707-6 Amiodarone Decreases Ability of Baseline Ventricular Arrhythmia Severity to Predict Mortality

The Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT) entered 633 high risk patients (pts) with ejection fraction (EF)≤40%, PVCs/hr≥10 on 24 hour Holter recording and on active vasodilator therapy. Pts were randomized to amiodarone or placebo. Despite marked ventricular arrhythmia suppression, overall mortality was the same for amiodarone and placebo treated pts. An analysis to identify groups at risk based on frequency or severity of ventricular arrhythmia at baseline for both placebo and amiodarone is as follows:PlaceboAmiodaroneM1pM1pPVCs < 30/hr4%14%> 30/hr19%<0.00219%NS (0.47)PVCs < median*11%16%> median21%<0.000319%NS (0.54)High EF, Low PVC*11%13%High PVC13%NS14%NS (0.48)Low EF, Low PVC*14%17%)High PVC28%<0.0523%)NS (0.48)VT≤3 events/24hr13%16%≥421%<0.00320%NS (0.43)M1 = first year mortality*High, Low = >, <, median, EF (26%) & PVCs/hr (128)While increased arrhythmia severity predicted increased mortality on placebo, it did not in patients subsequently assigned to amiodarone treatment. Amiodarone appears to counter the effect of increased arrhythmia severity on mortality

Patterns in participation: Factors influencing parent attendance at two, centre-based early childhood interventions

Interventions training parents of at-risk children have received considerable empirical support but their effectiveness is undermined by low attendance rates. This research sought to clarify why parents, even with the best of intentions, fail to follow through to full participation in workshop programs; and to provide insight into ways to improve parental engagement. We examined participation in Parents as Partners, a school-based, early childhood intervention. Demographic and ongoing educational, social, emotional and behavioural data for 136 parent-child dyads were gathered from parents, teachers and children. Mitigation of a wide range of factors previously identified as barriers to attendance was also attempted. A post-intervention survey was conducted to examine parents’ insights into their attendance patterns. Overall, 91 parents attended and 44 failed to attend any workshops. Higher parent education and SEI, and better child language skills were good predictors of attendance (87%), but poor predictors of nonattendance (42%). Additionally, parent-child dyad profiles suggested that children of nonattending parents were more likely to benefit from workshop content than attenders’ children. Survey data suggested that attenders organised their schedules to facilitate follow-through but nonattenders were unable to do so. Family characteristics and practical reasons were central, interacting factors affecting attendance. Parental self-organisation appeared to moderate follow-through and to stem from lifestyle constraints related to lower SEI and parent education. This produced high nonattendance rates in parents of children who most needed support. It is urgent to discover to what extent innovative delivery platforms currently being explored (e.g., internet/social media) can improve parental engagement

Soundscape assessment of aircraft height and size

It is accepted knowledge that, for a given equivalent sound pressure level, sounds produced by planes are worse received from local communities than other sources related to transportation. Very little is known on the reasons for this special status, including any interactions that non-acoustical factors may have in listener assessments. Here we focus on one of such factors, the multisensory aspect of aircraft events. We propose a method to assess the visual impact of perceived aircraft height and size, beyond the objective increase in sound pressure level for a plane flying lower than another. We utilize a soundscape approach, based on acoustical indicators (dBs, LA, max, background sound pressure level) and social surveys: a combination of postal questionnaires (related to long-term exposure) and field interviews (related to the contextual perception), complementing well-established questions with others designed to capture new multisensory relationships. For the first time, we report how the perceived visual height of airplanes can be established using a combination of visual size, airplane size, reading distance, and airplane distance. Visual and acoustic assessments are complemented and contextualized by additional questions probing the subjective, objective, and descriptive assessments made by observers as well as how changes in airplane height over time may have influenced these perceptions. The flexibility of the proposed method allows a comparison of how participant reporting can vary across live viewing and memory recall conditions, allowing an examination of listeners' acoustic memory and expectations. The compresence of different assessment methods allows a comparison between the “objective” and the “perceptual” sphere and helps underscore the multisensory nature of observers' perceptual and emotive evaluations. In this study, we discuss pro and cons of our method, as assessed during a community survey conducted in the summer 2017 around Gatwick airport, and compare the different assessments of the community perception

Waterjet processes for coating removal

USBI and NASA have been testing and investigating the use of high pressure water for coating removal for approximately the past 12 years at the Automated TPS (Thermal Protection System - ablative materials used for thermal protection during ascent and descent of the solid rocket boosters) Removal Facility located in the Productivity Enhancement Complex at Marshall Space Flight Center. Originally the task was to develop and automate the removal process and transfer the technology to a production facility at Kennedy Space Center. Since that time more and more applications and support roles for the waterjet technology have been realized. The facility has become a vital part of development activities ongoing at MSFC. It supports the development of environmentally compliant insulations, sealants, and coatings. It also supports bonding programs, test motors, and pressure vessels. The most recent role of the cell is supporting Thiokol Corporation's solid rocket motor program in the development of waterjet degreasing and paint stripping methods. Currently vapor degreasing methods use 500,000 lbs. of ozone depleting chemicals per year. This paper describes the major cell equipment, test methods practiced, and coatings that have been removed

Detecting and tracing farmed salmon with natural geo-element otolith ‘fingerprint’ tags: developing and validating tag delivery techniques

Farmed fish escape and enter the environment with possible effects on wild populations. Attempts to reduce the incidence of escape could be assisted if individuals can be traced back to the point of escape, so that escape causes can be identified and technical standards improved. We tested if permanent marks could be created on the otoliths of salmon that could be detected throughout the lives of the fish. Marks were created by altering the natural ratios of the natural elements barium (Ba) and strontium (Sr) in the otolith. By combining several natural geo-elements, unique fingerprints can be created, which can act as codes that enable tracing of fish back to the point of escape. The marks are detected by laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS). We delivered marks to salmon in 4 different ways: 1) injecting female broodstock with geo-element markers prior to spawning so that the marks can be passed from the mother to all eggs in a clutch, with all larvae receiving a mark in the core of their otolith; 2) incorporating small amounts of geo-element markers into the vaccination serum for co-delivery of the marks into the fish along with the vaccine; 3) bathing eggs of salmon in geo-element solution immediately after fertilisation; and 4) bathing late stage yolk-sac larvae in an geo-element solution. All methods were successful in creating unique, permanent marks on the otoliths of salmon that could be detected throughout the lifetime of the fish. For all four delivery techniques, marking was 100% successful with Ba at concentrations as low as 0.001 μg. g-1 fish and for Sr at 1 μg. g-1 fish. Detection limits with the laser were set at 99.94%, so the techniques delivered a very high degree of accuracy. In all methods, we developed procedures that minimized marking and analysis costs, so that methods could be implemented at full-scale commercial application. After marking, fish were ongrown under standard commercial conditions to harvest size (approx. 4 kg). Marking methods had no effect on all standard production parameters, such as survival, growth, and the incidence of larval deformities compared to unmarked control fish. Further, the amounts of natural 2 strontium and barium used to create the marks are so small that they pose no problem for food safety, as they represent less than 0.1–1% of the amounts that naturally occur in salmon tissues. Our results indicate single marking with one of the techniques can create up to 63 unique fingerprint marks at low cost using Ba (0.0002–0.02 $US per mark) and Sr (0.46–0.82$US per mark). Double marking in different parts of the otolith using two of the different code delivery methods was also successful (e.g. maternal transfer and vaccination combined). This means 63 x 15 unique codes, or 1023 codes are possible, which is sufficient to provide a unique code for every site in the sea in Norway. We conclude that fingerprinting with natural geo-elements is feasible for commercial application. 94% of the salmon in Norway could be marked for as little as 0.02 $US per fish with a single marking method with traceability back to the top 63 producing companies. Double marking would enable more detailed tracing of every fish back to its site in the sea.Oppdrettslaks rømmer og kan påvirke de ville populasjonene. Antallet rømminger kunne vært redusert hvis den rømte fisken kunne vært sporet tilbake til rømningsstedet slik at årsaken til rømning kunne blitt identifisert. Vi testet om det er mulig å lage kjemiske merker på laksens ørestein som kan identifiseres gjennom hele livssyklusen. Disse merkene ble laget ved å endre forholdet mellom naturlige geoelementer (stabile isotoper av barium (Ba) og strontium (Sr)) i øresteinen. Ved å kombinere flere av disse naturlige geoelementene kan en lage unike ’fingeravtrykk/strekkoder’ som kan brukes for å spore en fisk tilbake til rømningsstedet. Merkene leses ved en teknikk hvor en brenner hull i øresteinen med laser og måler sammensetningen ved hjelp av massespektrometri. Merkene i øresteinen ble etablert ved hjelp av fire metoder: 1) ved å injisere morfisken med geoelementer i forkant av gytingen slik at disse kan overføres til alle eggene og at merket blir avsatt i øresteinens kjerne; 2) ved å tilsette små mengder av geoelementene i fiskens vaksine slik at fisken merkes ved vaksineringen; 3) ved å tilsette geoelementer i svellevannet som tilsettes rett etter befruktningen av eggene; 4) ved å bade plommesekkyngelen i en løsning med geoelementer. Ved alle metodene klarte vi å lage unike, permanente merker i øresteinen som kunne finnes og kjennes igjen gjennom hele fiskens livssyklus. Alle metodene ga 100 Etter merking ble fisken oppdrettet under standard oppdrettsbetingelser til slaktestørrelse (ca. 4 kg). Merkemetodene påvirket ingen produksjonsparametre som overlevelse, vekst eller innslag av deformiteter. Mengden naturlig strontium og barium som ble brukt er mindre enn 1 Våre resultater viser at en ved enkel merking med en av teknikkene kan lage opptil 63 unike ‘fingeravtrykk’ til en lav kostnad ved bruk av Ba (0,0002–0,02$US per merke) og Sr (0,46–0,82 $US per 3 merke). Dobbelmerking; dvs. å merke i ulike deler av øresteinen ved hjelp av to av metodene, var også mulig (for eksempel injeksjon av morfisk og vaksinering på parrstadiet). Dette betyr at en kan lage 63 x 15 = 1023 unike koder, nok til å gi hver lokalitet i Norge en unik kode. Vi konkluderer med at merking med naturlige geoelementer er en mulig løsning for å merke oppdrettsfisk. 94$US per fisk og med mulighet til å spore den tilbake til de 63 største produsentene. Dobbelmerking gir mulighet for sporing tilbake til lokalitet

Antisense oligonucleotide induced exon skipping and the dystrophin gene transcript: cocktails and chemistries

<p>Abstract</p> <p>Background</p> <p>Antisense oligonucleotides (AOs) can interfere with exon recognition and intron removal during pre-mRNA processing, and induce excision of a targeted exon from the mature gene transcript. AOs have been used <it>in vitro </it>and <it>in vivo </it>to redirect dystrophin pre-mRNA processing in human and animal cells. Targeted exon skipping of selected exons in the dystrophin gene transcript can remove nonsense or frame-shifting mutations that would otherwise have lead to Duchenne Muscular Dystrophy, the most common childhood form of muscle wasting.</p> <p>Results</p> <p>Although many dystrophin exons can be excised using a single AO, several exons require two motifs to be masked for efficient or specific exon skipping. Some AOs were inactive when applied individually, yet pronounced exon excision was induced in transfected cells when the AOs were used in select combinations, clearly indicating synergistic rather than cumulative effects on splicing. The necessity for AO cocktails to induce efficient exon removal was observed with 2 different chemistries, 2'-O-methyl modified bases on a phosphorothioate backbone and phosphorodiamidate morpholino oligomers. Similarly, other trends in exon skipping, as a consequence of 2'-O-methyl AO action, such as removal of additional flanking exons or variations in exon skipping efficiency with overlapping AOs, were also seen when the corresponding sequences were prepared as phosphorodiamidate morpholino oligomers.</p> <p>Conclusion</p> <p>The combination of 2 AOs, directed at appropriate motifs in target exons was found to induce very efficient targeted exon skipping during processing of the dystrophin pre-mRNA. This combinatorial effect is clearly synergistic and is not influenced by the chemistry of the AOs used to induce exon excision. A hierarchy in exon skipping efficiency, observed with overlapping AOs composed of 2'-O-methyl modified bases, was also observed when these same sequences were evaluated as phosphorodiamidate morpholino oligomers, indicating design parameters established with one chemistry may be applied to the other.</p

The Educational Progress of Looked After Children in England:Linking Care and Educational Data

First major study in England to explore the relationship between educational outcomes, young people’s care histories and individual characteristics. It focused on the reasons for the low educational outcomes of young people in care (looked after) in secondary schools in England

Biofilm Formation by Listeria monocytogenes 15G01, a Persistent Isolate from a Seafood-Processing Plant, Is Influenced by Inactivation of Multiple Genes Belonging to Different Functional Groups

Listeria monocytogenes is a ubiquitous foodborne pathogen that results in a high rate of mortality in sensitive and immunocompromised people. Contamination of food with L. monocytogenes is thought to occur during food processing, most often as a result of the pathogen producing a biofilm that persists in the environment and acting as the source for subsequent dispersal of cells onto food. A survey of seafoodprocessing plants in New Zealand identified the persistent strain 15G01, which has a high capacity to form biofilms. In this study, a transposon library of L. monocytogenes 15G01 was screened for mutants with altered biofilm formation, assessed by a crystal violet assay, to identify genes involved in biofilm formation. This screen identified 36 transposants that showed a significant change in biofilm formation compared to the wild type. The insertion sites were in 27 genes, 20 of which led to decreased biofilm formation and seven to an increase. Two insertions were in intergenic regions. Annotation of the genes suggested that they are involved in diverse cellular processes, including stress response, autolysis, transporter systems, and cell wall/membrane synthesis. Analysis of the biofilms produced by the transposants using scanning electron microscopy and fluorescence microscopy showed notable differences in the structure of the biofilms compared to the wild type. In particular, inactivation of uvrB and mltD produced coccoid-shaped cells and elongated cells in long chains, respectively, and the mgtB mutant produced a unique biofilm with a sandwich structure which was reversed to the wild-type level upon magnesium addition. The mltD transposant was successfully complemented with the wild-type gene, whereas the phenotypes were not or only partially restored for the remaining mutants. IMPORTANCE The major source of contamination of food with Listeria monocytogenes is thought to be due to biofilm formation and/or persistence in food-processing plants. By establishing as a biofilm, L. monocytogenes cells become harder to eradicate due to their increased resistance to environmental threats. Understanding the genes involved in biofilm formation and their influence on biofilm structure will help identify new ways to eliminate harmful biofilms in food processing environments. To date, multiple genes have been identified as being involved in biofilm formation by L. monocytogenes; however, the exact mechanism remains unclear. This study identified four genes associated with biofilm formation by a persistent strain. Extensive microscopic analysis illustrated the effect of the disruption of mgtB, clsA, uvrB, and mltD and the influence of magnesium on the biofilm structure. The results strongly suggest an involvement in biofilm formation for the four genes and provide a basis for further studies to analyze gene regulation to assess the specific role of these biofilm-associated genes.Peer reviewe

Development of the Supply Chain Optimization and Planning for the Environment (SCOPE) tool - applied to solar energy

A supply-chain decision tool is outlined that will assess the life-cycle greenhouse gases and energy demand of solar energy technology using a hybrid LCA structure. Energy and greenhouse gas metrics appropriate for the climate change mitigation goals of solar energy are discussed. Applying this methodology to SolFocus Inc. concentrator systems, preliminary results indicate that the energy payback time of SolFocus Panels can vary from 0.6 to 5 years depending on manufacturing locations. The greenhouse gas payback time, a new metric for energy technologies, varies from 1.1 to 64 years depending on the same factors indicating that greenhouse gas metrics are more sensitive to installation and supply chain decisions than energy metrics