Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine : randomized double-blind phase II evaluation of safety and immunogenicity

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril(®), Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE virus strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

A roadside survey of unlicensed driving in Queensland

Unlicensed driving remains a serious problem in many jurisdictions, and while it does not play a direct causative role in road crashes, it undermines driver licensing systems and is linked to other high risk driving behaviours. Roadside licence check surveys represent the most direct means of estimating the prevalence of unlicensed driving. The current study involved the Queensland Police Service (QPS) checking the licences of 3,112 drivers intercepted at random breath testing operations across Queensland between February and April 2010. Data was matched with official licensing records from Transport and Main Roads (TMR) via the drivers’ licence number. In total, 2,914 (93.6%) records were matched, with the majority of the 198 unmatched cases representing international or interstate licence holders (n = 156), leaving 42 unknown cases. Among the drivers intercepted at the roadside, 20 (0.6%) were identified as being unlicensed at the time, while a further 11 (0.4%) were driving unaccompanied on a Learner Licence. However, the examination of TMR licensing records revealed that an additional 9 individuals (0.3%) had a current licence sanction but were not identified as unlicensed by QPS. Thus, in total 29 of the drivers were unlicensed at the time, representing 0.9% of all the drivers intercepted and 1% of those for whom their licence records could be checked. This is considerably lower than the involvement of unlicensed drivers in fatal and serious injury crashes in Queensland, which is consistent with other research confirming the increased crash risk of the group. However, the number of unmatched records suggest that it is possible the on-road survey may have under-estimated the prevalence of unlicensed driving, so further development of the survey method is recommended.

Infrared and Raman spectroscopic characterization of the silicate mineral olmiite CaMn2+[SiO3(OH)](OH) : implications for the molecular structure

We have studied the mineral olmiite CaMn\[SiO3(OH)](OH) which forms a series with its calcium analogue poldevaartite CaCa\[SiO3(OH)](OH) using a range of techniques including scanning electron microscopy, thermogravimetric analysis , Raman and infrared spectroscopy. Chemical analysis shows the mineral is pure and contains only calcium and manganese in the formula. Thermogravimetric analysis proves the mineral decomposes at 502°C with a mass loss of 8.8% compared with the theoretical mass loss of 8.737%. A strong Raman band at 853 cm-1 is assigned to the SiO stretching vibration of the SiO3(OH) units. Two Raman bands at 914 and 953 cm-1 are attributed to the antisymmetric vibrations.Two intense Raman bands observed at 3511 and 3550 cm-1 are assigned to the OH stretching vibration of the SiO3(OH) units. The observation of multiple OH bands supports the concept of the non-equivalence of the OH units. Vibrational spectroscopy enables a detailed assessment of the molecular structure of olmiite.

SRL 172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer : phase III results

Background: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. Results: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). Conclusion: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times. © 2004 European Society for Medical Oncology.

An extracellular signal-regulated kinase 2 survival pathway mediates resistance of human mesothelioma cells to asbestos-induced injury

We hypothesized that normal human mesothelial cells acquire resistance to asbestos-induced toxicity via induction of one or more epidermal growth factor receptor (EGFR) - linked survival pathways (phosphoinositol-3-kinase/AKT/ mammalian target of rapamycin and extracellular signal - regulated kinase [ERK] 1/2) during simian virus 40 (SV40) transformation and carcinogenesis. Both isolated HKNM-2 mesothelial cells and a telomerase-immortalized mesothelial line (LP9/TERT-1) were more sensitive to crocidolite asbestos toxicity than an SV40 Tag-immortalized mesothelial line (MET5A) and malignant mesothelioma cell lines (HMESO and PPM Mill). Whereas increases in phosphorylation of AKT (pAKT) were observed in MET5A cells in response to asbestos, LP9/TERT-1 cells exhibited dose-related decreases in pAKT levels. Pretreatment with an EGFR phosphorylation or mitogen-activated protein kinase kinase 1/2 inhibitor abrogated asbestos-induced phosphorylated ERK (pERK) 1/2 levels in both LP9/TERT-1 and MET5A cells as well as increases in pAKT levels in MET5A cells. Transient transfection of small interfering RNAs targeting ERK1, ERK2, or AKT revealed that ERK1/2 pathways were involved in cell death by asbestos in both cell lines. Asbestos-resistant HMESO or PPM Mill cells with high endogenous levels of ERKs or AKT did not show dose-responsive increases in pERK1/ERK1, pERK2/ERK2, or pAKT/AKT levels by asbestos. However, small hairpin ERK2 stable cell lines created from both malignant mesothelioma lines were more sensitive to asbestos toxicity than shERK1 and shControl lines, and exhibited unique, tumor-specific changes in endogenous cell death - related gene expression. Our results suggest that EGFR phosphorylation is causally linkedto pERK and pAKT activation by asbestos in normal and SV40 Tag - immortalized human mesothelial cells. They also indicate that ERK2 plays a role in modulating asbestos toxicity by regulating genes critical to cell injury and survival that are differentially expressed in human mesotheliomas.

The M(r) 43K major capsid protein of rice ragged stunt oryzavirus is a post-translationally processed product of a M(r) 67 348 polypeptide encoded by genome segment 8

The nucleotide sequence of DNA complementary to rice ragged stunt oryzavirus (RRSV) genome segment 8 (S8) of an isolate from Thailand was determined. RRSV S8 is 1 914 bp in size and contains a single large open reading frame (ORF) spanning nucleotides 23 to 1 810 which is capable of encoding a protein of M(r) 67 348. The N-terminal amino acid sequence of a ~43K virion polypeptide matched to that inferred for an internal region of the S8 coding sequence. These data suggest that the 43K protein is encoded by S8 and is derived by a proteolytic cleavage. Predicted polypeptide sizes from this possible cleavage of S8 protein are 26K and 42K. Polyclonal antibodies raised against a maltose binding protein (MBP)-S8 fusion polypeptide (expressed in Escherichia coli) recognised four RRSV particle associated polypeptides of M(r) 67K, 46K, 43K and 26K and all except the 26K polypeptide were also highly immunoreactive to polyclonal antibodies raised against purified RRSV particles. Cleavage of the MBP-S8 fusion polypeptide with protease Factor X produced the expected 40K MBP and two polypeptides of apparent M(r) 46K and 26K. Antibodies to purified RRSV particles reacted strongly with the intact fusion protein and the 46K cleavage product but weakly to the 26K product. Furthermore, in vitro transcription and translation of the S8 coding region revealed a post-translational self cleavage of the 67K polypeptide to 46K and 26K products. These data indicate that S8 encodes a structural polypeptide, the majority of which is auto- catalytically cleaved to 26K and 46K proteins. The data also suggest that the 26K protein is the self cleaving protease and that the 46K product is further processed or undergoes stable conformational changes to a ~43K major capsid protein.

Slicing big data - Twitter, gambling and time sensitive information

Big Data presents many challenges related to volume, whether one is interested in studying past datasets or, even more problematically, attempting to work with live streams of data. The most obvious challenge, in a ‘noisy’ environment such as contemporary social media, is to collect the pertinent information; be that information for a specific study, tweets which can inform emergency services or other responders to an ongoing crisis, or give an advantage to those involved in prediction markets. Often, such a process is iterative, with keywords and hashtags changing with the passage of time, and both collection and analytic methodologies need to be continually adapted to respond to this changing information. While many of the data sets collected and analyzed are preformed, that is they are built around a particular keyword, hashtag, or set of authors, they still contain a large volume of information, much of which is unnecessary for the current purpose and/or potentially useful for future projects. Accordingly, this panel considers methods for separating and combining data to optimize big data research and report findings to stakeholders. The first paper considers possible coding mechanisms for incoming tweets during a crisis, taking a large stream of incoming tweets and selecting which of those need to be immediately placed in front of responders, for manual filtering and possible action. The paper suggests two solutions for this, content analysis and user profiling. In the former case, aspects of the tweet are assigned a score to assess its likely relationship to the topic at hand, and the urgency of the information, whilst the latter attempts to identify those users who are either serving as amplifiers of information or are known as an authoritative source. Through these techniques, the information contained in a large dataset could be filtered down to match the expected capacity of emergency responders, and knowledge as to the core keywords or hashtags relating to the current event is constantly refined for future data collection. The second paper is also concerned with identifying significant tweets, but in this case tweets relevant to particular prediction market; tennis betting. As increasing numbers of professional sports men and women create Twitter accounts to communicate with their fans, information is being shared regarding injuries, form and emotions which have the potential to impact on future results. As has already been demonstrated with leading US sports, such information is extremely valuable. Tennis, as with American Football (NFL) and Baseball (MLB) has paid subscription services which manually filter incoming news sources, including tweets, for information valuable to gamblers, gambling operators, and fantasy sports players. However, whilst such services are still niche operations, much of the value of information is lost by the time it reaches one of these services. The paper thus considers how information could be filtered from twitter user lists and hash tag or keyword monitoring, assessing the value of the source, information, and the prediction markets to which it may relate. The third paper examines methods for collecting Twitter data and following changes in an ongoing, dynamic social movement, such as the Occupy Wall Street movement. It involves the development of technical infrastructure to collect and make the tweets available for exploration and analysis. A strategy to respond to changes in the social movement is also required or the resulting tweets will only reflect the discussions and strategies the movement used at the time the keyword list is created — in a way, keyword creation is part strategy and part art. In this paper we describe strategies for the creation of a social media archive, specifically tweets related to the Occupy Wall Street movement, and methods for continuing to adapt data collection strategies as the movement’s presence in Twitter changes over time. We also discuss the opportunities and methods to extract data smaller slices of data from an archive of social media data to support a multitude of research projects in multiple fields of study. The common theme amongst these papers is that of constructing a data set, filtering it for a specific purpose, and then using the resulting information to aid in future data collection. The intention is that through the papers presented, and subsequent discussion, the panel will inform the wider research community not only on the objectives and limitations of data collection, live analytics, and filtering, but also on current and in-development methodologies that could be adopted by those working with such datasets, and how such approaches could be customized depending on the project stakeholders.

Histories of user-generated content : between formal and informal media economies

Debates about user-generated content (UGC) often depend on a contrast with its normative opposite, the professionally produced content that is supported and sustained by commercial media businesses or public organisations. UGC is seen to appear within or in opposition to professional media, often as a disruptive, creative, change-making force. Our suggestion is to position UGC not in opposition to professional or "producer media", or in hybridised forms of subjective combination with it (the so-called "pro-sumer" or "pro-am" system), but in relation to different criteria, namely the formal and informal elements in media industries. In this article, we set out a framework for the comparative and historical analysis of UGC systems and their relations with other formal and informal media activity, illustrated with examples ranging from games to talkback radio. We also consider the policy implications that emerge from a historicised reading of UGC as a recurring dynamic within media industries, rather than a manifestation of consumer agency specific to digital cultures.

Negative-ion photoelectron spectroscopy, gas-phase acidity, and thermochemistry of the peroxyl radicals CH3OO and CH3CH2OO

Methyl, methyl-d(3), and ethyl hydroperoxide anions (CH3OO-, CD3OO-, and CH3CH2OO-) have been prepared by deprotonation of their respective hydroperoxides in a stream of helium buffer, gas. Photodetachment with 364 nm (3.408 eV) radiation was used to measure the adiabatic electron affinities: EA[CH3OO, (X) over tilde (2)A"] = 1.161 +/- 0.005 eV, EA[CD3OO, (X) over tilde (2)A"] = 1.154 +/- 0.004 eV, and EA[CH3CH2OO, (X) over tilde (2)A"] = 1.186 +/- 0.004 eV. The photoelectron spectra yield values for the term energies: DeltaE((X) over tilde 2A"-(A) over tilde 2A')[CH3OO] = 0.914 +/- 0.005 eV, DeltaE((X) over tilde (2)A"-(A) over tilde 2A') [CD3OO] = 0.913 +/- 0.004 eV, and DeltaE((X) over tilde (2)A"-(A) over tilde (2)A')[CH3CH2OO] = 0.938 +/- 0.004 eV. A localized RO-O stretching mode was observed near 1100 cm(-1) for the ground state of all three radicals, and low-frequency R-O-O bending modes are also reported. Proton-transfer kinetics of the hydroperoxides have been measured in a tandem flowing afterglow-selected ion flow tube k(FA-SIFT) to determine the gas-phase acidity of the parent hydroperoxides: Delta (acid)G(298)(CH3OOH) = 367.6 +/- 0.7 kcal mol(-1), Delta (acid)G(298)(CD3OOH) = 367.9 +/- 0.9 kcal mol(-1), and Delta (acid)G(298)(CH3CH2OOH) = 363.9 +/- 2.0 kcal mol(-1). From these acidities we have derived the enthalpies of deprotonation: Delta H-acid(298)(CH3OOH) = 374.6 +/- 1.0 kcal mol(-1), Delta H-acid(298)(CD3OOH) = 374.9 +/- 1.1 kcal mol(-1), and Delta H-acid(298)(CH2CH3OOH) = 371.0 +/- 2.2 kcal mol(-1). Use of the negative-ion acidity/EA cycle provides the ROO-H bond enthalpies: DH298(CH3OO-H) 87.8 +/- 1.0 kcal mol(-1), DH298(CD3OO-H) = 87.9 +/- 1.1 kcal mol(-1), and DH298(CH3CH2OO-H) = 84.8 +/- 2.2 kcal mol(-1). We review the thermochemistry of the peroxyl radicals, CH3OO and CH3CH2OO. Using experimental bond enthalpies, DH298(ROO-H), and CBS/APNO ab initio electronic structure calculations for the energies of the corresponding hydroperoxides, we derive the heats of formation of the peroxyl radicals. The "electron affinity/acidity/CBS" cycle yields Delta H-f(298)[CH3OO] = 4.8 +/- 1.2 kcal mol(-1) and Delta H-f(298)[CH3CH2OO] = -6.8 +/- 2.3 kcal mol(-1).

The future Australian paramedic workforce : a snapshot of undergraduate paramedic students

Objective Describe the demographics of undergraduate paramedic students enrolled at a major Queensland University and explore the potential impact of demographic change in the paramedic workforce of the future. Method A retrospective, descriptive analysis of de-identified, routinely collected administrative data on students enrolled in the paramedic undergraduate degree program at Queensland University of Technology was undertaken for the period 2005-2013. Quantitative data were examined using the Statistical Package for Social Science version 21. Results A total of 914 students had commenced the paramedic degree since 2005, of whom slightly more than a third (33.4%; SD 9.5%) were enrolled in the double degree with nursing beginning from 2009. Half of the student cohort (52.1%;, SD 4.8%) were female, with the majority (82.9%;, SD 3.4) aged under 25 years old. Most (45.2%;, SD 13) of the student admissions were for graduate entry [i.e. prior tertiary education had been completed], while secondary education entry represented 35.9% (SD 14.9%). Conclusion By contrasting the results of our study to the most recent demographic data of the Australian paramedic workforce, a significant difference in the demographic characteristics of the current and future paramedic workforce is noted. Due to these differences, the need for increased flexibility in employment arrangements should be anticipated. This presentation will explore these characteristics and provide a complementary evidence base on which workforce planning within ambulance services can be conducted.

Identifying weak linear features with the "coalescing shortest path image transform"

The detection of line-like features in images finds many applications in microanalysis. Actin fibers, microtubules, neurites, pilis, DNA, and other biological structures all come up as tenuous curved lines in microscopy images. A reliable tracing method that preserves the integrity and details of these structures is particularly important for quantitative analyses. We have developed a new image transform called the "Coalescing Shortest Path Image Transform" with very encouraging properties. Our scheme efficiently combines information from an extensive collection of shortest paths in the image to delineate even very weak linear features. © Copyright Microscopy Society of America 2011.