Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. © 2005 Wiley-Liss, Inc.

A comprehensive neuropsychiatric study of elderly twins: The Older Australian Twins Study

The Older Australian Twins Study (OATS) was recently initiated to investigate genetic and environmental factors and their associations and interactions in healthy brain ageing and ageing-related neurocognitive disorders. The study extends the classic MZ-DZ design to include one or two equivalently aged siblings for each twin pair and utilizes the rich resources of the Australian Twin Registry. The study has a number of distinguishing features including comprehensive psychiatric, neuropsychological, cardiovascular, metabolic, and neuroimaging assessments, a longitudinal design and links with a brain donor program. The study measures many behavioral and environmental factors, but in particular lifetime physical and mental activity, physical and psychological trauma, loss of parent early in life, later losses and life events, early-life socioeconomic environment, alcohol and drug use, occupational exposure, and nutrition. It also includes comprehensive cardiovascular assessment, blood biochemistry, genetics and proteomics. The socio-demographic and health data on the first 172 pairs of twins participating in this study are presented. Prevalence of mild cognitive impairment is 12.8% and of dementia 1.5% in the sample. The target sample size is 1000, with at least 400 pairs of twins aged 65-90 years. The cohort will be assessed every two years, with in-depth assessments being repeated. OATS offers an excellent opportunity for collaboration with other similar studies as well as researchers who share the same interests.

‘True Blood’ the critical care story: An audit of blood sampling practice across three adult, paediatric and neonatal intensive care settings

Background Anaemia is common in critically ill patients, and has a significant negative impact on patients' recovery. Blood conservation strategies have been developed to reduce the incidence of iatrogenic anaemic caused by sampling for diagnostic testing. Objectives Describe practice and local guidelines in adult, paediatric and neonatal Australian intensive care units (ICUs) regarding blood sampling and conservation strategies. Methods Cross-sectional descriptive study, conducted July 2013 over one week in single adult, paediatric and neonatal ICUs in Brisbane. Data were collected on diagnostic blood samples obtained during the study period, including demographic and acuity data of patients. Institutional blood conservation practice and guidelines were compared against seven evidence-based recommendations. Results A total of 940 blood sampling episodes from 96 patients were examined across three sites. Arterial blood gas was the predominant reason for blood sampling in each unit, accounting for 82% of adult, 80% of paediatric and 47% of neonatal samples taken (p <. 0.001). Adult patients had significantly more median [IQR] samples per day in comparison to paediatrics and neonates (adults 5.0 [2.4]; paediatrics 2.3 [2.9]; neonatal 0.7 [2.7]), which significantly increased median [IQR] blood sampling costs per day (adults AUD$101.11 [54.71]; paediatrics AUD$41.55 [56.74]; neonatal AUD$8.13 [14.95]; p <. 0.001). The total volume of samples per day (median [IQR]) was also highest in adults (adults 22.3. mL [16.8]; paediatrics 5.0. mL [1.0]; neonates 0.16. mL [0.4]). There was little information about blood conservation strategies in the local clinical practice guidelines, with the adult and neonatal sites including none of the seven recommendations. Conclusions There was significant variation in blood sampling practice and conservation strategies between critical care settings. This has implications not only for anaemia but also infection control and healthcare costs.

Web crippling tests of rivet fastened rectangular hollow flange channel beams under two flange load cases

Recent research on hollow flange beams has led to the development of an innovative rectangular hollow flange channel beam (RHFCB) for use in floor systems. The new RHFCB is a mono-symmetric structural section made by intermittently rivet fastening two torsionally rigid closed rectangular hollow flanges to a web plate element, which allows section optimisation by selecting appropriate combinations of web and flange widths and thicknesses. However, the current design rules for cold-formed steel sections are not directly applicable to rivet fastened RHFCBs. To date, no investigation has been conducted on their web crippling behaviour and strengths. Hence an experimental study was conducted to investigate the web crippling behaviour and capacities of rivet fastened RHFCBs under End Two Flange (ETF) and Interior Two Flange (ITF) load cases. It showed that RHFCBs failed by web crippling, flange crushing and their combinations. Comparison of ultimate web crippling capacities with the predictions from the design equations in AS/NZS 4600 and AISI S100 showed that the current design equations are unconservative for rivet fastened RHFCB sections under ETF and ITF load cases. Hence new equations were proposed to determine the web crippling capacities of rivet fastened RHFCBs. These equations can also be used to predict the capacities of RHFCBs subject to combined web crippling and flange crushing conservatively. However, new capacity equations were proposed in the case of flange crushing failures that occurred in thinner flanges with smaller bearing lengths. This paper presents the details of this web crippling experimental study of RHFCB sections and the results.

Shear tests of hollow flange channel beams with real support conditions

This paper presents the details of experimental studies on the effect of real support conditions on the shear strength of hollow flange channel beams, known as LiteSteel beams (LSB). The LSB has a unique shape of a channel beam with two rectangular hollow flanges, made using a unique manufacturing process. In many applications in the building industry LSBs are used with only one web side plate (WSP) at their supports. The WSPs are also often not full height plates. Past research studies showed that these real support connections did not provide the required simply supported conditions. Many studies have been carried out to evaluate the behaviour and design of LSBs with simply supported conditions subject to pure bending and predominant shear actions. To date, however, no investigation has been conducted into the effect of real support conditions on the shear strength of LSBs. Hence a detailed experimental study based on 25 shear tests was undertaken to investigate the shear behaviour and strength of LSBs with real support conditions. Simply supported test specimens of LSBs with aspect ratios of 1.0 and 1.5 were loaded at mid-span until failure. It was found that the effect of using one WSP on the shear behaviour of LSB is significant and there is about 25% shear capacity reduction due to the lateral movement of the bottom flange at the supports. Shear capacity of LSB was also found to decrease when full height WSPs were not used. Suitably improved support connections were developed to improve the shear capacity of LSBs based on test results. Details of the recommended support connections and shear capacity results are given in this paper.

Assessing acculturation over time: A four-year prospective study of Asian American young adults

Acculturation is commonly defined as a dynamic and multidimensional process in which individuals and groups change over time when coming into contact with another culture. Despite the emphasis on acculturation as a process of change over time, few researchers have directly assessed this hypothesis. The current study first identifies and then examines "stable" and "dynamic" dimensions of acculturation within a 4-year prospective study of 433 first- and second-generation Chinese- and Korean-American college students. Separate growth model analyses revealed significant linear change for first-generation students toward greater U.S. acculturation. In comparison, tests of linear and quadratic change for second-generation students were not significant. When stratifying by gender, acculturation increased for women but there was no significant change in acculturation for men. While all students reported increases in alcohol consumption over the study period, changes in acculturation predicted changes in alcohol consumption only for women. Chinese men showed greater increases in alcohol consumption than Korean men but there was no effect for ethnicity among women. There was significant individual variability in the models, which underscores the importance of examining change prospectively through within and between person analyses. The findings highlight the importance of examining acculturation changes over time for different migrant groups with implications for further development of acculturation measures, research methodologies, and health interventions. More prospective research designs of acculturation are needed to examine changes in health behavior and overall adaptation across migrant groups at varying stages of development.

‘Just choose the easy option’: Students talk about alcohol use and social influence

Previous research into young people’s drinking behaviour has studied how social practices influence their actions and how they negotiate drinking-related identities. Here, adopting the perspective of discursive psychology we examine how, for young people, social influences are bound up with issues of drinking and of identity. We conducted 19 focus groups with undergraduate students in Australia aged between 18 and 24 years. Thematic analysis of participants’ accounts for why they drink or do not drink was used to identify passages of talk that referred to social influence, paying particular attention to terms such as ‘pressure’ and ‘choice’. These passages were then analysed in fine-grained detail, using discourse analysis, to study how participants accounted for social influence. Participants treated their behaviour as accountable and produced three forms of account that: (1) minimised the choice available to them, (2) explained drinking as culture and (3) described resisting peer pressure. They also negotiated gendered social dynamics related to drinking. These forms of account allowed the participants to avoid individual responsibility for drinking or not drinking. These findings demonstrate that the effects of social influence on young people’s drinking behaviour cannot be assumed, as social influence itself becomes negotiable within local contexts of talk about drinking.

Access to essential medicines: Public health and international law

Historically, there have been intense conflicts over the ownership and exploitation of pharmaceutical drugs and diagnostic tests dealing with infectious diseases. Throughout the 1980’s, there was much scientific, legal, and ethical debate about which scientific group should be credited with the discovery of the human immunodeficiency virus, and the invention of the blood test devised to detect antibodies to the virus. In May 1983, Luc Montagnier, Françoise Barré-Sinoussi, and other French scientists from the Pasteur Institute in Paris, published a paper in Science, detailing the discovery of a virus called lymphadenopathy (LAV). A scientific rival, Robert Gallo of the National Cancer Institute, identified the AIDS virus and published his findings in the May 1984 issue of Science. In May 1985, the United States Patent and Trademark Office awarded the American patent for the AIDS blood test to Gallo and the Department of Health and Human Services. In December 1985, the Institut Pasteur sued the Department of Health and Human Services, contending that the French were the first to identify the AIDS virus and to invent the antibody test, and that the American test was dependent upon the French research. In March 1987, an agreement was brokered by President Ronald Reagan and French Prime Minister Jacques Chirac, which resulted in the Department of Health and Human Services and the Institut Pasteur sharing the patent rights to the blood test for AIDS. In 1992, the Federal Office of Research Integrity found that Gallo had committed scientific misconduct, by falsely reporting facts in his 1984 scientific paper. A subsequent investigation by the National Institutes of Health, the United States Congress, and the US attorney-general cleared Gallo of any wrongdoing. In 1994, the United States government and French government renegotiated their agreement regarding the AIDS blood test patent, in order to make the distribution of royalties more equitable... The dispute between Luc Montagnier and Robert Gallo was not an isolated case of scientific rivalry and patent races. It foreshadowed further patent conflicts over research in respect of HIV/AIDS. Michael Kirby, former Justice of the High Court of Australia diagnosed a clash between two distinct schools of philosophy - ‘scientists of the old school... working by serendipity with free sharing of knowledge and research’, and ‘those of the new school who saw the hope of progress as lying in huge investments in scientific experimentation.’ Indeed, the patent race between Robert Gallo and Luc Montagnier has been a precursor to broader trade disputes over access to essential medicines in the 1990s and 2000s. The dispute between Robert Gallo and Luc Montagnier captures in microcosm a number of themes of this book: the fierce competition for intellectual property rights; the clash between sovereign states over access to medicines; the pressing need to defend human rights, particularly the right to health; and the need for new incentives for research and development to combat infectious diseases as both an international and domestic issue.

General motor vehicle drivers' knowledge and practices regarding drink driving in Yinchuan and Guangzhou, China

Objective: Drink driving contributes to significant levels of injury and economic loss in China but is not well researched. This study examined knowledge, drink-driving practices, and alcohol misuse problems among general drivers in Yinchuan. The objectives were to gain a better understanding of drink driving in Yinchuan, identify areas that need to be addressed, and compare the results with a similar study in Guangzhou. Methods: This was a cross-sectional study with a survey designed to collect information on participants’ demographic characteristics and their knowledge and practices in relation to drinking and driving. The survey was composed of questions on knowledge and practices in relation to drink driving and was administered to a convenience sample of 406 drivers. Alcohol misuse problems were assessed by using the Alcohol Use Disorders Identification Test (AUDIT). Results: Males accounted for the main proportion of drivers sampled from the general population (“general drivers”). A majority of general drivers in both cities knew that drunk driving had become a criminal offense in 2011; however, knowledge of 2 legal blood alcohol concentration (BAC) limits was quite low. Fewer drivers in Yinchuan (22.6%) than in Guangzhou (27.9) reported having been stopped by police conducting breath alcohol testing at least once in the last 12 months. The mean AUDIT score in Yinchuan (M = 8.2) was higher than that in Guangzhou (M = 7.4), and the proportion of Yinchuan drivers with medium or higher alcohol misuse problems (31.2%) was correspondingly higher than in Guangzhou (23.1%). In Yinchuan, males had a significantly higher AUDIT score than females (t = 3.454, P < .001), similar to Guangzhou. Multiple regression analyses were conducted on potential predictors of the AUDIT score (age, gender, monthly income, education level, years licensed, and age started drinking). There were significant individual contributions of gender (beta = 0.173, P = .09) and age at which drinking started (beta = 0.141, P = .033), but the overall model for Yinchuan was not significant, unlike Guangzhou. Conclusions: The results show that there are shortfalls in knowledge of the legislation and how to comply with it and deficiencies in police enforcement. In addition, there was evidence of drink driving and drink riding at high levels in both cities. Recommendations are made to address these issues.

Health and guardianship law: Children, consent and the refusal of blood products: A recent Queensland case

This column provides a summary of the recent decision of The Hospital v T [2015] QSC 185

Exploring the influences of country-level factors on mature-aged women’s drink driving attitudes

The current study examined drink driving attitudes among mature-aged women in Sweden and Australia, two countries with a Blood Alcohol Concentration (BAC) limit of 0.02% and 0.05%, respectively. The study aimed to identify attitudes that might influence drink driving tendency among this group of women and further show how these attitudes vary across countries. Using an ethnographic approach, 15 mature-aged women (Sweden: mean age = 52.5years, SD = 4.8; Australia: mean age 52.2 years, SD = 3.4) were interviewed in each country. General patterns and themes from the data were developed using thematic analysis methods. The findings indicate that while women in both countries viewed drink driving negatively, the understanding of what the concept entailed differed between the two samples. The Swedish women appeared to cognitively separate alcohol consumption and driving, and consequently, drink driving was often spoken of as driving after any alcohol consumption. The Australian women’s understanding of drink driving was more closely related to the legal BAC limit. However, for some Australian women, a “Grey Zone” existed, which denoted driving with a BAC of just above the enforceable limit. While illegal, these instances were subjectively seen as similar to driving with a BAC of just under the legal limit and therefore not morally reprehensible. The practice of cognitively separating drinking from driving appeared to have implications for the tendency to drink and drive among the interviewed women. These findings are discussed in relation to current policy and legislation in Australia and the need for further research into mature-aged women’s drink driving is outlined.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Background: Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.Methods: The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with 'biopsy-confirmed' CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.Results: Only five 'biopsy-confirmed' patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.Conclusions: Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies. © 2013 Anderson et al.; licensee BioMed Central Ltd.

Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects

Introduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort. Methods: A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs). Results: A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism. Conclusions: We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.

Total transcriptome, proteome, and allergome of Johnson grass pollen, which is important for allergic rhinitis in subtropical regions

Background Genomic data are lacking for many allergen sources. To circumvent this limitation, we implemented a strategy to reveal the repertoire of pollen allergens of a grass with clinical importance in subtropical regions, where an increasing proportion of the world's population resides. Objective We sought to identify and immunologically characterize the allergenic components of the Panicoideae Johnson grass pollen (JGP; Sorghum halepense). Methods The total pollen transcriptome, proteome, and allergome of JGP were documented. Serum IgE reactivities with pollen and purified allergens were assessed in 64 patients with grass pollen allergy from a subtropical region. Results Purified Sor h 1 and Sor h 13 were identified as clinically important allergen components of JGP with serum IgE reactivity in 49 (76%) and 28 (43.8%), respectively, of patients with grass pollen allergy. Within whole JGP, multiple cDNA transcripts and peptide spectra belonging to grass pollen allergen families 1, 2, 4, 7, 11, 12, 13, and 25 were identified. Pollen allergens restricted to subtropical grasses (groups 22-24) were also present within the JGP transcriptome and proteome. Mass spectrometry confirmed the IgE-reactive components of JGP included isoforms of Sor h 1, Sor h 2, Sor h 13, and Sor h 23. Conclusion Our integrated molecular approach revealed qualitative differences between the allergenic components of JGP and temperate grass pollens. Knowledge of these newly identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with grass pollen allergy in subtropical regions and reduce the burden of allergic respiratory disease globally.

Molecular cloning, expression and immunological characterisation of Pas n 1, the major allergen of Bahia grass Paspalum notatum pollen

Bahia grass, Paspalum notatum, is a clinically important subtropical grass with a prolonged pollination season from spring to autumn. We aimed to clone and characterise the major Bahia grass pollen allergen, Pas n 1. Grass pollen-allergic patients presenting to a tertiary hospital allergy clinic were tested for IgE reactivity with Bahia grass pollen extract by skin prick testing, ImmunoCAP, ELISA and immunoblotting. Using primers deduced from the N-terminal peptide sequence of a group 1 allergen of Bahia grass pollen extract separated by two-dimensional gel electrophoresis, the complete Pas n 1 cDNA was obtained by rapid amplification of cDNA ends and cloned. Biological relevance of recombinant Pas n 1 expressed in Escherichia coli was assessed by serum IgE reactivity and basophil activation. Twenty-nine of 34 (85%) consecutive patients presenting with grass pollen allergy were skin prick test positive to Bahia grass pollen. The Pas n 1 cDNA has sequence homology with the β-expansin 1 glycoprotein family and is more closely related to the maize pollen group 1 allergen (85% identity) than to ryegrass Lol p 1 or Timothy grass Phl p 1 (64 and 66% identity, respectively). rPas n 1 reacted with serum IgE in 47 of 55 (85%) Bahia grass pollen-allergic patients, activated basophils and inhibited serum IgE reactivity with the 29 kDa band of Bahia grass pollen extract. In conclusion the cDNA for the major group 1 allergen of the subtropical Bahia grass pollen, Pas n 1, was identified and cloned. rPas n 1 is immunologically active and is a valuable reagent for diagnosis and specific immunotherapy of grass pollen allergy.