Education for Australia’s information future

Digital disruption and an increasingly networked society drive rapid change in many professions and a corresponding need for change in tertiary education. Across the world, information education has, to date, prepared graduates for employment in discrete professions, such as librarianship, records management, archives, and teacher librarianship. However, contemporary information practices are less defined and are demanding of new professional skill-sets and understandings. This paper reports a study that consulted Australia’s tertiary academics about the current circumstances of information education in the academy and elicited a vision and a concern for future directions in Australian information education.

Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by lung endothelial dysfunction and vascular remodeling. Recently, bone marrow progenitor cells have been localized to PAH lungs, raising the question of their role in disease progression. Independently, serotonin (5-HT) and its receptors have been identified as contributors to the PAH pathogenesis. We hypothesized that 1 of these receptors, 5-HT(2B), is involved in bone marrow stem cell mobilization that participates in the development of PAH and pulmonary vascular remodeling. A first study revealed expression of 5-HT(2B) receptors by circulating c-kit(+) precursor cells, whereas mice lacking 5-HT(2B) receptors showed alterations in platelets and monocyte-macrophage numbers, and in myeloid lineages of bone marrow. Strikingly, mice with restricted expression of 5-HT(2B) receptors in bone marrow cells developed hypoxia or monocrotaline-induced increase in pulmonary pressure and vascular remodeling, whereas restricted elimination of 5-HT(2B) receptors on bone marrow cells confers a complete resistance. Moreover, ex vivo culture of human CD34(+) or mice c-kit(+) progenitor cells in the presence of a 5-HT(2B) receptor antagonist resulted in altered myeloid differentiation potential. Thus, we demonstrate that activation of 5-HT(2B) receptors on bone marrow lineage progenitors is critical for the development of PAH.

Can larger cemented femoral components reduce periprosthetic fractures?

Introduction The risk for late periprosthetic fractures is higher in patients treated for a neck of femur fracture compared to those treated for osteoarthritis. It has been hypothesised that osteopenia and consequent decreased stiffness of the proximal femur are responsible for this. We investigated if a femoral component with a bigger body would increase the torque to failure in a biaxially loaded composite sawbone model. Method A biomechanical composite sawbone model was used. Two different body sizes (Exeter 44-1 vs 44-4) of a polished tapered cemented stem were implanted by an experienced surgeon, in 7 sawbones each and loaded at 40 deg/s internal rotation until failure. Torque to fracture and fracture energy were measured using a biaxial materials testing device (Instron 8874). Data are non-parametric and tested with Mann-Whitney U-test. Results The mean torque load to fracture was 154.1 NM (SD 4.4) for the 44-1 stem and 229 NM (SD10.9) for the 44-4 stem (p = 0.01). The mean fracture energy was 9.6 J (SD1.2) for the 44-1 stem and 17.2 J (SD2.0) for the 44-4 stem (p = 0.14). Conclusion the use of a large body polished tapered cemented stem for neck of femur fractures increases the torque to failure in a biomechanical model and therefore is likely to reduce late periprosthetic fracture risk in this vulnerable cohort.

In-hospital mortality rates after a cemented femoral component for displaced neck of femur fractures

Aim This prospective cohort study investigated whether the use of preoperative anticoagulants is an independent risk factor for the outcomes of surgical treatment of patients with a neck of femur fracture. Methods Data was obtained from a prospectively collected database. All patients admitted for a neck of femur fracture between Nov 2010 and Oct 2011 were included. This resulted in three hundred twenty-eight patients with 330 neck of femur fractures. Four groups were defined; patients preoperatively (i) on aspirin (n = 105); (ii) on clopidogrel (n = 28); (iii) on warfarin (n = 30), and; (iv) without any anticoagulation history (n = 167, the control group). The non-warfarin group included the aspirin group, clopidogrel group and the control group. Primary outcome was the in-hospital mortality. Secondary outcomes were the postoperative complications, return to theatre and length of stay. Results Thirteen in-hospital deaths were identified, 4 deaths in the aspirin group, 1 death in the clopidogrel group, 2 deaths in the warfarin group and 6 deaths in the control group. No significant difference in the mortality rates was found between the different groups. Also in the secondary outcomes, no significant difference was found between the four groups. A trend to a higher wound complication rate for the warfarin group was detected. Conclusion The use of clopidrogel or aspirin pre operatively is not an influence on short term patient outcome for patients with a neck of femur fracture. Surgical procedures should not be delayed to reverse their influence.

Proximal femoral morphology in regions of hard and soft water

This study compared proximal femoral morphology in patients living in soft and hard water regions. The proximal femoral morphology of two groups of 70 patients living in hard and soft water regions with a mean age of 72.3 (range 50 to 87 years) were measured using an antero-posterior radiograph of the non-operated hip with magnification adjusted. The medullary canal diameter at the level of the lesser trochanter (LT) was significantly wider in patients living in the hard water region (mean width 1.9 mm wider; p= 0.003). No statistical significant difference was found in the medullary canal width at 10 cm below the level of LT, Dorr index, or Canal Bone Ratio (CBR). In conclusion, the proximal femoral morphology does differ in patients living in soft and hard water areas. These results may have an important clinical bearing in patients undergoing total hip replacement surgery. Further research is needed to determine whether implant survivorship is affected in patients living in hard and soft water regions.

Human CD141(+) (BDCA-3)(+) dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens

The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141(+) DC subset. CD141(+) DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-beta, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c(+) DC subset. Polyinosine-polycytidylic acid (poly I:C)-activated CD141(+) DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8(+) cytotoxic T lymphocytes than poly I:C-activated CD1c(+) DCs. Importantly, CD141(+) DCs, but not CD1c(+) DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141(+) DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8 alpha(+) DC subset. The data demonstrate a role for CD141(+) DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.

Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

Teachers’ beliefs about the possibilities and limitations of digital games in classrooms

Teachers’ beliefs about what it is (or is not) possible to achieve with digital games in educational contexts will inevitably influence the decisions that they make about how, when, and for what specific purposes they will bring these games into their classrooms. They play a crucial role in both shaping and responding to the complex contextual factors which influence how games are understood and experienced in educational settings. Throughout this article the authors draw upon data collected for a large-scale, mixed-methods research project focusing on literacy, learning and teaching with digital games in Australian classrooms, to focus explicitly on the attitudes,understandings and expectations held about digital games by diverse teachers at the beginning of the project. They seek to identify the beliefs about games that motivated teachers’ participation in a digital games research project while focusing, as well, on concerns that teachers express about risks or limitations of such a project. The authors’ aim is to develop a detailed picture of the mindsets that teachers bring to games-based learning environments, and the relevance of these mindsets to broader debates about the relationship between games, learning and school.

Can larger-bodied cemented femoral components reduce periprosthetic fractures? A biomechanical study

Introduction: The risk for late periprosthetic femoral fractures is higher in patients treated for a neck of femur fracture compared to osteoarthritis. It has been hypothesised that osteopenia and consequent decreased stiffness of the proximal femur are responsible for this. We investigated whether a femoral component with a bigger body would increase the torque to failure in a biaxially loaded composite Sawbone model. Material and methods: A biomechanical bone analogue was used. Two different body sizes (Exeter 44-1 vs 44-4) of a polished tapered cemented femoral stem were implanted by an experienced surgeon in 7 bone analogues each and internally rotated at 40°/s until failure. Torque to fracture and fracture energy were measured using a biaxial materials testing device (Instron 8874, MI, USA). The data were non-parametric and therefore tested with the Mann-Whitney U-test. Results: The median torque to fracture was 156.7 Nm (IQR 19.7) for the 44-1 stem and 237.1 Nm (IQR 52.9) for the 44-4 stem (p=0.001). The median fracture energy was 8.5J (IQR 7.3) for the 44-1 stem and 19.5J (IQR 8.8) for the 44-4 stem (p=0.014). Conclusions: The use of a large body polished tapered cemented stems for neck of femur fractures increases the torque to failure in a biomechanical model and therefore is likely to reduce late periprosthetic fracture risk in this vulnerable cohort.

Effects of anticoagulants on outcome of femoral neck fracture surgery

PURPOSE To review records of 330 patients who underwent surgery for femoral neck fractures with or without preoperative anticoagulation therapy. METHODS Medical records of 235 women and 95 men aged 48 to 103 years (mean, 81.6; standard deviation [SD], 13.1) who underwent surgery for femoral neck fractures with or without preoperative anticoagulation therapy were reviewed. 30 patients were on warfarin, 105 on aspirin, 28 on clopidogrel, and 167 were controls. The latter 3 groups were combined as the non-warfarin group and compared with the warfarin group. Hospital mortality, time from admission to surgery, length of hospital stay, return to theatre, and postoperative complications (wound infection, deep vein thrombosis, and pulmonary embolism) were assessed. RESULTS The warfarin and control groups were significantly younger than the clopidogrel and aspirin groups (80.8 vs. 80.0 vs. 84.2 vs. 83.7 years, respectively, p<0.05). 81% of the patients underwent surgery within 48 hours of admission. The overall mean time from admission to surgery was 1.8 days; it was longer in the warfarin than the aspirin, clopidogrel, and control groups (3.3 vs. 1.8 vs. 1.6 vs. 1.6 days, respectively, p<0.001). The mean length of hospital stay was 17.5 (SD, 9.6; range, 3-54) days. The overall hospital mortality was 3.9%; it was 6.7% in the warfarin group, 3.8% in the aspirin group, 3.6% in the clopidogrel group, and 3.6% in the control group (p=0.80). Four patients returned to theatre for surgery: one in the warfarin group for washout of a haematoma, 2 in the aspirin group for repositioning of a mal-fixation and for debridement of wound infection, and one in the control group for debridement of wound infection. The warfarin group did not differ significantly from non-warfarin group in terms of postoperative complication rate (6.7% vs. 2.7%, p=0.228) and the rate of return to theatre (3.3% vs. 1%, p=0.318). CONCLUSION It is safe to continue aspirin and clopidogrel prior to surgical treatment for femoral neck fracture. The risk of delaying surgery outweighs the peri-operative bleeding risk.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

The relationship between stress, HPA axis functioning and brain structure in first episode psychosis over the first 12 weeks of treatment

Stress and abnormal hypothalamic-pituitary-adrenal axis functioning have been implicated in the early phase of psychosis and may partly explain reported changes in brain structure. This study used magnetic resonance imaging to investigate whether biological measures of stress were related to brain structure at baseline and to structural changes over the first 12 weeks of treatment in first episode patients (n=22) compared with matched healthy controls (n=22). At baseline, no significant group differences in biological measures of stress, cortical thickness or hippocampal volume were observed, but a significantly stronger relationship between baseline levels of cortisol and smaller white matter volumes of the cuneus and anterior cingulate was found in patients compared with controls. Over the first 12 weeks of treatment, patients showed a significant reduction in thickness of the posterior cingulate compared with controls. Patients also showed a significant positive relationship between baseline cortisol and increases in hippocampal volume over time, suggestive of brain swelling in association with psychotic exacerbation, while no such relationship was observed in controls. The current findings provide some support for the involvement of stress mechanisms in the pathophysiology of early psychosis, but the changes are subtle and warrant further investigation.

Anthropogenic nitrogen deposition predicts local grassland primary production worldwide

Humans dominate many important Earth system processes including the nitrogen (N) cycle. Atmospheric N deposition affects fundamental processes such as carbon cycling, climate regulation, and biodiversity, and could result in changes to fundamental Earth system processes such as primary production. Both modelling and experimentation have suggested a role for anthropogenically altered N deposition in increasing productivity, nevertheless, current understanding of the relative strength of N deposition with respect to other controls on production such as edaphic conditions and climate is limited. Here we use an international multiscale data set to show that atmospheric N deposition is positively correlated to aboveground net primary production (ANPP) observed at the 1-m2 level across a wide range of herbaceous ecosystems. N deposition was a better predictor than climatic drivers and local soil conditions, explaining 16% of observed variation in ANPP globally with an increase of 1 kg N·ha-1·yr-1 increasing ANPP by 3%. Soil pH explained 8% of observed variation in ANPP while climatic drivers showed no significant relationship. Our results illustrate that the incorporation of global N deposition patterns in Earth system models are likely to substantially improve estimates of primary production in herbaceous systems. In herbaceous systems across the world, humans appear to be partially driving local ANPP through impacts on the N cycle.

Consistent responses of soil microbial communities to elevated nutrient inputs in grasslands across the globe

Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.