Aircraft based four-channel thermal dissociation laser induced fluorescence instrument for simultaneous measurements of NO2, total peroxy nitrate, total alkyl nitrate, and HNO3

A four-channel thermal dissociation laser induced fluorescence (TD-LIF) instrument has been developed for simultaneous measurements of nitrogen dioxide (NO2), total peroxy nitrate (∑PNs), total alkyl nitrate (∑ANs) and nitric acid (HNO3). NO2 is measured directly by LIF at 532 nm, whereas organic nitrates and nitric acid are thermally dissociated at distinct temperatures in the inlet to form NO2, which is then measured by LIF. The concentrations of each dissociated species are derived by the differences in measured NO2 relative to the reference colder inlet channel. The TD-LIF was adapted to fly on board the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe 146-301 atmospheric research aircraft in summer 2010, and to date has successfully flown in five field campaigns. This paper reports novel improvements in the TD-LIF instrumentations, including (1) the use of a single wavelength laser, which makes the system compact and relatively cheap; (2) the use of a single beam laser that allows easy alignment and optical stability against the vibrational aircraft environment; and (3) the optical assembly of four detection cells that allow simultaneous and fast (time resolution up to 0.1 s) measurements of NO2, ∑PNs, ∑ANs and HNO3. Laboratory-generated mixtures of PNs, ANs and HNO3 in zero air are converted into NO2 and used to fix the dissociation temperatures of each heated inlet to test the selectivity of the instrument and potential interferences due to recombination reactions of the dissociated products. The effectiveness of the TD-LIF was demonstrated during the RONOCO aircraft campaign (summer 2010). A chemiluminescence system that was measuring NO2 and a broadband cavity enhanced absorption spectrometer (BBCEAS) that was measuring one of the PNs (N2O5) were installed on the same aircraft during the campaign. The in-flight intercomparison of the new TD-LIF with the chemiluminescence system for NO2 measurements and the intercomparison between ∑PNs measured by the TD-LIF and N2O5 by the BBCEAS are used to assess the performance of the TD-LIF

Biohydrogenation of 22:6n-3 by Butyrivibrio proteoclasticus P18

Background: Rumen microbes metabolize 22:6n-3. However, pathways of 22:6n-3 biohydrogenation and ruminal microbes involved in this process are not known. In this study, we examine the ability of the well-known rumen biohydrogenating bacteria, Butyrivibrio fibrisolvens D1 and Butyrivibrio proteoclasticus P18, to hydrogenate 22:6n-3. Results: Butyrivibrio fibrisolvens D1 failed to hydrogenate 22:6n-3 (0.5 to 32 mu g/mL) in growth medium containing autoclaved ruminal fluid that either had or had not been centrifuged. Growth of B. fibrisolvens was delayed at the higher 22:6n-3 concentrations; however, total volatile fatty acid production was not affected. Butyrivibrio proteoclasticus P18 hydrogenated 22:6n-3 in growth medium containing autoclaved ruminal fluid that either had or had not been centrifuged. Biohydrogenation only started when volatile fatty acid production or growth of B. proteoclasticus P18 had been initiated, which might suggest that growth or metabolic activity is a prerequisite for the metabolism of 22:6n-3. The amount of 22:6n-3 hydrogenated was quantitatively recovered in several intermediate products eluting on the gas chromatogram between 22:6n-3 and 22:0. Formation of neither 22:0 nor 22:6 conjugated fatty acids was observed during 22:6n-3 metabolism. Extensive metabolism was observed at lower initial concentrations of 22:6n-3 (5, 10 and 20 mu g/mL) whereas increasing concentrations of 22:6n-3 (40 and 80 mu g/mL) inhibited its metabolism. Stearic acid formation (18:0) from 18:2n-6 by B. proteoclasticus P18 was retarded, but not completely inhibited, in the presence of 22:6n-3 and this effect was dependent on 22:6n-3 concentration. Conclusions: For the first time, our study identified ruminal bacteria with the ability to hydrogenate 22:6n-3. The gradual appearance of intermediates indicates that biohydrogenation of 22:6n-3 by B. proteoclasticus P18 occurs by pathways of isomerization and hydrogenation resulting in a variety of unsaturated 22 carbon fatty acids. During the simultaneous presence of 18:2n-6 and 22:6n-3, B. proteoclasticus P18 initiated 22:6n-3 metabolism before converting 18:1 isomers into 18:0

Incidence of first stroke and ethnic differences in stroke pattern in Bradford, UK: Bradford Stroke Study

Background: Information on ethnic disparities in stroke between White and Pakistani population in Europe is scarce. Bradford District has the largest proportion of Pakistani people in England; this provides a unique opportunity to study the difference in stroke between the two major ethnic groups. Aim: To determine the first-ever-stroke incidence and examine the disparities in stroke patterns between Whites and Pakistanis in Bradford. Methods: Prospective 12 months study consisting of 273,327 adults (≥18 years) residents. Stroke cases were identified by multiple overlapping approaches. Results: In the study period, 541 first-ever-strokes were recorded. The crude incidence rate was 198 per 100,000 person-years. Age adjusted-standardized rate to the World Health Organization world population of first-ever-stroke is 155 and 101 per 100,000 person-years in Pakistanis and Whites respectively. Four hundred and thirty-eight patients (81%) were Whites, 83 (15.3%) were Pakistanis, 11 (2%) were Indian and Bangladeshis, and 9 (1.7%) were of other ethnic origin. Pakistanis were significantly younger and had more obesity (p = 0.049), and diabetes mellitus (DM) (p = <0.001). They were less likely to suffer from atrial fibrillation (p = <0.001), be ex- or current smokers (p = <0.001), and drink alcohol above the recommended level (p = 0.007) compared with Whites. In comparison with Whites, higher rates of age-adjusted stroke (1.5-fold), lacunar infarction (threefold), and ischemic infarction due to large artery disease (twofold) were found in the Pakistanis. Conclusions: The incidence of first-ever-stroke is higher in the Pakistanis compared with the Whites in Bradford, UK. Etiology and vascular risk factors vary between the ethnic groups. This information should be considered when investigating stroke etiology, and when planning prevention and care provision to improve outcomes after stroke

Night-time measurements of HO<inf>x</inf> during the RONOCO project and analysis of the sources of HO<inf>2</inf>

Abstract. Measurements of the radical species OH and HO2 were made using the fluorescence assay by gas expansion (FAGE) technique during a series of night-time and daytime flights over the UK in summer 2010 and winter 2011. OH was not detected above the instrument's 1σ limit of detection during any of the night-time flights or during the winter daytime flights, placing upper limits on [OH] of 1.8 × 106 molecule cm−3 and 6.4 × 105 molecule cm−3 for the summer and winter flights, respectively. HO2 reached a maximum concentration of 3.2 × 108 molecule cm−3 (13.6 pptv) during a night-time flight on 20 July 2010, when the highest concentrations of NO3 and O3 were also recorded. An analysis of the rates of reaction of OH, O3, and the NO3 radical with measured alkenes indicates that the summer night-time troposphere can be as important for the processing of volatile organic compounds (VOCs) as the winter daytime troposphere. An analysis of the instantaneous rate of production of HO2 from the reactions of O3 and NO3 with alkenes has shown that, on average, reactions of NO3 dominated the night-time production of HO2 during summer and reactions of O3 dominated the night-time HO2 production during winter. This work was funded by the UK Natural Environment Research Council (NE/F004664/1). The authors would like to thank ground staff, engineers, scientists, and pilots involved in RONOCO for making this project a success. Airborne data were obtained using the BAe 146-301 Atmospheric Research Aircraft (ARA) flown by Directflight Ltd. and managed by the Facility for Airborne Atmospheric Measurements (FAAM), which is a joint entity of the Natural Environment Research Council (NERC) and the Met Office.This is the final version of the article. It first appeared from Copernicus Publications via http://dx.doi.org/10.5194/acp-15-8179-201

Unwanted incidents during transition of geriatric patients from hospital to home: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Geriatric patients recently discharged from hospital experience increased chance of unplanned readmissions and admission to nursing homes. Several studies have shown that medication-related discrepancies are common. Few studies report unwanted incidents by other factors than medications. In 2002 an ambulatory team (AT) was established within the Department of Geriatrics, St. Olavs University Hospital HF, Trondheim, Norway. The AT monitored the transition of the patients from hospital to home and four weeks after discharge in order to reveal unwanted incidents.</p> <p>The aim of the present study was to describe unwanted incidents registered by the AT among patients discharged from a geriatric evaluation and management unit (GEMU) by character, frequency and stage in the transitional process. Only unwanted incidents with a severity making contact with the primary health care (PHC) necessary were registered.</p> <p>Methods</p> <p>A prospective observational study with patients treated in the GEMU and followed by the AT was performed. Current practice included comprehensive geriatric assessment and management including discharge planning in the GEMU and collaboration with the primary health care on appointments on assistance to be provided after discharge from hospital. Unwanted incidents severe enough to induce contact with the primary health care were registered during the transitional phase and after discharge.</p> <p>Results</p> <p>118 patients (65% female), with mean age 83.2 ± 6.4 years participated. Median Barthel Index at discharge was 18 (interquartile range 16-19) and median Mini Mental Status Examination 24 (interquartile range 21-26). A total of 146 unwanted incidents were registered in 70 (59%) of the patients. Most frequent were unwanted incidents related to drug prescription regime (32%), exchange of information in and between the GEMU and the primary health care (25%) and service or help provided from the PHC (17%).</p> <p>Conclusions</p> <p>Despite a seemingly well-organised system for transition of patients from the GEMU to their homes, one or more unwanted incidents occurred in most patients during discharge or four weeks post discharge. The study has revealed areas of importance for improving transitional care of geriatric patients.</p

Fractional dynamics pharmacokinetics–pharmacodynamic models

While an increasing number of fractional order integrals and differential equations applications have been reported in the physics, signal processing, engineering and bioengineering literatures, little attention has been paid to this class of models in the pharmacokinetics–pharmacodynamic (PKPD) literature. One of the reasons is computational: while the analytical solution of fractional differential equations is available in special cases, it this turns out that even the simplest PKPD models that can be constructed using fractional calculus do not allow an analytical solution. In this paper, we first introduce new families of PKPD models incorporating fractional order integrals and differential equations, and, second, exemplify and investigate their qualitative behavior. The families represent extensions of frequently used PK link and PD direct and indirect action models, using the tools of fractional calculus. In addition the PD models can be a function of a variable, the active drug, which can smoothly transition from concentration to exposure, to hyper-exposure, according to a fractional integral transformation. To investigate the behavior of the models we propose, we implement numerical algorithms for fractional integration and for the numerical solution of a system of fractional differential equations. For simplicity, in our investigation we concentrate on the pharmacodynamic side of the models, assuming standard (integer order) pharmacokinetics

Night-time measurements of HOx during the RONOCO project and analysis of the sources of HO2

Measurements of the radical species OH and HO2 were made using the fluorescence assay by gas expansion (FAGE) technique during a series of night-time and daytime flights over the UK in summer 2010 and winter 2011. OH was not detected above the instrument's 1σ limit of detection during any of the night-time flights or during the winter daytime flights, placing upper limits on [OH] of 1.8 × 106 molecule cm−3 and 6.4 × 105 molecule cm−3 for the summer and winter flights, respectively. HO2 reached a maximum concentration of 3.2 × 108 molecule cm−3 (13.6 pptv) during a night-time flight on 20 July 2010, when the highest concentrations of NO3 and O3 were also recorded. An analysis of the rates of reaction of OH, O3, and the NO3 radical with measured alkenes indicates that the summer night-time troposphere can be as important for the processing of volatile organic compounds (VOCs) as the winter daytime troposphere. An analysis of the instantaneous rate of production of HO2 from the reactions of O3 and NO3 with alkenes has shown that, on average, reactions of NO3 dominated the night-time production of HO2 during summer and reactions of O3 dominated the night-time HO2 production during winter

Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar

More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Early pyloric stenosis: a case control study

Pyloric stenosis (PS) is rare in the first 2 weeks of life, often leading to delays in diagnosis and treatment. We conducted a case control study to delineate the characteristics of patients with early PS (EPS). In addition, we tested the hypothesis that patients with EPS present with a smaller pylorus than older patients. A database of all patients presenting with PS to a children’s hospital over a 5-year period (2002–2006) was obtained. Each patient admitted during the first 2 weeks of life (subject) was matched to a patient admitted after 4 weeks of age (control), with the same gender, electrolyte status, and treating surgeon. A single pediatric radiologist, blinded to patient age, reviewed all available ultrasounds retrospectively. Demographic, clinical, diagnostic, therapeutic, and outcome data were compared. During the study period, 278 pyloromyotomies were performed for PS. Sixteen patients (5.8%) presented with EPS between 2 and 14 days of life. EPS patients had a higher prevalence of positive family history (31 vs. 0%, P = 0.043), and breast milk feeding (75 vs. 31%, P = 0.045). Sonographic measurements showed a pylorus that was of significantly less length (17.1 ± 0.6 vs. 20.5 ± 0.9 mm, P = 0.006) and muscle thickness (3.5 ± 0.2 vs. 4.9 ± 0.2 mm, P &lt; 0.001) in patients with EPS. Hospital stay was significantly longer for EPS patients (4.3 ± 0.9 vs. 2.0 ± 0.1 days, P = 0.19) Babies presenting with EPS are more likely to be breast fed and to have a positive family history. EPS is associated with a longer hospital stay. Use of sonographic diagnostic measurements specific to this age group may prevent delays in diagnosis and treatment, and improve outcomes