Muonium addition reactions in the gas phase: Quantum tunneling in Mu + C2H4 and Mu + C2D4

Copyright © 1990 American Institute of Physics.The reaction kinetics for the addition of the muonium (Mu=μ+e−) atom to C2H4 and C2D4 have been measured over the temperature range 150–500 K at (N2) moderator pressures near 1 atm. A factor of about 8 variation in moderator pressure was carried out for C2H4, with no significant change seen in the apparent rate constant kapp, which is therefore taken to be at the high pressure limit, yielding the bimolecular rate constant kMu for the addition step. This is also expected from the nature of the μSR technique employed, which, in favorable cases, gives kapp=kMu at any pressure. Comparisons with the H atom data of Lightfoot and Pilling, and Sugawara et al. and the D atom data of Sugawara et al. reveal large isotope effects. Only at the highest temperatures, near 500 K, is kMu/kH given by its classical value of 2.9, from the mean velocity dependence of the collision rate but at the lowest temperatures kMu/kH≳30/1 is seen, reflecting the pronounced tunneling of the much lighter Mu atom (mμ=1/9 mp). The present Mu results should provide accurate tests of reaction theories on currently available ab initio surfaces.NSERC (Canada), the Canada Council for their awarding of a Killam Research Fellowship and the Meson Science Institute, Faculty of Science, University of Tokyo

Nitrates in drinking water and methemoglobin levels in pregnancy: a longitudinal study

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Private water systems are more likely to have nitrate levels above the maximum contaminant level (MCL). Pregnant women are considered vulnerable to the effects of exposure to high levels of nitrates in drinking water due to their altered physiological states. The level of methemoglobin in the blood is the biomarker often used in research for assessing exposure to nitrates. The objective of this study was to assess methemoglobin levels and examine how various factors affected methemoglobin levels during pregnancy. We also examined whether differences in water use practices existed among pregnant women based on household drinking water source of private vs. public supply. METHODS: A longitudinal study of 357 pregnant women was conducted. Longitudinal regression models were used to examine changes and predictors of the change in methemoglobin levels over the period of gestation. RESULTS: Pregnant women showed a decrease in methemoglobin levels with increasing gestation although <1% had levels above the physiologic normal of 2% methemoglobin, regardless of the source of their drinking water. The multivariable analyses did not show a statistically significant association between methemoglobin levels and the estimated nitrate intake from tap water among pregnant women around 36 weeks gestation (β = 0.046, p = 0.986). Four women had tap water nitrate levels above the MCL of 10 mg/L. At enrollment, a greater proportion of women who reported using water treatment devices were private wells users (66%) compared to public system users (46%) (p < 0.0001). Also, a greater proportion of private well users (27%) compared to public system users (13%) were using devices capable of removing nitrate from water (p < 0.0001). CONCLUSION: Pregnant women potentially exposed to nitrate levels primarily below the MCL for drinking water were unlikely to show methemoglobin levels above the physiologic normal. Water use practices such as the use of treatment devices to remove nitrates varied according to water source and should be considered in the assessment of exposure to nitrates in future studies

Fatal Cases of Influenza A in Childhood

In the northern hemisphere winter of 2003–04 antigenic variant strains (A/Fujian/411/02 –like) of influenza A H3N2 emerged. Circulation of these strains in the UK was accompanied by an unusually high number of laboratory confirmed influenza associated fatalities in children. This study was carried out to better understand risk factors associated with fatal cases of influenza in children.Case histories, autopsy reports and death registration certificates for seventeen fatal cases of laboratory confirmed influenza in children were analyzed. None had a recognized pre-existing risk factor for severe influenza and none had been vaccinated. Three cases had evidence of significant bacterial co-infection. Influenza strains recovered from fatal cases were antigenically similar to those circulating in the community. A comparison of protective antibody titres in age stratified cohort sera taken before and after winter 2003–04 showed that young children had the highest attack rate during this season (21% difference, 95% confidence interval from 0.09 to 0.33, p = 0.0009). Clinical incidences of influenza-like illness (ILI) in young age groups were shown to be highest only in the years when novel antigenic drift variants emerged.This work presents a rare insight into fatal influenza H3N2 in healthy children. It confirms that circulating seasonal influenza A H3N2 strains can cause severe disease and death in children in the apparent absence of associated bacterial infection or predisposing risk factors. This adds to the body of evidence demonstrating the burden of severe illness due to seasonal influenza A in childhood

CAM therapies among primary care patients using opioid therapy for chronic pain

<p>Abstract</p> <p>Background</p> <p>Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy.</p> <p>Method</p> <p>A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population.</p> <p>Results</p> <p>Patients were treated for a variety of pain problems including low back pain (38.4%), headaches (9.9%), and knee pain (6.5%); the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248), chiropractic treatment (17.8%, n = 162), acupuncture (7.6%, n = 69), yoga (6.1%, n = 55), herbs and supplements (6.8%, n = 62), and prolotherapy (5.9%, n = 54). CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8%) and prolotherapy (87.7%), whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful.</p> <p>Conclusion</p> <p>This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.</p

Predicting Pneumonia and Influenza Mortality from Morbidity Data

BACKGROUND: Few European countries conduct reactive surveillance of influenza mortality, whereas most monitor morbidity. METHODOLOGY/PRINCIPAL FINDINGS: We developed a simple model based on Poisson seasonal regression to predict excess cases of pneumonia and influenza mortality during influenza epidemics, based on influenza morbidity data and the dominant types/subtypes of circulating viruses. Epidemics were classified in three levels of mortality burden (“high”, “moderate” and “low”). The model was fitted on 14 influenza seasons and was validated on six subsequent influenza seasons. Five out of the six seasons in the validation set were correctly classified. The average absolute difference between observed and predicted mortality was 2.8 per 100,000 (18% of the average excess mortality) and Spearman's rank correlation coefficient was 0.89 (P = 0.05). CONCLUSIONS/SIGNIFICANCE: The method described here can be used to estimate the influenza mortality burden in countries where specific pneumonia and influenza mortality surveillance data are not available

A population based time series analysis of asthma hospitalisations in Ontario, Canada: 1988 to 2000

BACKGROUND: Asthma is a common yet incompletely understood health problem associated with a high morbidity burden. A wide variety of seasonally variable environmental stimuli such as viruses and air pollution are believed to influence asthma morbidity. This study set out to examine the seasonal patterns of asthma hospitalisations in relation to age and gender for the province of Ontario over a period of 12 years. METHODS: A retrospective, population-based study design was used to assess temporal patterns in hospitalisations for asthma from April 1, 1988 to March 31, 2000. Approximately 14 million residents of Ontario eligible for universal healthcare coverage during this time were included for analysis. Time series analyses were conducted on monthly aggregations of hospitalisations. RESULTS: There is strong evidence of an autumn peak and summer trough seasonal pattern occurring every year over the 12-year period (Fisher-Kappa (FK) = 23.93, p > 0.01; Bartlett Kolmogorov Smirnov (BKS) = 0.459, p < 0.01). This pattern was observed in both sexes. However, young males (0–4 years) were hospitalised at two to three times the rate of females of the same age. Rates were much lower in the older age groups. A downward trend in asthma hospitalisations was observed in the total population over the twelve-year period (beta = -0.980, p < 0.01). CONCLUSIONS: A clear and consistent seasonal pattern was observed in this study for asthma hospitalisations. These findings have important implications for the development of effective management and prevention strategies

Surveillance recommendations based on an exploratory analysis of respiratory syncytial virus reports derived from the European Influenza Surveillance System

BACKGROUND: Respiratory syncytial virus (RSV) is an important pathogen that can cause severe illness in infants and young children. In this study, we assessed whether data on RSV collected by the European Influenza Surveillance Scheme (EISS) could be used to build an RSV surveillance system in Europe. METHODS: Influenza and RSV data for the 2002–2003 winter season were analysed for England, France, the Netherlands and Scotland. Data from sentinel physician networks and other sources, mainly hospitals, were collected. Respiratory specimens were tested for influenza and RSV mainly by virus culture and polymerase chain reaction amplification. RESULTS: Data on RSV were entered timely into the EISS database. RSV contributed noticeably to influenza-like illness: in England sentinel RSV detections were common in all age groups, but particularly in young children with 20 (40.8%) of the total number of sentinel swabs testing positive for RSV. Scotland and France also reported the highest percentages of RSV detections in the 0–4 year age group, respectively 10.3% (N = 29) and 12.2% (N = 426). In the Netherlands, RSV was detected in one person aged over 65 years. CONCLUSION: We recommend that respiratory specimens collected in influenza surveillance are also tested systematically for RSV and emphasize the use of both community derived data and data from hospitals for RSV surveillance. RSV data from the EISS have been entered in a timely manner and we consider that the EISS model can be used to develop an RSV surveillance system equivalent to the influenza surveillance in Europe

A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct emx2 mutant phenotype

<p>Abstract</p> <p>Background</p> <p>The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p> <p>Results</p> <p>To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it>tau-lacZ </it>reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it>reeler</it>. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it>Emx2 </it>gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p> <p>Conclusions</p> <p>These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it>Emx2 </it>mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p> <p>See Commentary: <url>http://www.biomedcentral.com/1741-7007/9/1</url></p

IGF-1 receptor antagonism inhibits autophagy

Inhibition of the insulin/insulin-like growth factor signalling pathway increases lifespan and protects against neurodegeneration in model organisms, and has been considered as a potential therapeutic target. This pathway is upstream of mTORC1, a negative regulator of autophagy. Thus, we expected autophagy to be activated by insulin-like growth factor-1 (IGF-1) inhibition, which could account for many of its beneficial effects. Paradoxically, we found that IGF-1 inhibition attenuates autophagosome formation. The reduced amount of autophagosomes present in IGF-1R depleted cells can be, at least in part, explained by a reduced formation of autophagosomal precursors at the plasma membrane. In particular, IGF-1R depletion inhibits mTORC2, which, in turn, reduces the activity of protein kinase C (PKCa/b). This perturbs the actin cytoskeleton dynamics and decreases the rate of clathrin-dependent endocytosis, which impacts autophagosome precursor formation. Finally, with important implications for human diseases, we demonstrate that pharmacological inhibition of the IGF-1R signalling cascade reduces autophagy also in zebrafish and mice models. The novel link we describe here has important consequences for the interpretation of genetic experiments in mammalian systems and for evaluating the potential of targeting the IGF-1R receptor or modulating its signalling through the downstream pathway for therapeutic purposes under clinically relevant conditions, such as neurodegenerative diseases, where autophagy stimulation is considered beneficial.This is the version of the manuscript that was first published on line. The final version can be found published in Human Molecular Genetics by OUP here: http://hmg.oxfordjournals.org/content/22/22/4528.full.pdf+html