optimal forecasting of large earthquakes in Japan, using the data catalogue maintained by the Japan Meteorological Agency. The PI method is tested to forecast large (magnitude m ≥ 5) earthquakes spanning the time period 1995-2004 in the Kobe region. Visual inspection and statistical testing show that the optimized PI method has forecasting skill, relative to the seismic intensity data often used as a standard null hypothesis. Moreover, we find in a retrospective forecast that the 1995 Kobe earthquake (m = 7.2) falls in a seismically anomalous area. Another approach to test the forecasting algorithm is to create a future potential map for large (m ≥ 5) earthquake events. This is illustrated using the Kobe and Tokyo regions for the forecast period 2000-2009. Based on the resulting Kobe map we point out several forecasted areas: The epicentral area of the 1995 Kobe earthquake, the Wakayama area, the Mie area, and the Aichi area. The Tokyo forecast map was created prior to the occurrence of the Oct. 23, 2004 Niigata earthquake (m = 6.8) and the principal aftershocks with 5.0 ≤ m. We find that these events were close to in a forecasted area on the Tokyo map. The PI technique for regional seismicity observation substantiates an example showing considerable promise as an intermediate-term earthquake forecasting in Japa

Space-Time Clustering and Correlations of Major Earthquakes

Earthquake occurrence in nature is thought to result from correlated elastic stresses, leading to clustering in space and time. We show that occurrence of major earthquakes in California correlates with time intervals when fluctuations in small earthquakes are suppressed relative to the long term average. We estimate a probability of less than 1% that this coincidence is due to random clustering.Comment: 5 pages, 3 figures. Submitted to PR

Identification of diverse database subsets using property-based and fragment-based molecular descriptions

This paper reports a comparison of calculated molecular properties and of 2D fragment bit-strings when used for the selection of structurally diverse subsets of a file of 44295 compounds. MaxMin dissimilarity-based selection and k-means cluster-based selection are used to select subsets containing between 1% and 20% of the file. Investigation of the numbers of bioactive molecules in the selected subsets suggest: that the MaxMin subsets are noticeably superior to the k-means subsets; that the property-based descriptors are marginally superior to the fragment-based descriptors; and that both approaches are noticeably superior to random selection

Fluorescence correlation spectroscopy, combined with bimolecular fluorescence complementation, reveals the effects of β-arrestin complexes and endocytic targeting on the membrane mobility of neuropeptide Y receptors

Fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) analysis are powerful ways to study mobility and stoichiometry of G protein coupled receptor complexes, within microdomains of single living cells. However, relating these properties to molecular mechanisms can be challenging. We investigated the influence of β-arrestin adaptors and endocytosis mechanisms on plasma membrane diffusion and particle brightness of GFP-tagged neuropeptide Y (NPY) receptors. A novel GFP-based bimolecular fluorescence complementation (BiFC) system also identified Y1 receptor-β-arrestin complexes. Diffusion co-efficients (D) for Y1 and Y2-GFP receptors in HEK293 cell plasma membranes were 2.22 and 2.15×10−9 cm2 s−1 respectively. At a concentrationwhich promoted only Y1 receptor endocytosis, NPY treatment reduced Y1-GFPmotility (D 1.48×10−9 cm2 s−1), but did not alter diffusion characteristics of the Y2-GFP receptor. Agonist induced changes in Y1 receptor motility were inhibited by mutations (6A) which prevented β-arrestin recruitment and internalisation; conversely they became apparent in a Y2 receptor mutant with increased β-arrestin affinity. NPY treatment also increased Y1 receptor-GFP particle brightness, changes which indicated receptor clustering, and which were abolished by the 6A mutation. The importance of β-arrestin recruitment for these effects was illustrated by reduced lateral mobility (D 1.20–1.33×10−9 cm2 s−1) of Y1 receptor-β-arrestin BiFC complexes. Thus NPY-induced changes in Y receptormotility and brightness reflect early events surrounding arrestin dependent endocytosis at the plasma membrane, results supported by a novel combined BiFC/FCS approach to detect the underlying receptor-β-arrestin signalling complex

Reducing smoking in adolescents: cost-effectiveness results from the cluster randomized ASSIST (A Stop Smoking In Schools Trial)

Introduction: School-based smoking prevention programmes can be effective, but evidence on cost-effectiveness is lacking. We conducted a cost-effectiveness analysis of a school-based “peer-led” intervention.<p></p> Methods: We evaluated the ASSIST (A Stop Smoking In Schools Trial) programme in a cluster randomized controlled trial. The ASSIST programme trained students to act as peer supporters during informal interactions to encourage their peers not to smoke. Fifty-nine secondary schools in England and Wales were randomized to receive the ASSIST programme or usual smoking education. Ten thousand seven hundred and thirty students aged 12–13 years attended participating schools. Previous work has demonstrated that the ASSIST programme achieved a 2.1% (95% CI = 0%–4.2%) reduction in smoking prevalence. We evaluated the public sector cost, prevalence of weekly smoking, and cost per additional student not smoking at 24 months.<p></p> Results: The ASSIST programme cost of £32 (95% CI = £29.70–£33.80) per student. The incremental cost per student not smoking at 2 years was £1,500 (95% CI = £669–£9,947). Students in intervention schools were less likely to believe that they would be a smoker at age 16 years (odds ratio [OR] = 0.80; 95% CI = 0.66–0.96).<p></p> Conclusions: A peer-led intervention reduced smoking among adolescents at a modest cost. The intervention is cost-effective under realistic assumptions regarding the extent to which reductions in adolescent smoking lead to lower smoking prevalence and/or earlier smoking cessation in adulthood. The annual cost of extending the intervention to Year 8 students in all U.K. schools would be in the region of £38 million and could result in 20,400 fewer adolescent smokers.<p></p&gt

Fluorescence correlation spectroscopy, combined with bimolecular fluorescence complementation, reveals the effects of β-arrestin complexes and endocytic targeting on the membrane mobility of neuropeptide Y receptors

Fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) analysis are powerful ways to study mobility and stoichiometry of G protein coupled receptor complexes, within microdomains of single living cells. However, relating these properties to molecular mechanisms can be challenging. We investigated the influence of β-arrestin adaptors and endocytosis mechanisms on plasma membrane diffusion and particle brightness of GFP-tagged neuropeptide Y (NPY) receptors. A novel GFP-based bimolecular fluorescence complementation (BiFC) system also identified Y1 receptor-β-arrestin complexes. Diffusion co-efficients (D) for Y1 and Y2-GFP receptors in HEK293 cell plasma membranes were 2.22 and 2.15×10−9 cm2 s−1 respectively. At a concentrationwhich promoted only Y1 receptor endocytosis, NPY treatment reduced Y1-GFPmotility (D 1.48×10−9 cm2 s−1), but did not alter diffusion characteristics of the Y2-GFP receptor. Agonist induced changes in Y1 receptor motility were inhibited by mutations (6A) which prevented β-arrestin recruitment and internalisation; conversely they became apparent in a Y2 receptor mutant with increased β-arrestin affinity. NPY treatment also increased Y1 receptor-GFP particle brightness, changes which indicated receptor clustering, and which were abolished by the 6A mutation. The importance of β-arrestin recruitment for these effects was illustrated by reduced lateral mobility (D 1.20–1.33×10−9 cm2 s−1) of Y1 receptor-β-arrestin BiFC complexes. Thus NPY-induced changes in Y receptormotility and brightness reflect early events surrounding arrestin dependent endocytosis at the plasma membrane, results supported by a novel combined BiFC/FCS approach to detect the underlying receptor-β-arrestin signalling complex

Active power sharing in input-series-input-parallel output-series connected DC/DC converters

A high-capacity DC/DC converter with novel input-series-input-parallel output-series connection and with autonomous power sharing between modules is proposed. The proposed scheme is well suited for large-scale wind farm DC collection networks, as it avoids the charging current issues associated with its AC counterpart, and offers lower losses and reduced size and weight when a medium- or high-frequency transformer is used. Small-signal analysis is used to derive the control structures for the converter input and output stages. The proposed control scheme is validated through simulation and experimentation, including demonstration of autonomous power sharing between modules under several operating conditions

Modular input-series-input-parallel output-series DC/DC converter control with fault detection and redundancy

A novel high-power modular input-series-input-parallel output-series connected DC/DC converter for medium-voltage application is proposed. Emphasis has been placed on power sharing control to compensate parameter mismatches and achieve equal power distribution between modules. Converter control is extended to achieve fault-tolerant operation by exploiting modularity to provide redundancy in the event of any failure. The proposed control scheme is validated through application-level simulations and scaled-down experiments to testify the reliability of the proposed control for ensuring power sharing between modules under a range of operating conditions. The results validate the proposed converter and associated control scheme indicating this to be a promising topology for high-power medium-voltage applications