Origins and composition of fine atmospheric carbonaceous aerosol in the Sierra Nevada Mountains, California

In this paper we report chemically resolved measurements of organic aerosol (OA) and related tracers during the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX) at the Blodgett Forest Research Station, California from 15 August–10 October 2007. OA contributed the majority of the mass to the fine atmospheric particles and was predominately oxygenated (OOA). The highest concentrations of OA were during sporadic wildfire influence when aged plumes were impacting the site. In situ measurements of particle phase molecular markers were dominated by secondary compounds and along with gas phase compounds could be categorized into six factors or sources: (1) aged biomass burning emissions and oxidized urban emissions, (2) oxidized urban emissions (3) oxidation products of monoterpene emissions, (4) monoterpene emissions, (5) anthropogenic emissions and (6) local methyl chavicol emissions and oxidation products. There were multiple biogenic components that contributed to OA at this site whose contributions varied diurnally, seasonally and in response to changing meteorological conditions, e.g. temperature and precipitation events. Concentrations of isoprene oxidation products were larger when temperatures were higher during the first half of the campaign (15 August–12 September) due to more substantial emissions of isoprene and enhanced photochemistry. The oxidation of methyl chavicol, an oxygenated terpene emitted by ponderosa pine trees, contributed similarly to OA throughout the campaign. In contrast, the abundances of monoterpene oxidation products in the particle phase were greater during the cooler conditions in the latter half of the campaign (13 September–10 October), even though emissions of the precursors were lower, although the mechanism is not known. OA was correlated with the anthropogenic tracers 2-propyl nitrate and carbon monoxide (CO), consistent with previous observations, while being comprised of mostly non-fossil carbon (>75%). The correlation between OA and an anthropogenic tracer does not necessarily identify the source of the carbon as being anthropogenic but instead suggests a coupling between the anthropogenic and biogenic components in the air mass that might be related to the source of the oxidant and/or the aerosol sulfate. Observations of organosulfates of isoprene and α-pinene provided evidence for the likely importance of aerosol sulfate in spite of neutralized aerosol although acidic plumes might have played a role upwind of the site. This is in contrast to laboratory studies where strongly acidic seed aerosols were needed in order to form these compounds. These compounds together represented only a minor fraction (<1%) of the total OA mass, which may be the result of the neutralized aerosol at the site or because only a small number of organosulfates were quantified. The low contribution of organosulfates to total OA suggests that other mechanisms, e.g. NO_x enhancement of oxidant levels, are likely responsible for the majority of the anthropogenic enhancement of biogenic secondary organic aerosol observed at this site

Scenario planning for the Edinburgh city region

This paper examines the application of scenario planning techniques to the detailed and daunting challenge of city re-positioning when policy makers are faced with a heavy history and a complex future context. It reviews a process of scenario planning undertaken in the Edinburgh city region, exploring the scenario process and its contribution to strategies and policies for city repositioning. Strongly rooted in the recent literature on urban and regional economic development, the text outlines how key individuals and organisations involved in the process participated in far-reaching analyses of the possible future worlds in which the Edinburgh city region might find itself

F2 slope as a perceptual cue for the front-back contrast in Standard Southern British English

Acoustic studies of several languages indicate that second-formant (F2) slopes in high vowels have opposing directions (independent of consonantal context): front [iː]-like vowels are produced with a rising F2 slope while back [uː]-like vowels are produced with a falling F2 slope. The present study first reports acoustic measurements that confirm this pattern for the English variety of Standard Southern British English (SSBE), where /uː/ has shifted from the back to the front area of the vowel space and is now realized with higher midpoint F2 values than several decades ago. Subsequently, we test whether the direction of F2 slope also serves as a reliable cue to the /iː/-/uː/ contrast in perception. The findings show that F2 slope direction is used as a cue (additional to midpoint formant values) to distinguish /iː/ from /uː/ by both young and older SSBE listeners: an otherwise ambiguous token is identified as /iː/ if it has a rising F2 slope and as /uː/ if it has a falling F2 slope. Furthermore, our results indicate that listeners generalize their reliance on F2 slope to other contrasts, namely /ɛ/-/ɒ/ and /æ/-/ɒ/, even though F2 slope is not employed to differentiate these vowels in production. This suggests that in SSBE, a rising F2 seems to be perceptually associated with an abstract feature such as [+front] while a falling F2 with an abstract feature such as [-front]

Anti-nociceptive and desensitizing effects of olvanil on capsaicin-induced thermal hyperalgesia in the rat

Background: Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient of capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as a potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of chronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root ganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in vivo; potential contributions of the cannabinoid CB1 receptor to olvanil’s anti-hyperalgesic effects were also investigated. Methods: A hot plate analgesia meter was used to evaluate the anti-nociceptive effects of olvanil on capsaicin-induced thermal hyperalgesia and the role played by CB1 receptors in mediating these effects. Single cell calcium imaging studies of DRG neurons were employed to determine the desensitizing effects of olvanil on capsaicin-evoked calcium responses. Statistical analysis used Student’s t test or one way ANOVA followed by Dunnett’s post-hoctest as appropriate. Results: Both olvanil (100 nM) and capsaicin (100 nM) produced significant increases in intracellular calcium concentrations [Ca2+]I in cultured DRG neurons. Olvanil was able to des ensitise TRPV1 responses to further capsaicin exposure more effectively than capsaicin. Intra plantar injection of capsaicin (0.1, 0.3 and 1μg) produced a robust TRPV1-dependant thermal hyperalgesia in rats, whilst olvanil (0.1, 0.3 and 1μg) produced no hyperalgesia, emphasizing its lack of pungency. The highest dose of olvanil significantly reduced the hyperalgesic effects of capsaicin in vivo. Intraplantar injection of the selective cannabinoid CB1 receptor antagonist rimonabant (1μg) altered neither capsaicin-induced thermal hyperalgesia nor the desensitizing properties of olvanil, indicating a lack of involvement of CB1receptors. Conclusions: Olvanil is effective in reducing capsaicin-induced thermal hyperalgesia, probably via directly desensitizingTRPV1 channels in a CB 1 receptor-independent fashion. The results presented clearly support the potential for olvanil in the development of new topical analgesic preparations for treating chronic pain conditions while avoiding the unwanted side effects of capsaicin treatments

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man

Systematic review, network meta-analysis and exploratory cost-effectiveness model of randomized trials of minimally invasive techniques versus surgery for varicose veins

Background A Health Technology Assessment was conducted to evaluate the relative clinical effectiveness and cost-effectiveness of minimally invasive techniques (foam sclerotherapy (FS), endovenous laser ablation (EVLA) and radiofrequency ablation (RFA)) for managing varicose veins, in comparison with traditional surgery. Methods A systematic review of randomized clinical trials (RCTs) was undertaken to assess the effectiveness of minimally invasive techniques compared with other treatments, principally surgical stripping, in terms of recurrence of varicose veins, Venous Clinical Severity Score (VCSS), pain and quality of life. Network meta-analysis and exploratory cost-effectiveness modelling were performed. Results The literature search conducted in July 2011 identified 1453 unique citations: 31 RCTs (51 papers) satisfied the criteria for effectiveness review. Differences between treatments were negligible in terms of clinical outcomes, so the treatment with the lowest cost appears to be most cost-effective. Total FS costs were estimated to be lowest, and FS was marginally more effective than surgery. However, relative effectiveness was sensitive to the model time horizon. Threshold analysis indicated that EVLA and RFA might be considered cost-effective if their costs were similar to those for surgery. These findings are subject to various uncertainties, including the risk of bias present in the evidence base and variation in reported costs. Conclusion This assessment of currently available evidence suggests there is little to choose between surgery and the minimally invasive techniques in terms of efficacy or safety, so the relative cost of the treatments becomes one of the deciding factors. High-quality RCT evidence is needed to verify and further inform these findings

Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci.

Congenital imprinting disorders (IDs) are characterised by molecular changes affecting imprinted chromosomal regions and genes, i.e. genes that are expressed in a parent-of-origin specific manner. Recent years have seen a great expansion in the range of alterations in regulation, dosage or DNA sequence shown to disturb imprinted gene expression, and the correspondingly broad range of resultant clinical syndromes. At the same time, however, it has become clear that this diversity of IDs has common underlying principles, not only in shared molecular mechanisms, but also in interrelated clinical impacts upon growth, development and metabolism. Thus, detailed and systematic analysis of IDs can not only identify unifying principles of molecular epigenetics in health and disease, but also support personalisation of diagnosis and management for individual patients and families.All authors are members of the EUCID.net network, funded by COST (BM1208). TE is funded by the German Ministry of research and education (01GM1513B). GPdN is funded by I3SNS Program of the Spanish Ministry of Health (CP03/0064; SIVI 1395/09), Instituto de Salud Carlos III (PI13/00467) and Basque Department of Health (GV2014/111017).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13148-015-0143-

EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders: Silver–Russell and Beckwith–Wiedemann syndrome

Molecular genetic testing for the 11p15-associated imprinting disorders Silver–Russell and Beckwith–Wiedemann syndrome (SRS, BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. With the growing knowledge on the molecular basis of these disorders and the demand for molecular testing, it turned out that there is an urgent need for a standardized molecular diagnostic testing and reporting strategy. Based on the results from the first external pilot quality assessment schemes organized by the European Molecular Quality Network (EMQN) in 2014 and in context with activities of the European Network of Imprinting Disorders (EUCID.net) towards a consensus in diagnostics and management of SRS and BWS, best practice guidelines have now been developed. Members of institutions working in the field of SRS and BWS diagnostics were invited to comment, and in the light of their feedback amendments were made. The final document was ratified in the course of an EMQN best practice guideline meeting and is in accordance with the general SRS and BWS consensus guidelines, which are in preparation. These guidelines are based on the knowledge acquired from peer-reviewed and published data, as well as observations of the authors in their practice. However, these guidelines can only provide a snapshot of current knowledge at the time of manuscript submission and readers are advised to keep up with the literature

One step forward, two steps back?:the fading contours of (in)justice in competing discourses on climate migration

In recent debates on climate change and migration, the focus on the figure of ‘climate refugees’ (tainted by environmental determinism and a crude understanding of human mobility) has given ground to a broader conception of the climate–migration nexus. In particular, the idea that migration can represent a legitimate adaptation strategy has emerged strongly. This appears to be a positive development, marked by softer tones that de-securitise climate migration. However, political and normative implications of this evolution are still understudied. This article contributes to filling the gap by turning to both the ‘climate refugees’ and ‘migration as adaptation’ narratives, interrogating how and whether those competing narratives pose the question of (in)justice. Our analysis shows that the highly problematic ‘climate refugees’ narrative did (at least) channel justice claims and yielded the (illusory) possibility of identifying concrete rights claims and responsibilities. Read in relation to the growing mantra of resilience in climate policy and politics, the more recent narrative on ‘migration as adaptation’ appears to displace justice claims and inherent rights in favour of a depoliticised idea of adaptation that relies on the individual migrant's ability to compete in and benefit from labour markets. We warn that the removal of structural inequalities from the way in which the climate–migration nexus is understood can be seen as symptomatic of a shrinking of the conditions to posing the question of climate justice

Advanced nanoanalysis of a Hf-based high-<i>k</i> dielectric stack prior to activation

Analytical electron microscopy techniques are used to investigate elemental distributions across a high-&lt;i&gt;k&lt;/i&gt; dielectric stack with a metal gate. Electron energy-loss spectroscopy results from a Si(100)/SiO2/HfO2/TiN/a-Si gate stack confirm the presence of an oxide interfacial phase at the TiN/a-Si interface prior to activation of the stack