Low birth weight in MZ twins discordant for birth weight is associated with shorter telomere length and lower IQ, but not anxiety/depression in later life

Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.

Loci affecting gamma-glutamyl transferase in adults and adolescents show age x SNP interaction and cardiometabolic disease associations

Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in an intergenic region of chromosome 1, P = 3.9 x 10(-8); rs944002 in C14orf73 on chromosome 14, P = 4.7 x 10(-13); rs340005 in RORA on chromosome 15, P = 2.4 x 10(-8)), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P(HET) = 5.6 x 10(-12) at rs6519520). Pathway analysis of significant and suggestive single-nucleotide polymorphism associations showed significant overlap between genes affecting GGT and those affecting common metabolic and inflammatory diseases, and identified the hepatic nuclear factor (HNF) family as controllers of a network of genes affecting GGT. Our results reinforce the disease associations of GGT and demonstrate that control by the GGT1 locus varies with age.

Educational attainment: A genome wide association study in 9538 Australians

BACKGROUND Correlations between Educational Attainment (EA) and measures of cognitive performance are as high as 0.8. This makes EA an attractive alternative phenotype for studies wishing to map genes affecting cognition due to the ease of collecting EA data compared to other cognitive phenotypes such as IQ. METHODOLOGY In an Australian family sample of 9538 individuals we performed a genome-wide association scan (GWAS) using the imputed genotypes of approximately 2.4 million single nucleotide polymorphisms (SNP) for a 6-point scale measure of EA. Top hits were checked for replication in an independent sample of 968 individuals. A gene-based test of association was then applied to the GWAS results. Additionally we performed prediction analyses using the GWAS results from our discovery sample to assess the percentage of EA and full scale IQ variance explained by the predicted scores. RESULTS The best SNP fell short of having a genome-wide significant p-value (p = 9.77x10(-7)). In our independent replication sample six SNPs among the top 50 hits pruned for linkage disequilibrium (r(2)<0.8) had a p-value<0.05 but only one of these SNPs survived correction for multiple testing--rs7106258 (p = 9.7*10(-4)) located in an intergenic region of chromosome 11q14.1. The gene based test results were non-significant and our prediction analyses show that the predicted scores explained little variance in EA in our replication sample. CONCLUSION While we have identified a polymorphism chromosome 11q14.1 associated with EA, further replication is warranted. Overall, the absence of genome-wide significant p-values in our large discovery sample confirmed the high polygenic architecture of EA. Only the assembly of large samples or meta-analytic efforts will be able to assess the implication of common DNA polymorphisms in the etiology of EA.

Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia

Genome-wide association studies followed by replication provide a powerful approach to map genetic risk factors for asthma. We sought to search for new variants associated with asthma and attempt to replicate the association with four loci reported previously (ORMDL3, PDE4D, DENND1B and IL1RL1). Genome-wide association analyses of individual single nucleotide polymorphisms (SNPs), rare copy number variants (CNVs) and overall CNV burden were carried out in 986 asthma cases and 1846 asthma-free controls from Australia. The most-associated locus in the SNP analysis was ORMDL3 (rs6503525, P = 4.8 x 10(-)(7)). Five other loci were associated with P < 10(-)(5), most notably the chemokine CXC motif ligand 14 (CXCL14) gene (rs31263, P = 7.8 x 10(-)(6)). We found no evidence for association with the specific risk variants reported recently for PDE4D, DENND1B and ILR1L1. However, a variant in IL1RL1 that is in low linkage disequilibrium with that reported previously was associated with asthma risk after accounting for all variants tested (rs10197862, gene wide P = 0.01). This association replicated convincingly in an independent cohort (P = 2.4 x 10(-)(4)). A 300-kb deletion on chromosome 17q21 was associated with asthma risk, but this did not reach experiment-wide significance. Asthma cases and controls had comparable CNV rates, length and number of genes affected by deletions or duplications. In conclusion, we confirm the association between asthma risk and variants in ORMDL3 and identify a novel risk variant in IL1RL1. Follow-up of the 17q21 deletion in larger cohorts is warranted.

Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune Control

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10−28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10−14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10−9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

Corporate Social Responsibility (CSR) in junior and mid-tier Australian resources companies operating in developing nations - beyond the public relations offensive

NIt is now widely accepted that corporations have a responsibility to benefit society, as well as generate profit. This study used institutional theory to explore how the complex and contested notion of corporate social responsibility is understood and practiced by junior and mid-tier Australian resources companies operating in the world's most impoverished countries. The study found that CSR meaning and practice in this large but little researched group of companies was shaped by complex pressures at the global, industry, organisational and individual levels. Importantly, the study also revealed striking contradictions and ambiguities between participants' CSR aspirations and their actions and accountability.

Threats and Promises: The Promotion of Artificial Lighting to Women Consumers in the United States, 1880s – 1960s

This article examines the development of a specific gendered discourse in the United States in the first half of the twentieth century that united key beliefs about feminine beauty, identity, and the domestic interior with particular electric lighting technologies and effects. Largely driven by the electrical industry’s marketing rhetoric, American women were encouraged to adopt electric lighting as a beauty aid and ally in a host of domestic tasks. Drawing evidence from a number of primary texts, including women’s magazines, lighting and electrical industry trade journals, manufacturer-generated marketing materials, and popular home decoration and beauty advice literature, this study shifts the focus away from lighting as a basic utility, demonstrating the ways in which modern electric illumination was culturally constructed as a desirable personal and environmental beautifier as well as a means of harmonizing the domestic interior.

Decision trees for detection of activity intensity in youth with cerebral palsy

PURPOSE To develop and test decision tree (DT) models to classify physical activity (PA) intensity from accelerometer output and Gross Motor Function Classification System (GMFCS) classification level in ambulatory youth with cerebral palsy (CP); and 2) compare the classification accuracy of the new DT models to that achieved by previously published cut-points for youth with CP. METHODS Youth with CP (GMFCS Levels I - III) (N=51) completed seven activity trials with increasing PA intensity while wearing a portable metabolic system and ActiGraph GT3X accelerometers. DT models were used to identify vertical axis (VA) and vector magnitude (VM) count thresholds corresponding to sedentary (SED) (<1.5 METs), light PA (LPA) (>/=1.5 and <3 METs) and moderate-to-vigorous PA (MVPA) (>/=3 METs). Models were trained and cross-validated using the 'rpart' and 'caret' packages within R. RESULTS For the VA (VA_DT) and VM decision trees (VM_DT), a single threshold differentiated LPA from SED, while the threshold for differentiating MVPA from LPA decreased as the level of impairment increased. The average cross-validation accuracy for the VC_DT was 81.1%, 76.7%, and 82.9% for GMFCS levels I, II, and III, respectively. The corresponding cross-validation accuracy for the VM_DT was 80.5%, 75.6%, and 84.2%, respectively. Within each GMFCS level, the decision tree models achieved better PA intensity recognition than previously published cut-points. The accuracy differential was greatest among GMFCS level III participants, in whom the previously published cut-points misclassified 40% of the MVPA activity trials. CONCLUSION GMFCS-specific cut-points provide more accurate assessments of MVPA levels in youth with CP across the full spectrum of ambulatory ability.

Reliability and validity of objective measures of physical activity in youth with cerebral palsy who are ambulatory

BACKGROUND Physical therapy for youth with cerebral palsy (CP) who are ambulatory includes interventions to increase functional mobility and participation in physical activity (PA). Thus, reliable and valid measures are needed to document PA in youth with CP. OBJECTIVE The purpose of this study was to evaluate the inter-instrument reliability and concurrent validity of 3 accelerometer-based motion sensors with indirect calorimetry as the criterion for measuring PA intensity in youth with CP. METHODS Fifty-seven youth with CP (mean age=12.5 years, SD=3.3; 51% female; 49.1% with spastic hemiplegia) participated. Inclusion criteria were: aged 6 to 20 years, ambulatory, Gross Motor Function Classification System (GMFCS) levels I through III, able to follow directions, and able to complete the full PA protocol. Protocol activities included standardized activity trials with increasing PA intensity (resting, writing, household chores, active video games, and walking at 3 self-selected speeds), as measured by weight-relative oxygen uptake (in mL/kg/min). During each trial, participants wore bilateral accelerometers on the upper arms, waist/hip, and ankle and a portable indirect calorimeter. Intraclass coefficient correlations (ICCs) were calculated to evaluate inter-instrument reliability (left-to-right accelerometer placement). Spearman correlations were used to examine concurrent validity between accelerometer output (activity and step counts) and indirect calorimetry. Friedman analyses of variance with post hoc pair-wise analyses were conducted to examine the validity of accelerometers to discriminate PA intensity across activity trials. RESULTS All accelerometers exhibited excellent inter-instrument reliability (ICC=.94-.99) and good concurrent validity (rho=.70-.85). All accelerometers discriminated PA intensity across most activity trials. LIMITATIONS This PA protocol consisted of controlled activity trials. CONCLUSIONS Accelerometers provide valid and reliable measures of PA intensity among youth with CP.

Validity of the OMNI rating of perceived exertion scale for children and adolescents with cerebral palsy

Aim This study evaluated the validity of the OMNI Walk/Run Rating of Perceived Exertion (OMNI-RPE) scores with heart rate and oxygen consumption (VO2) for children and adolescents with cerebral palsy (CP). Method Children and adolescents with CP, aged 6 to 18 years and Gross Motor Function Classification System (GMFCS) levels I to III completed a physical activity protocol with seven trials ranging in intensity from sedentary to moderate-to-vigorous. VO2 and heart rate were recorded during the physical activity trials using a portable indirect calorimeter and heart rate monitor. Participants reported OMNI-RPE scores for each trial. Concurrent validity was assessed by calculating the average within-subject correlation between OMNI-RPE ratings and the two physiological indices. Results For the correlational analyses, 48 participants (22 males, 26 females; age 12y 6mo, SD 3y 4mo) had valid bivariate data for VO2 and OMNI-RPE, while 40 participants (21 males, 19 females; age 12y 5mo, SD 2y 9mo) had valid bivariate data for heart rate and OMNI-RPE. VO2 (r=0.80; 95% CI 0.66–0.88) and heart rate (r=0.83; 95% CI 0.70–0.91) were moderately to highly correlated to OMNI-RPE scores. No difference was found for the correlation of physiological data and OMNI-RPE scores across the three GMFCS levels. The OMNI-RPE scores increased significantly in a dose-response manner (F6,258=116.1, p<0.001) as exercise intensity increased from sedentary to moderate-to-vigorous. Interpretation OMNI-RPE is a clinically feasible option to monitor exercise intensity in ambulatory children and adolescents with CP.

Elevated levels of PFOS and PFHxS in firefighters exposed to aqueous film forming foam (AFFF)

Exposure to aqueous film forming foam (AFFF) was evaluated in 149 firefighters working at AFFF training facilities in Australia by analysis of PFOS and related compounds in serum. A questionnaire was designed to capture information about basic demographic factors, lifestyle factors and potential occupational exposure (such as work history and self-reported skin contact with foam). The results showed that a number of factors were associated with PFAA serum concentrations. Blood donation was found to be linked to low PFAA levels, and the concentrations of PFOS and PFHxS were found to be positively associated with years of jobs with AFFF contact. The highest levels of PFOS and PFHxS were one order of magnitude higher compared to the general population in Australia and Canada. Study participants who had worked ten years or less had levels of PFOS that were similar to or only slightly above those of the general population. This coincides with the phase out of 3M AFFF from all training facilities in 2003, and suggests that the exposures to PFOS and PFHxS in AFFF have declined in recent years. Self-reporting of skin contact and frequency of contact were used as an index of exposure. Using this index, there was no relationship between PFOS levels and skin exposure. This index of exposure is limited as it relies on self-report and it only considers skin exposure to AFFF, and does not capture other routes of potential exposure. Possible associations between serum PFAA concentrations and five biochemical outcomes were assessed. The outcomes were serum cholesterol, triglycerides, high-density lipoproteins, low density lipoproteins, and uric acid. No statistical associations between any of these endpoints and serum PFAA concentrations were observed.

Novel fluorinated surfactants tentatively identified in firefighters using liquid chromatography quadrupole time-of flight tandem mass spectrometry and a case-control approach

Fluorinated surfactant-based aqueous film-forming foams (AFFFs) are made up of per- and polyfluorinated alkyl substances (PFAS) and are used to extinguish fires involving highly flammable liquids. The use of perfluorooctanesulfonic acid (PFOS) and other perfluoroalkyl acids (PFAAs) in some AFFF formulations has been linked to substantial environmental contamination. Recent studies have identified a large number of novel and infrequently reported fluorinated surfactants in different AFFF formulations. In this study, a strategy based on a case-control approach using quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) and advanced statistical methods has been used to extract and identify known and unknown PFAS in human serum associated with AFFF-exposed firefighters. Two target sulfonic acids [PFOS and perfluorohexanesulfonic acid (PFHxS)], three non-target acids [perfluoropentanesulfonic acid (PFPeS), perfluoroheptanesulfonic acid (PFHpS), and perfluorononanesulfonic acid (PFNS)], and four unknown sulfonic acids (Cl-PFOS, ketone-PFOS, ether-PFHxS, and Cl-PFHxS) were exclusively or significantly more frequently detected at higher levels in firefighters compared to controls. The application of this strategy has allowed for identification of previously unreported fluorinated chemicals in a timely and cost-efficient way.

Case study 1: Nursing informatics and eHealth in Australia

There are currently many changes happening in nursing and healthcare in Australia. Healthcare reform has been high on the national government agenda and has created many changes in healthcare including eHealth. Healthcare information technologies and informatics are providing many challenges and excitement for the future of healthcare in Australia. The challenge for professional nursing organisations and nursing leaders of Australia is to be proactive in developments and initiatives for nursing to remain visible and viable in health care systems to safeguard the profession for the future as health care reform is implemented.

Identifying advanced practice: A national survey of a nursing workforce

Background The size and flexibility of the nursing workforce has positioned nursing as central to the goals of health service improvement. Nursing's response to meeting these goals has resulted in proliferation of advanced practice nursing with a confusing array of practice profiles, titles and roles. Whilst numerous models and definitions of advanced practice nursing have been developed there is scant published research of significant scope that supports these models. Consequently there is an ongoing call in the literature for clarity and stability in nomenclature, and confusion in the health industry on how to optimise the utility of advanced practice nursing. Objectives To identify and delineate advanced practice from other levels of nursing practice through examination of a national nursing workforce. Design A cross-sectional electronic survey of nurses using the validated Advanced Practice Role Delineation tool based on the Strong Model of Advanced Practice. Participants Study participants were registered nurses employed in a clinical service environment across all states and territories of Australia. Methods A sample of 5662 registered nurses participated in the study. Domain means for each participant were calculated then means for nursing position titles were calculated. Position titles were grouped by delineation and were compared with one-way analysis of variance on domain means. The alpha for all tests was set at 0.05. Significant effects were examined with Scheffe post hoc comparisons to control for Type 1 error. Results The survey tool was able to identify position titles where nurses were practicing at an advanced level and to delineate this cohort from other levels of nursing practice, including nurse practitioner. The results show that nurses who practice at an advanced level are characterised by high mean scores across all Domains of the Strong Model of Advanced Practice. The mean scores of advanced practice nurses were significantly different from nurse practitioners in the Direct Care Domain and significantly different from other levels of nurse across all domains. Conclusions The study results show that the nurse practitioner, advanced practice nurse and foundation level registered nurse have different patterns of practice and the Advanced Practice Role Delineation tool has the capacity to clearly delineate and define advanced practice nursing. These findings make a significant contribution to the international debate and show that the profession can now identify what is and what is not advanced practice in nursing.