Fasting increases serum bilirubin levels in clinically normal, healthy males but not females : a retrospective study from phase I clinical trial participants

Aim: To examine if fasting affects serum bilirubin levels in clinical healthy males and females. Methods: We utilised retrospective data from phase 1 clinical trials where blood was collected in either a fed or fasting state at screening and pre-dosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n = 105) or females (n = 30) aged 18 to 48 inclusive who participated in a phase 1 clinical trial in 2012 or 2013. Results: We found a statistically significant increase in total serum bilirubin levels in fasting males as compared to non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females. Conclusions: The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.

Inhibition of homogenous formation of calcium carbonate by poly (acrylic acid). The effect of molar mass and end-group functionality

The ability of poly(acrylic acid) (PAA) with different end groups and molar masses prepared by Atom Transfer Radical Polymerization (ATRP) to inhibit the formation of calcium carbonate scale at low and elevated temperatures was investigated. Inhibition of CaCO3 deposition was affected by the hydrophobicity of the end groups of PAA, with the greatest inhibition seen for PAA with hydrophobic end groups of moderate size (6–10 carbons). The morphologies of CaCO3 crystals were significantly distorted in the presence of these PAAs. The smallest morphological change was in the presence of PAA with long hydrophobic end groups (16 carbons) and the relative inhibition observed for all species were in the same order at 30 °C and 100 °C. As well as distorting morphologies, the scale inhibitors appeared to stabilize the less thermodynamically favorable polymorph, vaterite, to a degree proportional to their ability to inhibit precipitation.

Investigation of brain derived neurotrophic factor (BDNF) gene variants in migraine

A number of observations have suggested that brain derived neurotrophic factor (BDNF) plays a role in migraine pathophysiology. This study investigates whether variants in the BDNF gene are associated with migraine in an Australian case-control population. Background. Brain derived neurotrophic factor (BDNF) has an important role in neural growth, development and survival in the central nervous system and is an important modulator of central and peripheral pain responses. Variants in BDNF, in particular the functional Val66Met polymorphism (rs6265), have been found to be associated with a number of psychiatric disorders, cognitive function and obesity. As BDNF has been found to be differentially expressed in a number of aspects related to migraine, we tested for association between single nucleotide polymorphisms (SNPs) in BDNF and migraine. Methods. Five SNPs in the BDNF locus (rs1519480, rs6265, rs712507, rs2049046 and rs12273363) were genotyped initially in a cohort of 277 migraine cases, including 172 diagnosed with migraine with aura (MA) and 105 with migraine without aura (MO), and 277 age- and sex-matched controls. Three of these SNPs (rs6265, rs2049046 and rs12273363) were subsequently genotyped in a second cohort of 580 migraineurs, including 473 diagnosed with MA and 105 with O, and 580 matched controls. Results. – BDNF SNPs rs1519480, rs6265, rs712507 and rs12273363 were not significantly associated with migraine. However, rs2049046 showed a significant association with migraine, and in particular, MA in the first cohort. In the second cohort, although an increase in the rs2049046 T-allele frequency was observed in migraine cases, and in both MA and MO subgroups, it was not significantly different from controls. Analysis of data combined from both cohorts for rs2049046 showed significant differences in the genotypic and allelic distributions for this marker in both migraine and the MA sub-group. Conclusion. This study confirmed previous studies that the functional BDNF SNP rs6265 (Val66Met) is not associated with migraine. However, we found that rs2049046, which resides at the 5’ end of 3 one the BDNF transcripts, may be associated with migraine, suggesting that further investigations of this SNP may be warranted.

Outdoor flight testing of a pole inspection UAV incorporating high-speed vision

We present a pole inspection system for outdoor environments comprising a high-speed camera on a vertical take-off and landing (VTOL) aerial platform. The pole inspection task requires a vehicle to fly close to a structure while maintaining a fixed stand-off distance from it. Typical GPS errors make GPS-based navigation unsuitable for this task however. When flying outdoors a vehicle is also affected by aerodynamics disturbances such as wind gusts, so the onboard controller must be robust to these disturbances in order to maintain the stand-off distance. Two problems must therefor be addressed: fast and accurate state estimation without GPS, and the design of a robust controller. We resolve these problems by a) performing visual + inertial relative state estimation and b) using a robust line tracker and a nested controller design. Our state estimation exploits high-speed camera images (100Hz) and 70Hz IMU data fused in an Extended Kalman Filter (EKF). We demonstrate results from outdoor experiments for pole-relative hovering, and pole circumnavigation where the operator provides only yaw commands. Lastly, we show results for image-based 3D reconstruction and texture mapping of a pole to demonstrate the usefulness for inspection tasks.

Experiential role of artefacts in cooperative design

The role of material artefacts in supporting distributed and co-located work practices has been well acknowledged within HCI and CSCW research. In this paper, we show that in addition to their ecological, coordinative and organizational support, artefacts also play an 'experiential' role. In this case, artefacts not only improve efficiency or have a purely functional role (e.g. allowing people to complete tasks quickly), but the materiality, use and manifestations of these artefacts bring quality and richness to people's performance and help them make better sense of their everyday lives. In a domain such as industrial design, such artefacts play an important role for supporting creativity and innovation. Based on our ethnographic fieldwork on understanding cooperative design practices of industrial design students and researchers, we describe several experiential practices that are supported by design-related artefacts such as sketches, drawings, physical models and explorative prototypes -- used and developed in designers' everyday work. Our main intention in carrying out this kind of research is to develop technologies to support designers' everyday practices. We believe that with the emergence of ubiquitous computing, there is a growing need to focus on the personal, social and creative side of people's everyday experiences. By focusing on the experiential practices of designers, we can provide a much broader view in the design of new interactive technologies.

Academics in the policy process : engagement with Australian media policy inquiries 2011-2013

This paper critically evaluates the series of inquires that the Australian Labor government undertook during 2011-2013 into reform of Australian media, communications and copyright laws. One important driver of policy reform was the government’s commitment to building a National Broadband Network (NBN), and the implications this had for existing broadcasting and telecommunications policy, as it would constitute a major driver of convergence of media and communications access devices and content platforms. These inquiries included: the Convergence Review of media and communications legislation; the Australian Law Reform Commission (ALRC) review of the National Classification Scheme; and the Independent Media Inquiry (Finkelstein Review) into Media and Media Regulation. One unusual feature of this review process was the degree to which academics were involved in the process, not simply as providers of expert opinion, but as review chairs seconded from their universities. This paper considers the role played by activist groups in all of these inquiries and their relationship to the various participants in the inquiries, as well as the implications of academics being engaged in such inquiries, not simply as activist-scholars, but as those primarily responsible for delivering policy review outcomes. The paper draws upon the concept of "policy windows" in order to better understand the context in which the inquiries took place, and their relative lack of legislative impact.

Fragmentation pathways of 2,3-dimethyl-2,3-dinitrobutane cations in the gas phase

2,3-Dimethyl-2,3-dinitrobutane (DMNB) is an explosive taggant added to plastic explosives during manufacture making them more susceptible to vapour-phase detection systems. In this study, the formation and detection of gas-phase \[M+H](+), \[M+Li](+), \[M+NH(4)](+) and \[M+Na](+) adducts of DMNB was achieved using electrospray ionisation on a triple quadrupole mass spectrometer. The \[M+H](+) ion abundance was found to have a strong dependence on ion source temperature, decreasing markedly at source temperatures above 50 degrees C. In contrast, the \[M+Na](+) ion demonstrated increasing ion abundance at source temperatures up to 105 degrees C. The relative susceptibility of DMNB adduct ions toward dissociation was investigated by collision-induced dissociation. Probable structures of product ions and mechanisms for unimolecular dissociation have been inferred based on fragmentation patterns from tandem mass (MS/MS) spectra of source-formed ions of normal and isotopically labelled DMNB, and quantum chemical calculations. Both thermal and collisional activation studies suggest that the \[M+Na](+) adduct ions are significantly more stable toward dissociation than their protonated analogues and, as a consequence, the former provide attractive targets for detection by contemporary rapid screening methods such as desorption electrospray ionisation mass spectrometry. Copyright (C) 2009 Commonwealth of Australia. Published by John Wiley & Sons, Ltd.

Generation and characterization of ionic and neutral dihydroxy boron B(OH)(2)(+/0) in the gas phase

The dicoordinated borinium ion, dihydroxyborinium, B(OH)(2)(+) is generated from methyl boronic acid CH3B(OH)(2) by dissociative electron ionization and its connectivity confirmed by collisional activation. Neutralization-reionization (NR) experiments on this ion indicate that the neutral B(OH)(2) radical is a viable species in the gas phase. Both vertical neutralization of B(OH)(2)(+) and reionization of B(OH)(2) in the NR experiment are, however, associated with particularly unfavorable Franck-Condon factors. The differences in adiabatic and vertical electron transfer behavior can be traced back to a particular pi stabilization of the cationic species compared to the sp(2)-type neutral radical. Thermochemical data on several neutral and cationic boron compounds are presented based on calculations performed at the G2 level of theory.

A soluble activin Type IIA receptor induces bone formation and improves skeletal integrity

Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-� signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility.

Author in waiting : self-portrait of Peter Goldsworthy as a boy

Review of His Stupid Boyhood by Peter Goldsworthy (Hamish Hamilton, 2013).

Physical activity correlates in adolescent girls who differ by weight status

Objective This study compared correlates of physical activity (PA) among African-American and white girls of different weight groups to guide future interventions. Research Methods and Procedures Participants were 1015 girls (mean age, 14.6 years; 45% African-American) from 12 high schools in South Carolina who served as control subjects for a school-based intervention. Post-intervention measures obtained at the end of ninth grade were used. PA was measured using the Three-Day PA Recall, and a questionnaire measured social-cognitive and environmental variables thought to mediate PA. Height and weight were measured, and BMI was calculated. Girls were stratified by race and categorized into three groups, based on BMI percentiles for girls from CDC growth charts: normal (BMI < 85th percentile), at risk (BMI, 85th to 94th percentile), and overweight (BMI ≥ 95th percentile). Girls were further divided into active and low-active groups, based on a vigorous PA standard (average of one or more 30-minute blocks per day per 3-day period). Mixed-model ANOVA was used to compare factors among groups, treating school as a random effect Results None of the social-cognitive or environmental variables differed by weight status for African-American or white girls. Perceived behavioral control and sports team participation were significantly higher in girls who were more active, regardless of weight or race group. In general, social-cognitive variables seem to be more related to activity in white girls, whereas environmental factors seem more related to activity in African-American girls. Discussion PA interventions should be tailored to the unique needs of girls based on PA levels and race, rather than on weight status alone.

The analysis of large scale data taken from the world groundnut (Arachis hypogaea L.) germplasm collection. II. Two-way data with mixed data types

As a sequel to a paper that dealt with the analysis of two-way quantitative data in large germplasm collections, this paper presents analytical methods appropriate for two-way data matrices consisting of mixed data types, namely, ordered multicategory and quantitative data types. While various pattern analysis techniques have been identified as suitable for analysis of the mixed data types which occur in germplasm collections, the clustering and ordination methods used often can not deal explicitly with the computational consequences of large data sets (i.e. greater than 5000 accessions) with incomplete information. However, it is shown that the ordination technique of principal component analysis and the mixture maximum likelihood method of clustering can be employed to achieve such analyses. Germplasm evaluation data for 11436 accessions of groundnut (Arachis hypogaea L.) from the International Research Institute of the Semi-Arid Tropics, Andhra Pradesh, India were examined. Data for nine quantitative descriptors measured in the post-rainy season and five ordered multicategory descriptors were used. Pattern analysis results generally indicated that the accessions could be distinguished into four regions along the continuum of growth habit (or plant erectness). Interpretation of accession membership in these regions was found to be consistent with taxonomic information, such as subspecies. Each growth habit region contained accessions from three of the most common groundnut botanical varieties. This implies that within each of the habit types there is the full range of expression for the other descriptors used in the analysis. Using these types of insights, the patterns of variability in germplasm collections can provide scientists with valuable information for their plant improvement programs.

Interaction between Arabidopsis Brca2 and its partners Rad51, Dmc1, and Dss1

The Arabidopsis (Arabidopsis thaliana) orthologs of Brca2, a protein whose mutations are involved in breast cancer in humans, were previously shown to be essential at meiosis. In an attempt to better understand the Brca2-interacting properties, we examined four partners of the two isoforms of Brca2 identified in Arabidopsis (AtRad51, AtDmc1, and two AtDss1 isoforms). The two Brca2 and the two Dss1 isoforms are named AtBrca2(IV), AtBrca2(V), AtDss1(I), and AtDss1(V) after their chromosomal localization. We first show that both AtBrca2 proteins can interact with either AtRad51 or AtDmc1 in vitro, and that the N-terminal region of AtBrca2 is responsible for these interactions. More specifically, the BRC motifs (so called because iterated in the Brca2 protein) in Brca2 are involved in these interactions: BRC motif number 2 (BRC2) alone can interact with AtDmc1, whereas BRC motif number 4 (BRC4) recognizes AtRad51. The human Rad51 and Dmc1 proteins themselves can interact with either the complete (HsRad51) or a shorter version of AtBrca2 (HsRad51 or HsDmc1) that comprises all four BRC motifs. We also identified two Arabidopsis isoforms of Dss1, another known partner of Brca2 in other organisms. Although all four Brca2 and Dss1 proteins are much conserved, AtBrca2(IV) interacts with only one of these AtDss1 proteins, whereas AtBrca2(V) interacts with both of them. Finally, we show for the first time that an AtBrca2 protein could bind two different partners at the same time: AtRad51 and AtDss1(I), or AtDmc1 and AtDss1(I).

Examples illustrating the use of renormalization techniques for singularly perturbed differential equations

With nine examples, we seek to illustrate the utility of the Renormalization Group approach as a unification of other asymptotic and perturbation methods.