Upper tropospheric ozone production from lightning NOx-impacted convection: Smoke ingestion case study from the DC3 campaign

©2015. American Geophysical Union. All Rights Reserved. As part of the Deep Convective Cloud and Chemistry (DC3) experiment, the National Science Foundation/National Center for Atmospheric Research (NCAR) Gulfstream-V (GV) and NASA DC-8 research aircraft probed the chemical composition of the inflow and outflow of two convective storms (north storm, NS, south storm, SS) originating in the Colorado region on 22 June 2012, a time when the High Park wildfire was active in the area. A wide range of trace species were measured on board both aircraft including biomass burning (BB) tracers hydrogen cyanide (HCN) and acetonitrile (ACN). Acrolein, a much shorter lived tracer for BB, was also quantified on the GV. The data demonstrated that the NS had ingested fresh smoke from the High Park fire and as a consequence had a higher VOC OH reactivity than the SS. The SS lofted aged fire tracers along with other boundary layer ozone precursors and was more impacted by lightning NOx (LNOx) than the NS. The NCAR master mechanism box model was initialized with measurements made in the outflow of the two storms. The NS and SS were predicted to produce 11 and 14ppbv of O3, respectively, downwind of the storm over 2days. Sensitivity tests revealed that the ozone production potential of the SS was highly dependent on LNOx. Normalized excess mixing ratios, ΔX/ΔCO, for HCN and ACN were determined in both the fire plume and the storm outflow and found to be 7.0±0.5 and 2.3±0.5pptvppbv-1, respectively, and 1.4±0.3pptvppbv-1 for acrolein in the outflow only

A multidisciplinary systematic literature review on frailty: Overview of the methodology used by the Canadian Initiative on Frailty and Aging

<p>Abstract</p> <p>Background</p> <p>Over the past two decades, there has been a substantial growth in the body of literature on frailty in older persons. However, there is no consensus on its definition or the criteria used to identify frailty. In response to this lack of consensus, the Canadian Initiative on Frailty and Aging carried out a set of systematic reviews of the literature in ten areas of frailty research: biological basis; social basis; prevalence; risk factors; impact; identification; prevention and management; environment and technology; health services; health and social policy. This paper describes the methodology that was developed for the systematic reviews.</p> <p>Methods</p> <p>A Central Coordination Group (CCG) was responsible for developing the methodology. This involved the development of search strategies and keywords, article selection processes, quality assessment tools, and guidelines for the synthesis of results. Each review was conducted by two experts in the content area, with the assistance of methodologists and statisticians from the CCG.</p> <p>Results</p> <p>Conducting a series of systematic literature reviews involving a range of disciplines on a concept that does not have a universally accepted definition posed several conceptual and methodological challenges. The most important conceptual challenge was determining what would qualify as literature on frailty. The methodological challenges arose from our goal of structuring a consistent methodology for reviewing literature from diverse fields of research. At the outset, certain methodological guidelines were deemed essential to ensure the validity of all the reviews. Nevertheless, it was equally important to permit flexibility in the application of the proposed methodology to capture the essence of frailty research within the given fields.</p> <p>Conclusion</p> <p>The results of these reviews allowed us to establish the status of current knowledge on frailty and promote collaboration between disciplines. Conducting systematic literature reviews in health science that involve multiple disciplines is a mechanism to facilitate interdisciplinary collaboration and a more integrated understanding of health. This initiative highlighted the need for further methodological development in the performance of multidisciplinary systematic reviews.</p

An Ethical Façade? Medical Students' Miscomprehensions of Substituted Judgment

Background: We studied how well first-year medical students understand and apply the concept of substituted judgment, following a course on clinical ethics. Method: Students submitted essays on one of three ethically controversial scenarios presented in class. One scenario involved a patient who had lost decisional capacity. Through an iterative process of textual analysis, the essays were studied and coded for patterns in the ways students misunderstood or misapplied the principle of substituted judgment. Results: Students correctly articulated course principles regarding patient autonomy, substituted judgment, and nonimposition of physician values. However, students showed misunderstanding by giving doctors the responsibility of balancing the interests of the patient against the interests of the family, by stating doctors and surrogates should be guided primarily by a best-interest standard, and by suggesting that patient autonomy becomes the guiding principle only when patients can no longer express their wishes. Conclusion: Students did not appear to internalize or correctly apply the substituted judgment standard, even though they could describe it accurately. This suggests the substituted judgment standard may run counter to students ’ moral intuitions

A Plasma Survey Using 38 PfEMP1 Domains Reveals Frequent Recognition of the Plasmodium falciparum Antigen VAR2CSA among Young Tanzanian Children

PfEMP1 proteins comprise a family of variant antigens that appear on the surface of P. falciparum-infected erythrocytes and bind to multiple host receptors. Using a mammalian expression system and BioPlex technology, we developed an array of 24 protein constructs representing 38 PfEMP1 domains for high throughput analyses of receptor binding as well as total and functional antibody responses. We analyzed the reactivity of 561 plasma samples from 378 young Tanzanian children followed up to maximum 192 weeks of life in a longitudinal birth cohort. Surprisingly, reactivity to the DBL5 domain of VAR2CSA, a pregnancy malaria vaccine candidate, was most common, and the prevalence of reactivity was stable throughout early childhood. Reactivity to all other PfEMP1 constructs increased with age. Antibodies to the DBL2βC2PF11_0521 domain, measured as plasma reactivity or plasma inhibition of ICAM1 binding, predicted reduced risk of hospitalization for severe or moderately severe malaria. These data suggest a role for VAR2CSA in childhood malaria and implicate DBL2βC2PF11_0521 in protective immunity

Infrared light excites cells by changing their electrical capacitance

Optical stimulation has enabled important advances in the study of brain function and other biological processes, and holds promise for medical applications ranging from hearing restoration to cardiac pace making. In particular, pulsed laser stimulation using infrared wavelengths >1.5 μm has therapeutic potential based on its ability to directly stimulate nerves and muscles without any genetic or chemical pre-treatment. However, the mechanism of infrared stimulation has been a mystery, hindering its path to the clinic. Here we show that infrared light excites cells through a novel, highly general electrostatic mechanism. Infrared pulses are absorbed by water, producing a rapid local increase in temperature. This heating reversibly alters the electrical capacitance of the plasma membrane, depolarizing the target cell. This mechanism is fully reversible and requires only the most basic properties of cell membranes. Our findings underscore the generality of pulsed infrared stimulation and its medical potential

High Throughput Functional Assays of the Variant Antigen PfEMP1 Reveal a Single Domain in the 3D7 Plasmodium falciparum Genome that Binds ICAM1 with High Affinity and Is Targeted by Naturally Acquired Neutralizing Antibodies

Plasmodium falciparum–infected erythrocytes bind endothelial receptors to sequester in vascular beds, and binding to ICAM1 has been implicated in cerebral malaria. Binding to ICAM1 may be mediated by the variant surface antigen family PfEMP1: for example, 6 of 21 DBLβC2 domains from the IT4 strain PfEMP1 repertoire were shown to bind ICAM1, and the PfEMP1 containing these 6 domains are all classified as Group B or C type. In this study, we surveyed binding of ICAM1 to 16 DBLβC2 domains of the 3D7 strain PfEMP1 repertoire, using a high throughput Bioplex assay format. Only one DBL2βC2 domain from the Group A PfEMP1 PF11_0521 showed strong specific binding. Among these 16 domains, DBL2βC2PF11_0521 best preserved the residues previously identified as conserved in ICAM1-binding versus non-binding domains. Our analyses further highlighted the potential role of conserved residues within predominantly non-conserved flexible loops in adhesion, and, therefore, as targets for intervention. Our studies also suggest that the structural/functional DBLβC2 domain involved in ICAM1 binding includes about 80 amino acid residues upstream of the previously suggested DBLβC2 domain. DBL2βC2PF11_0521 binding to ICAM1 was inhibited by immune sera from east Africa but not by control US sera. Neutralizing antibodies were uncommon in children but common in immune adults from east Africa. Inhibition of binding was much more efficient than reversal of binding, indicating a strong interaction between DBL2βC2PF11_0521 and ICAM1. Our high throughput approach will significantly accelerate studies of PfEMP1 binding domains and protective antibody responses

Several domains from VAR2CSA can induce Plasmodium falciparum adhesion-blocking antibodies

<p>Abstract</p> <p>Background</p> <p>Malaria caused by <it>Plasmodium falciparum </it>can result in several different syndromes with severe clinical consequences for the about 200 million individuals infected each year. During pregnancy, women living in endemic areas become susceptible to malaria due to lack of antibodies against a unique <it>P. falciparum </it>membrane protein, named VAR2CSA. This antigen is not expressed in childhood infections, since it binds chondroitin sulphate A (CSA) expressed on the intervillous space in the placenta. A vaccine appears possible because women acquire protective antibodies hindering sequestration in the placenta as a function of parity. A challenge for vaccine development is to design small constructs of this large antigen, which can induce broadly protective antibodies. It has previously been shown that one domain of VAR2CSA, DBL4-FCR3, induces parasite adhesion-blocking antibodies. In this study, it is demonstrated that other domains of VAR2CSA also can induce antibodies with inhibitory activity.</p> <p>Methods</p> <p>All VAR2CSA domains from the 3D7 and HB3 parasites were produced in <it>Baculovirus</it>-transfected insect cells. Groups of three rats per protein were immunized and anti-sera were tested for surface reactivity against infected erythrocytes expressing FCR3 VAR2CSA and for the ability to inhibit FCR3CSA parasite adhesion to CSA. The fine specificity of the immune sera was analysed by VAR2CSA peptide arrays.</p> <p>Results</p> <p>Inhibitory antibodies were induced by immunization with DBL3-HB3 T1 and DBL1-3D7. However, unlike the previously characterised DBL4-FCR3 response the inhibitory response against DBL1-3D7 and DBL3-HB3 T1 was poorly reproduced in the second rounds of immunizations.</p> <p>Conclusion</p> <p>It is possible to induce parasite adhesion-blocking antibodies when immunizing with a number of different VAR2CSA domains. This indicates that the CSA binding site in VAR2CSA is comprised of epitopes from different domains.</p

A pilot study combining individual-based smoking cessation counseling, pharmacotherapy, and dental hygiene intervention

BACKGROUND: Dentists are in a unique position to advise smokers to quit by providing effective counseling on the various aspects of tobacco-induced diseases. The present study assessed the feasibility and acceptability of integrating dentists in a medical smoking cessation intervention. METHODS: Smokers willing to quit underwent an 8-week smoking cessation intervention combining individual-based counseling and nicotine replacement therapy and/or bupropion, provided by a general internist. In addition, a dentist performed a dental exam, followed by an oral hygiene treatment and gave information about chronic effects of smoking on oral health. Outcomes were acceptability, global satisfaction of the dentist's intervention, and smoking abstinence at 6-month. RESULTS: 39 adult smokers were included, and 27 (69%) completed the study. Global acceptability of the dental intervention was very high (94% yes, 6% mostly yes). Annoyances at the dental exam were described as acceptable by participants (61% yes, 23% mostly yes, 6%, mostly no, 10% no). Participants provided very positive qualitative comments about the dentist counseling, the oral exam, and the resulting motivational effect, emphasizing the feeling of oral cleanliness and health that encouraged smoking abstinence. At the end of the intervention (week 8), 17 (44%) participants reported smoking abstinence. After 6 months, 6 (15%, 95% CI 3.5 to 27.2) reported a confirmed continuous smoking abstinence. DISCUSSION: We explored a new multi-disciplinary approach to smoking cessation, which included medical and dental interventions. Despite the small sample size and non-controlled study design, the observed rate was similar to that found in standard medical care. In terms of acceptability and feasibility, our results support further investigations in this field. TRIAL REGISTRATION NUMBER: ISRCTN67470159

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

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